Loss of gap junctional intercellular communication (GJIC) between cancer cells is a common characteristic of malignant transformation. This communication is mediated by connexin proteins that make up the functional units of gap junctions. Connexins are highly regulated at the protein level and phosphorylation events play a key role in their trafficking and degradation. The metastasis suppressor breast cancer metastasis suppressor 1 (BRMS1) upregulates GJIC and decreases phosphoinositide-3-kinase (PI3K) signaling. On the basis of these observations, we set out to determine whether there was a link between PI3K and GJIC in tumorigenic and metastatic cell lines. Treatment of cells with the well-known PI3K inhibitor LY294002, and its structural analogue LY303511, which does not inhibit PI3K, increased homotypic GJIC; however, we found the effect to be independent of PI3K/AKT inhibition. We show in multiple cancer cell lines of varying metastatic capability that GJIC can be restored without enforced expression of a connexin gene. In addition, while levels of connexin 43 remained unchanged, its relocalization from the cytosol to the plasma membrane was observed. Both LY294002 and LY303511 increased the activity of protein kinase A (PKA). Moreover, PKA blockade by the small molecule inhibitor H89 decreased the LY294002/LY303511-mediated increase in GJIC. Collectively, our findings show a connection between PKA activity and GJIC mediated by PI3K-independent mechanisms of LY294002 and LY303511. Manipulation of these signaling pathways could prove useful for antimetastatic therapy.

Interferons (IFNs) are a family of naturally existing glycoproteins known for their antiviral activity and their ability to influence the behavior of normal and transformed cell types. Type I Interferons include IFN-α and IFN-β. Currently, IFN-α has numerous approved antitumor applications, including malignant melanoma, in which IFN-α has been shown to increase relapse free survival. Moreover, IFN-α has been successfully used in the intralesional treatment of cutaneous squamous cell carcinoma (SCC) and basal cell carcinoma (BCC). In spite of these promising clinical results; however, there exists a paucity of knowledge on the precise anti-tumor action of IFN-α/β at the cellular and molecular levels in cutaneous malignancies such as SCC, BCC, and melanoma. This review summarizes current knowledge on the extent to which Type I IFN influences proliferation, apoptosis, angiogenesis, and immune function in normal skin, cutaneous SCC, BCC, and melanoma.

BackgroundThe variety and complexity of dermatologic diseases in Afghanistan and the associated diagnostic resource constraints have not been previously studied. Moreover, the utility of store-and-forward teledermatopathology in this resource-limited setting has not been investigated.MethodsA retrospective analysis was conducted of 150 store-and-forward teledermatopathology cases that were composed of a clinical history, clinical images, and histologic images that were sent from an academic teaching hospital in Kabul to a dermatology-trained dermatopathologist at Emory University in the United States between November 2013 and June 2017. For each case, the histologic impression of the Emory dermatopathologist was compared with that of the Kabul-based general pathologist and the clinical differential diagnosis and histologic impression of the Kabul-based dermatologist.ResultsEighty-one of the cases that were analyzed were from female patients. The diagnosis after telepathology consultation differed from the first entity in the clinical differential diagnosis in 34.7% of cases. The telepathology consultation refined the Afghan general pathologist’s histologic impression 45.5% of the time and the Kabul-based dermatologist’s histologic impression 24.3% of the time. A clinically significant difference in care was made in 19.3% of cases for which an analysis could take place between the histologic impressions of the Emory dermatopathologist and U.S.-trained dermatologist. The most common resource constraints that limited a definitive diagnosis were the inability to perform infectious stains and cultures to identify specific pathogens (19.3% of cases) and immunofluorescence studies to confirm autoimmune bullous disease (6.7% of cases).ConclusionsThese results highlight the important diagnostic role that teledermatopathology can serve in resource-limited settings such as in Afghanistan.

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The bones are the most common sites of breast cancer metastasis. Upon arrival within the bone microenvironment, breast cancer cells coordinate the activities of stromal cells, resulting in an increase in osteoclast activity and bone matrix degradation. In late stages of bone metastasis, breast cancer cells induce apoptosis in osteoblasts, which further exacerbates bone loss. However, in early stages, breast cancer cells induce osteoblasts to secrete inflammatory cytokines purported to drive tumor progression. To more thoroughly evaluate the role of osteoblasts in early stages of breast cancer metastasis to the bones, we used green fluorescent protein-labeled human breast cancer cell lines MDA-MB-231 and MDA-MB-435, which both induce osteolysis after intra-femoral injection in athymic mice, and the murine pre-osteoblastic cell line MC3T3-E1 to modulate osteoblast populations at the sites of breast cancer metastasis. Breast cancer cells were injected directly into the femur with or without equal numbers of MC3T3-E1 cells. Tumors grew significantly larger when co-injected with breast cancer cells and MC3T3-E1 cells than injected with breast cancer cells alone. Osteolysis was induced in both groups, indicating that MC3T3-E1 cells did not block the ability of breast cancer cells to cause bone destruction. MC3T3-E1 cells promoted tumor growth out of the bone into the extraosseous stroma. These data suggest that breast cancer cells and osteoblasts communicate during early stages of bone metastasis and promote tumor growth.

Based on these data, cessation of anticoagulation medication before thyroid FNA is not necessary to obtain sufficient cellular material for diagnosis, thus eliminating the need for procedural delays, patient inconvenience, and risks associated with anticoagulation medication cessation.

Scanner-based protocol-driven ultrasound is an effective method that streamlines image acquisition and significantly improves efficiency in an ultrasound department while ensuring consistency and adherence to accreditation guidelines.

Gap junctional intercellular communication (GJIC) regulates cellular homeostasis by propagating signaling molecules, exchanging cellular metabolites, and coupling electrical signals. In cancer, cells exhibit altered rates of GJIC which may play a role in neoplastic progression. KATP channels help maintain membrane polarity; and, linkages between KATP channel activity and rates of GJIC have been established. The mechanistic relationship has not been fully elucidated. We report the effects of treatment with multiple KATP antagonist compounds on GJIC in metastatic cell lines demonstrating an increase in communication rates following treatment with compounds possessing specificities towards the SUR2 subunit of KATP. These effects remained consistent using cell lines with different expression levels of SUR1 and SUR2, suggesting possible off target effects on GJIC by these compounds.