Neuroendocrine Breast Carcinoma: Interesting Images of an Underdiagnosed Entity.

Breast cancer is the most common type of cancer of the female gender. A rare subtype of breast cancer is the invasive breast carcinoma (IBC) with neuroendocrine (NE) differentiation. Its incident is believed to be 0.1% to 5% of all breast cancers. We report a rare case of a 66-year old woman who presented with an isolated nodule of the left breast. The patient underwent modified radical mastectomy. Pathology revealed invasive breast carcinoma with neuroendocrine differentiation. Invasive breast carcinoma is an extremely rare group of neoplasms, the exact frequency of which cannot be determined with current data. Therefore, it is necessary for future studies to focus on the pathophysiology of this subtype of breast cancer and on the potential therapeutic approaches.

Tumor cell metabolic reprogramming and hypoxic immunosuppression: driving carcinogenesis to metastatic colonization.

A significant factor in the antitumor immune response is the increased metabolic reprogramming of immunological and malignant cells. Increasing data points to the fact that cancer metabolism affects not just cancer signaling, which is essential for maintaining carcinogenesis and survival, but also the expression of immune cells and immune-related factors such as lactate, PGE2, arginine, IDO, which regulate the antitumor immune signaling mechanism. In reality, this energetic interaction between the immune system and the tumor results in metabolic competition in the tumor ecosystem, limiting the amount of nutrients available and causing microenvironmental acidosis, which impairs the ability of immune cells to operate. More intriguingly, different types of immune cells use metabolic reprogramming to keep the body and self in a state of homeostasis. The process of immune cell proliferation, differentiation, and performance of effector functions, which is crucial to the immune response, are currently being linked to metabolic reprogramming. Here, we cover the regulation of the antitumor immune response by metabolic reprogramming in cancer cells and immune cells as well as potential strategies for metabolic pathway targeting in the context of anticancer immunotherapy. We also discuss prospective immunotherapy-metabolic intervention combinations that might be utilized to maximize the effectiveness of current immunotherapy regimes.

Immunohistochemical Femoral Nerve Study Following Bisphosphonates Administration.

Background and objectives: Bisphosphonates represent selective inhibitors of excess osteoblastic bone resorption that characterizes all osteopathies, targeting osteoclasts and their precursors. Their long-term administration in postmenopausal women suffering from osteoporosis has resulted in neural adverse effects. The current study focuses on the research of possible alterations in the femoral nerve, caused by bisphosphonates. We hypothesized that bisphosphonates, taken orally (per os), may produce degenerative changes to the femoral nerve, affecting lower-limb posture and walking neuronal commands. Materials and Methods: In order to support our hypothesis, femoral nerve specimens were extracted from ten female 12-month-old Wistar rats given 0.05 milligrams (mg) per kilogram (kg) of body weight (b.w.) per week alendronate per os for 13 weeks and from ten female 12-month-old Wistar rats given normal saline that were used as a control group. Specimens were studied using immunohistochemistry for selected antibodies NeuN (Neuronal Nuclear Protein), a protein located within mature, postmitotic neural nucleus, and cytosol and Sox10 (Sex-determining Region Y (SRY) - High-Motility Group (HMG) - box 10). The latter marker is fundamental for myelination of peripheral nerves. Obtained slides were examined under a light microscope. Results: Samples extracted from rats given alendronate were more Sox10 positive compared to samples of the control group, where the marker's expression was not so intense. Both groups were equally NeuN positive. Our results are in agreement with previous studies conducted under a transmission electron microscope. Conclusions: The suggested pathophysiological mechanism linked to histological alterations described above is possibly related to toxic drug effects on Schwann and neuronal cells. Our hypothesis enhances the existing scientific evidence of degenerative changes present on femoral nerve following bisphosphonates administration, indicating a possible relationship between alendronate use and neuronal function.

Potential drug-drug interactions in prescriptions dispensed in community pharmacies in Greece.

OBJECTIVES: To evaluate the nature, type and prevalence of potential drug-drug interactions (DDIs) in prescriptions dispensed in community pharmacies in Thessaloniki, Greece. Secondary objectives included the classification of DDIs as per pharmacotherapeutic class of the medications and the investigation of the relationship between medical specialties and the frequency of potential DDIs, as well as the relationship between DDIs and prescription size. Setting DDIs are a common cause of adverse drug reactions (ADRs) among patients using multiple drug therapy. In Greece a reliable computerized surveillance system for monitoring potential DDIs is not yet fully established. As a result, the prevalence of such DDIs in prescriptions dispensed by community pharmacies in Greece is unknown. METHODS: We conducted a prospective, descriptive study. Over a 3-month period (November 2007-January 2008), a total of 1,553 handwritten prescriptions were collected from three community pharmacies in Thessaloniki, Greece. The prescriptions were processed using the Drug Interactions Checker within the www.drugs.com database. The identified potential DDIs were categorized into two classes, major and moderate, according to their level of clinical significance. MAIN OUTCOME MEASURES: Overall 213 prescriptions had one or more potential DDIs and a total of 287 major and moderate DDIs were identified. Potential DDIs were identified in 18.5% of all prescriptions. Major DDIs were identified in 1.9% of all prescriptions and represented 10.5% of all DDIs detected, whereas moderate DDIs were identified in 16.6% of all prescriptions and represented 89.5% of all DDIs detected. The rate of DDIs increased with prescription size. The most common drug involved in major DDIs was amiodarone which interacts with potassium-wasting diuretics, digoxin, simvastatin and acenocoumarol. CONCLUSIONS: Our results indicate that patients in Greece are at risk of ADRs caused by medications due to potential DDIs. An appropriate surveillance system for monitoring such interactions should be implemented and physicians should be more aware of potentially harmful DDIs. Pharmacists can contribute to the detection and prevention of drug-related injuries, especially of clinically meaningful DDIs that pose a potential risk to patient safety.