Altered Endoplasmic Reticulum Calcium Pump Expression during Breast Tumorigenesis

Endoplasmic reticulum calcium homeostasis is involved in several essential cell functions including cell proliferation, protein synthesis, stress responses or secretion. Calcium uptake into the endoplasmic reticulum is performed by Sarco/Endoplasmic Reticulum Calcium ATPases (SERCA enzymes). In order to study endoplasmic reticulum calcium homeostasis in situ in mammary tissue, in this work SERCA3 expression was investigated in normal breast and in its benign and malignant lesions in function of the cell type, degree of malignancy, and histological and molecular parameters of the tumors. Our data indicate, that although normal breast acinar epithelial cells express SERCA3 abundantly, its expression is strongly decreased already in very early non-malignant epithelial lesions such as adenosis, and remains low in lobular carcinomas. Whereas normal duct epithelium expresses significant amounts of SERCA3, its expression is decreased in several benign ductal lesions, as well as in ductal adenocarcinoma. The loss of SERCA3 expression is correlated with Elston-Ellis grade, negative hormone receptor expression or triple negative status in ductal carcinomas. The concordance between decreased SERCA3 expression and several histological, as well as molecular markers of ductal carcinogenesis indicates that endoplasmic reticulum calcium homeostasis is remodeled during tumorigenesis in the breast epithelium

Discussing Challenges in Diagnosis of Tuberculous Meningitis and Neurosarcoidosis.

Isolated chronic granulomatous meningitis remains a diagnostic challenge for the physician. Symptoms are often nonspecific and ancillary tests have low-sensitivity rates, which may delay targeted treatment and lead to increased morbidity and mortality. Here, we discuss the challenges in diagnosing and treating patients with chronic meningitis by reporting two cases of previously healthy patients who presented with granulomatous meningitis on brain biopsy

Histone deacetylase inhibitor- and PMA-induced upregulation of PMCA4b enhances Ca2+ clearance from MCF-7 breast cancer cells

The expression of the plasma membrane Ca2+ ATPase (PMCA) isoforms is altered in several types of cancer cells suggesting that they are involved in cancer progression. In this study we induced differentiation of MCF-7 breast cancer cells by histone deacetylase inhibitors (HDACis) such as short chain fatty acids (SCFAs) or suberoylanilide hydroxamic acid (SAHA), and by phorbol 12-myristate 13-acetate (PMA) and found strong upregulation of PMCA4b protein expression in response to these treatments. Furthermore, combination of HDACis with PMA augmented cell differentiation and further enhanced PMCA4b expression both at mRNA and protein levels. Immunocytochemical analysis revealed that the upregulated protein was located mostly in the plasma membrane. To examine the functional consequences of elevated PMCA4b expression, the characteristics of intracellular Ca2+ signals were investigated before and after differentiation inducing treatments, and also in cells overexpressing PMCA4b. The increased PMCA4b expression – either by treatment or overexpression – led to enhanced Ca2+ clearance from the stimulated cells. We found pronounced PMCA4 protein expression in normal breast tissue samples highlighting the importance of this pump for the maintenance of mammary epithelial Ca2+ homeostasis. These results suggest that modulation of Ca2+ signaling by enhanced PMCA4b expression may contribute to normal development of breast epithelium and may be lost in cancer

A severe case of neuroleukemiosis caused by B cell chronic lymphocytic leukemia, presenting as mononeuritis multiplex.

To report an exceptional case of nerve infiltration by an otherwise benign chronic B cell leukemia, inducing severe mononeuritis multiplex. The patient underwent extensive evaluation, including nerve conduction study and myography, brain and plexus MRI, and nerve biopsy. The clinical and electrophysiological diagnosis was a mononeuritis multiplex with severe motor and sensory involvement; only the nerve biopsy allowed definite diagnosis and introduction of chemotherapy, leading to resolution of sensory deficit and progressive motor improvement. Neuroleukemiosis caused by chronic lymphoid leukemia is an exceptional diagnosis. The presence of other possible causes like cryoglobulinemia could induce avoidance of nerve biopsy thus undertreating patient, since steroid treatment is not expected to be efficient on lymphocytic proliferation. Our case stretches the importance of nerve biopsy and raises neuromuscular specialist's awareness of this rare entity

Modulation of B-cell endoplasmic reticulum calcium homeostasis by Epstein-Barr virus Latent Membrane Protein-1

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Microfluidic-based immunohistochemistry for breast cancer diagnosis: a comparative clinical study.

Breast cancer is a highly heterogeneous disease. The efficacy of tailored therapeutic strategies relies on the precise detection of diagnostic biomarkers by immunohistochemistry (IHC). Therefore, considering the increasing incidence of breast cancer cases, a concomitantly time-efficient and accurate diagnosis is clinically highly relevant. Microfluidics is a promising innovative technology in the field of tissue diagnostic, enabling for rapid, reliable, and automated immunostaining. We previously reported the microfluidic-based HER2 (human epidermal growth factor receptor 2) detection in breast carcinomas to greatly correlate with the HER2 gene amplification level. Here, we aimed to develop a panel of microfluidic-based IHC protocols for prognostic and therapeutic markers routinely assessed for breast cancer diagnosis, namely HER2, estrogen/progesterone receptor (ER/PR), and Ki67 proliferation factor. The microfluidic IHC protocol for each marker was optimized to reach high staining quality comparable to the standard procedure, while concomitantly shortening the staining time to 16 min-excluding deparaffinization and antigen retrieval step-with a turnaround time reduction up to 7 folds. Comparison of the diagnostic score on 50 formaldehyde-fixed paraffin-embedded breast tumor resections by microfluidic versus standard staining showed high concordance (overall agreement: HER2 94%, ER 95.9%, PR 93.6%, Ki67 93.7%) and strong correlation (ρ coefficient: ER 0.89, PR 0.88, Ki67 0.87; p < 0.0001) for all the analyzed markers. Importantly, HER2 genetic reflex test for all discordant cases confirmed the scores obtained by the microfluidic technique. Overall, the microfluidic-based IHC represents a clinically validated equivalent approach to the standard chromogenic staining for rapid, accurate, and automated breast cancer diagnosis

An exceptional presentation of pituicytoma apoplexy: A case report.

Pituicytomas are a rare form of indolent neoplasms, which typically present with visual disturbance and hypopituitarism. Complete resection by a trans-sphenoidal approach is the optimal treatment. Only 80 cases have been described thus far in the current literature and the present case is the first to describe the development of pituitary apoplexy in the context of a pituicytoma. A 77-year-old man presented with fatigue and clinical signs of hypogonadism and a sellar lesion was diagnosed at cerebral magnetic resonance imaging (MRI). A watch-and-wait management was initially decided and 1 year after the initial diagnosis, he presented with a thunderclap headache with images suggestive of pituitary apoplexy. A pituitary adenoma was suspected and an endoscopic resection was decided upon the development of a visual deficit. Pathological analysis established the correct diagnosis of a pituicytoma. Pituicytomas are characterised by dense vascularisation, thus ischaemic and haemorrhagic events may be common. When confronted with a hypervascularised pituitary lesion demonstrating strong contrast enhancement and no abnormal hormonal secretion, one must maintain a high index of suspicion for a pituicytoma. A wide range of differential diagnoses should thus be considered in the context of pituitary apoplexy

Bacillus cereus bacteremia with central nervous system involvement: A neuropathological study.

<i>Bacillus cereus</i> is a widely-distributed, gram-positive or variable, rod-shaped bacterium frequently considered a contaminant in clinical specimens. It is recognized as a potential pathogen inducing self-limiting emetic or diarrheal food poisoning or localized infection in immunocompetent patients. True <italic>B. cereus</italic> bacteremia is uncommon and mainly observed in fragile patients, notably in immunocompromised individuals. We report clinical, radiological, and pathological findings of a 64-year-old patient with a history of acute myeloid leukemia who initially presented a fever while neutropenic after the induction of a second cycle of chemotherapy. He developed <italic>B. cereus</italic> bacteremia with invasive infection and a fatal outcome. The clinical and radiological data of this case are compared to a previously-published series of 21 patients from our institution with <italic>B. cereus</italic> bacteremia. This study highlights the clinical challenge to diagnose <italic>B. cereus</italic> and the importance of the delay between the detection of <italic>B. cereus</italic> and the initiation of an effective targeted antibiotic therapy. This case presented an aggressive evolution with multiple necrotic and hemorrhagic foci in the brain. Upon histological examination, <italic>B. cereus</italic> virulence was notably reflected by the dissection of blood vessel walls by the bacilli and luminal occlusion, a pattern that has not been yet reported.