Tumor-derived extracellular vesicles convey solute transporters to induce bioenergetic dependence shift contributing to treatment resistance.

Growing evidence points to the tumor microenvironment's role in developing drug resistance. A key element of this microenvironment is inter-cellular communication, which includes the release of membrane-encapsulated vesicles containing various cargo, known as extracellular vesicles (EVs). Understanding how EVs contribute to acquired resistance holds significant clinical implications.

Impact of CD151 overexpression on prognosis and therapy in non-small cell lung cancer patients lacking EGFR mutations.

This study investigates CD151, a protein linked to cancer progression, in non-small cell lung cancer (NSCLC) patients without epidermal growth factor receptor (EGFR) mutations. These patients often have limited treatment options. The study used retrospective analysis to examine 157 adenocarcinoma biopsy specimens and 199 patient cases from The Cancer Genome Atlas, correlating CD151 expression with patient survival.

Hyperphosphorylation of BCL-2 family proteins underlies functional resistance to venetoclax in lymphoid malignancies.

The B cell leukemia/lymphoma 2 (BCL-2) inhibitor venetoclax is effective in chronic lymphocytic leukemia (CLL); however, resistance may develop over time. Other lymphoid malignancies such as diffuse large B cell lymphoma (DLBCL) are frequently intrinsically resistant to venetoclax. Although genomic resistance mechanisms such as BCL2 mutations have been described, this probably only explains a subset of resistant cases.

FAM3C in circulating tumor-derived extracellular vesicles promotes non-small cell lung cancer growth in secondary sites.

: Metastasis is a complex process with a molecular underpinning that remains unclear. We hypothesize that cargo proteins conducted by extracellular vesicles (EVs) released from tumors may confer growth and metastasis potential on recipient cells. Here, we report that a cytokine-like secreted protein, FAM3C, contributes to late-stage lung tumor progression.

Targeting Metabolism in Cancer Cells and the Tumour Microenvironment for Cancer Therapy.

Targeting altered tumour metabolism is an emerging therapeutic strategy for cancer treatment. The metabolic reprogramming that accompanies the development of malignancy creates targetable differences between cancer cells and normal cells, which may be exploited for therapy. There is also emerging evidence regarding the role of stromal components, creating an intricate metabolic network consisting of cancer cells, cancer-associated fibroblasts, endothelial cells, immune cells, and cancer stem cells.

Integration of Antiangiogenic Therapy with Cisplatin and Gemcitabine Chemotherapy in Patients with Nasopharyngeal Carcinoma.

Purpose: Induction cisplatin and gemcitabine chemotherapy is a standard treatment for locally advanced nasopharyngeal carcinoma (NPC). Inhibition of VEGF axis has been shown to promote maturation of microvasculature and improve perfusion. We conducted a four-arm study to assess the effect of two doses of either sunitinib or bevacizumab with chemotherapy in NPC.

A common MET polymorphism harnesses HER2 signaling to drive aggressive squamous cell carcinoma.

c-MET receptors are activated in cancers through genomic events like tyrosine kinase domain mutations, juxtamembrane splicing mutation and amplified copy numbers, which can be inhibited by c-MET small molecule inhibitors. Here, we discover that the most common polymorphism known to affect MET gene (N375S), involving the semaphorin domain, confers exquisite binding affinity for HER2 and enables MET to interact with HER2 in a ligand-independent fashion. The resultant MET/HER2 dimer transduces potent proliferative, pro-invasive and pro-metastatic cues through the HER2 signaling axis to drive aggressive squamous cell carcinomas of the head and neck (HNSCC) and lung (LUSC), and is associated with poor prognosis.

Targeting Cell Metabolism as Cancer Therapy.

Cancer cells exhibit altered metabolic pathways to keep up with biosynthetic and reductionoxidation needs during tumor proliferation and metastasis. The common induction of metabolic pathways during cancer progression, regardless of cancer histio- or genotype, makes cancer metabolism an attractive target for therapeutic exploitation. Emerging data suggest that these altered pathways may even result in resistance to anticancer therapies.

Microfluidic-Based Immunomodulation of Immune Cells Using Upconversion Nanoparticles in Simulated Blood Vessel-Tumor System.

The goal of cancer immunotherapy is the selective killing of malignant cells by the cooperated efforts of immune cells at the primary and secondary sites. Here, we developed folic acid and secondary lymphoid tissue chemokine-loaded mesoporous silica-modified upconversion nanoparticle construct as a targeting, delivery, and imaging system to attract immune cells to folate receptor-expressing tumor cells. The effectiveness of the nanoparticles in targeting dendritic cells and T cells to the tumor compartment was tested in a vasculature-tumor interface model constructed from the co-culture of endothelial cells and ovarian cancer cells, in different interconnected channels in a microfluidic device.

SPHK1 regulates proliferation and survival responses in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is characterized by unique aggressive behavior and lack of targeted therapies. Among the various molecular subtypes of breast cancer, it was observed that TNBCs express elevated levels of sphingosine kinase 1 (SPHK1) compared to other breast tumor subtypes. High levels of SPHK1 gene expression correlated with poor overall and progression- free survival, as well as poor response to Doxorubicin-based treatment.

Reed-Sternberg cell-derived lymphotoxin-α activates endothelial cells to enhance T-cell recruitment in classical Hodgkin lymphoma.

It is known that cells within the inflammatory background in classical Hodgkin lymphoma (cHL) provide signals essential for the continual survival of the neoplastic Hodgkin and Reed-Sternberg (HRS) cells. However, the mechanisms underlying the recruitment of this inflammatory infiltrate into the involved lymph nodes are less well understood. In this study, we show in vitro that HRS cells secrete lymphotoxin-α (LTα) which acts on endothelial cells to upregulate the expression of adhesion molecules that are important for T cell recruitment.

Intracellular trafficking and endocytosis of CXCR4 in fetal mesenchymal stem/stromal cells.

Background: Fetal mesenchymal stem/stromal cells (MSC) represent a developmentally-advantageous cell type with translational potential.To enhance adult MSC migration, studies have focussed on the role of the chemokine receptor CXCR4 and its ligand SDF-1 (CXCL12), but more recent work implicates an intricate system of CXCR4 receptor dimerization, intracellular localization, multiple ligands, splice variants and nuclear accumulation. We investigated the intracellular localization of CXCR4 in fetal bone marrow-derived MSC and role of intracellular trafficking in CXCR4 surface expression and function.

PDK1 signaling toward PLK1-MYC activation confers oncogenic transformation, tumor-initiating cell activation, and resistance to mTOR-targeted therapy.

Unlabelled: Although 3-phosphoinositide-dependent protein kinase-1 (PDK1) has been predominately linked to the phosphoinositide 3-kinase (PI3K)-AKT pathway, it may also evoke additional signaling outputs to promote tumorigenesis. Here, we report that PDK1 directly induces phosphorylation of Polo-like kinase 1 (PLK1), which in turn induces MYC phosphorylation and protein accumulation. We show that PDK1-PLK1-MYC signaling is critical for cancer cell growth and survival, and small-molecule inhibition of PDK1/PLK1 provides an effective approach for therapeutic targeting of MYC dependency.

Targeting CCL21-folic acid-upconversion nanoparticles conjugates to folate receptor-α expressing tumor cells in an endothelial-tumor cell bilayer model.

The ability of some malignant cells to evade immunosurveillance has been a major contribution to the inability of the host's immune system to eradicate the neoplastic cells. This has led to the development of various immunological strategies to augment the host immune response as part of cancer treatment. In this study, we developed folic acid (FA)/secondary lymphoid tissue chemokine (CCL21)/upconversion fluorescent nanoparticles (UCNs) conjugates as a targeting and delivery system to attract immune cells to folate receptor (FR) expressing tumor cells.

Gelsolin induces colorectal tumor cell invasion via modulation of the urokinase-type plasminogen activator cascade.

Gelsolin is a cytoskeletal protein which participates in actin filament dynamics and promotes cell motility and plasticity. Although initially regarded as a tumor suppressor, gelsolin expression in certain tumors correlates with poor prognosis and therapy-resistance. In vitro, gelsolin has anti-apoptotic and pro-migratory functions and is critical for invasion of some types of tumor cells.

B55β-associated PP2A complex controls PDK1-directed myc signaling and modulates rapamycin sensitivity in colorectal cancer.

The PP2A serine/threonine protein phosphatase serves as a critical cellular regulator of cell growth, proliferation, and survival. However, how this pathway is altered in human cancer to confer growth advantage is largely unknown. Here, we show that PPP2R2B, encoding the B55β regulatory subunit of the PP2A complex, is epigenetically inactivated by DNA hypermethylation in colorectal cancer.

Palladin, an actin-associated protein, is required for adherens junction formation and intercellular adhesion in HCT116 colorectal cancer cells.

Palladin is a scaffold protein involved in the formation of actin-associated protein complexes. Gene expression array analysis on the poorly metastatic HCT116 colon cancer cell line and a metastatic derivative cell line (E1) with EMT (epithelial-mesenchymal transition) features showed a down-regulation of palladin gene expression in the latter. Knockdown of palladin expression in the HCT116 cells suppressed junctional localization of E-cadherin, reduced intercellular adhesion and collective cell migration, showing that palladin plays an important role in maintaining the integrity of adherens junctions.

Immunogenic potential of Enterococcus faecalis biofilm under simulated growth conditions.

Introduction: The aim of this study was to evaluate the effect of growth modes (planktonic and biofilms) of Enterococcus faecalis on the intracellular survival and ability to produce tumor necrosis factor alpha (TNF-alpha) and interleukin (IL)-6 after interacting with monocytes/in vitro-differentiated macrophages.

Methods: In vitro biofilms of three E. faecalis strains (ATCC-29212, OG1RF, and FA2-2) were grown on dentin under simulated nutrient-rich and nutrient-deprived conditions.

Suppression of host innate immune response by Burkholderia pseudomallei through the virulence factor TssM.

Burkholderia pseudomallei is a Gram-negative saprophyte that is the causative agent of melioidosis, a severe infectious disease endemic in Northern Australia and Southeast Asia. This organism has sparked much scientific interest in the West because of its classification as a potential bioterrorism agent by the U.S.

Coadministration of the fungal immunomodulatory protein FIP-Fve and a tumour-associated antigen enhanced antitumour immunity.

Fve is a fungal protein isolated from the golden needle mushroom Flammulina velutipes and has previously been reported to trigger immunological responses in both mouse and human lymphocytes. In this study, we evaluated the potential application of Fve as an adjuvant for tumour immunotherapy and examined the underlying mechanism(s). When the human papillomavirus (HPV)-16 E7 oncoprotein was used as a model antigen, mice coimmunized with HPV-16 E7 and Fve showed enhanced production of HPV-16 E7-specific antibodies as well as expansion of HPV-16 E7-specific interferon (IFN)-gamma-producing CD4(+) and CD8(+) T cells as compared with mice immunized with HPV-16 E7 alone.

The 130-kDa glycoform of CD43 functions as an E-selectin ligand for activated Th1 cells in vitro and in delayed-type hypersensitivity reactions in vivo.

Selectins are carbohydrate-binding molecules involved in constitutive lymphocyte homing and chronic and acute inflammation processes. Th1 lymphocytes participate in cell-mediated inflammatory reactions, where the selectins play a role and predominate in delayed-type hypersensitivity (DTH) reactions of the skin. Of the many candidate ligands for selectins, only P-selectin glycoprotein ligand 1 (PSGL-1), which also acts as an E-selectin ligand, has been characterized extensively at molecular, cellular, and functional levels on T cells.

Continuing education for pathology laboratory technologists: a needs analysis in a Singapore teaching hospital.

Background/aims: Continuing education is important to laboratory technologists. It helps them keep pace with the advances in medicine and pathology and thus to provide quality service. A survey was conducted to assess the attitudes of pathology laboratory technologists towards different educational activities.