Notes

TRPC3, an overlooked, general pacemaker route?
We previously identified estrogen-responsive finger protein (Efp) as an estrogen-induced gene, and showed that the positive immunoreactivity of Efp is a poor prognostic factor for patients with breast cancer. We also demonstrated that Efp has distinctive roles in innate immunity by activating pattern recognition receptor retinoic acid-inducible gene I (RIG-I). The clinical value of RIG-I protein expression in breast cancer had not been evaluated in relationship with patients' prognosis.

Tissue samples of estrogen receptor-positive invasive breast cancer were obtained from 145 female patients with breast cancer who underwent surgical treatment. Immunoreactivities of RIG-I and Efp were analyzed with the antibodies generated for the present study.

Positive immunoreactivity of RIG-I was correlated with lower disease-free survival (P= .032) and was an independent poor prognostic factor (P= .043). RIG-I immunoreactivity was positively correlated with that of Efp (P= .0004). Patients with positive immunoreactivities of both RIG-I and Efp proteins were associated with a lower disease-free survival rate (P= .005).

Positive immunoreactivity of RIG-I has clinical significance as a poor prognostic factor in patients with estrogen receptor-positive breast cancer. A positive correlation of RIG-I and Efp immunoreactivities was observed, and the combination of their immunoreactivities can be used to predict patients' prognosis.
Positive immunoreactivity of RIG-I has clinical significance as a poor prognostic factor in patients with estrogen receptor-positive breast cancer. A positive correlation of RIG-I and Efp immunoreactivities was observed, and the combination of their immunoreactivities can be used to predict patients' prognosis.
The American Joint Committee on Cancer (AJCC) staging system is the reference standard for describing the extent of neoplastic disease on the basis of the size of primary tumor (T), and the presence of regional lymph node (N) involvement and distant metastasis (M). Multiple foci of invasive breast carcinoma may pose staging challenges to the reporting pathologist. We set out to evaluate the practice of local breast pathologists with regard to staging of multiple foci of invasive carcinoma.

Breast pathologists were surveyed at a Community of Interest in Breast Pathology meeting. The live voting survey contained 6 case-based scenarios of multiple foci of invasive mammary carcinoma of the same or different histologic type and with unilateral or bilateral involvement. A supporting illustration was provided for each case.

There was poor interobserver agreement with no consensus reached among the respondents in any of the cases. Staging choices varied from staging tumors together irrespective of histology or procedure type to staging tumors of the same histologic type together, or staging each tumor focus separately. Confusion was particularly evident when tumor foci with different histologic types were present.

Inconsistencies exist in the reporting of AJCC pathologic TNM stage for multiple foci of invasive carcinoma. The results serve as a reminder that education and strict adherence to the AJCC guidelines is essential for establishing standard practice in order to provide accurate cancer staging and ensure optimal clinical management.
Inconsistencies exist in the reporting of AJCC pathologic TNM stage for multiple foci of invasive carcinoma. The results serve as a reminder that education and strict adherence to the AJCC guidelines is essential for establishing standard practice in order to provide accurate cancer staging and ensure optimal clinical management.A growing number of studies are pointing out the need for a conceptual shift from a brain-centered to a body-inclusive approach in mental health research. In this perspective, the link between the immune and the nervous system, which are deeply interconnected and continuously interacting, is one of the most important novel theoretical framework to investigate the biological bases of major depressive disorder and, more in general, mental illness. Indeed, depressed patients show high levels of inflammatory markers, administration of pro-inflammatory drugs triggers a depressive symptomatology and antidepressant efficacy is reduced by excessive immune system activation. A number of molecular and cellular mechanisms have been hypothesized to act as a link between the immune and brain function, thus representing potential pharmacologically targetable processes for the development of novel and effective therapeutic strategies. These include the modulation of the kynurenine pathway, the crosstalk between metabolic and inflammatory processes, the imbalance in acquired immune responses, in particular T cell responses, and the interplay between neural plasticity and immune system activation. In the personalized medicine approach, the assessment and regulation of these processes have the potential to lead, respectively, to novel diagnostic approaches for the prediction of treatment outcome according to the patient's immunological profile, and to improved efficacy of antidepressant compounds through immune modulation.Congenital lower urinary tract disorders are a family of diseases affecting both urinary storage and voiding as well as upstream kidney function. Current treatments include surgical reconstruction but many children still fail to achieve urethral continence or progress to chronic kidney disease. New therapies can only be achieved through undertaking research studies to enhance our understanding of congenital lower urinary tract disorders. Animal models form a critical component of this research, a corner of the triangle composed of human in-vitro studies and clinical research. We describe the current animal models for two rare congenital bladder disorders, posterior urethral valves (PUV) and bladder exstrophy (BE). AS1517499 in vivo We highlight important areas for researchers to consider when deciding which animal model to use to address particular research questions and outline the strengths and weaknesses of current models available for PUV and BE. Finally, we present ideas for refining animal models for PUV and BE in the future to stimulate future researchers and help them formulate their thinking when working in this field.
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