Intratumoral CXCL12 Gradients Contextualize Tumor Cell Invasion, Migration and Immune Suppression in Breast Cancer.

Although the CXCL12/CXCR4 pathway has been prior investigated for its prometastatic and immuno- suppressive roles in the tumor microenvironment, evidence on the spatiotemporal regulation of these hallmarks has been lacking. Here, we demonstrate that CXCL12 forms a gradient specifically around cancer cell intravasation doorways, also known as Tumor Microenvironment of Metastasis (TMEM) doorways, thus facilitating the chemotactic translocation of prometastatic tumor cells expressing CXCR4 toward the perivascular TMEM doorways for subsequent entry into peripheral circulation. Fur- thermore, we demonstrate that the CXCL12-rich micro-environment around TMEM doorways may cre- ate immunosuppressive niches, whereby CD8 T cells, despite being attracted to these regions, often exhibit reduced effector functions, limiting their efficacy.

Advancing Brain Research through Surface-Enhanced Raman Spectroscopy (SERS): Current Applications and Future Prospects.

Surface-enhanced Raman spectroscopy (SERS) has recently emerged as a potent analytical technique with significant potential in the field of brain research. This review explores the applications and innovations of SERS in understanding the pathophysiological basis and diagnosis of brain disorders. SERS holds significant advantages over conventional Raman spectroscopy, particularly in terms of sensitivity and stability.

Uncovering potential diagnostic and pathophysiological roles of α-synuclein and DJ-1 in melanoma.

Background: Melanoma, the most lethal skin cancer type, occurs more frequently in Parkinson's disease (PD), and PD is more frequent in melanoma patients, suggesting disease mechanisms overlap. α-synuclein, a protein that accumulates in PD brain, and the oncogene DJ-1, which is associated with PD autosomal recessive forms, are both elevated in melanoma cells. Whether this indicates melanoma progression or constitutes a protective response remains unclear.

An emerging paradigm of CXCL12 involvement in the metastatic cascade.

The chemokine CXCL12, also known as stromal cell-derived factor 1 (SDF1), has emerged as a pivotal regulator in the intricate molecular networks driving cancer progression. As an influential factor in the tumor microenvironment, CXCL12 plays a multifaceted role that spans beyond its traditional role as a chemokine inducing invasion and metastasis. Indeed, CXCL12 has been assigned functions related to epithelial-to-mesenchymal transition, cancer cell stemness, angiogenesis, and immunosuppression, all of which are currently viewed as specialized biological programs contributing to the "metastatic cascade" among other cancer hallmarks.

Glycosylation spectral signatures for glioma grade discrimination using Raman spectroscopy.

Background: Gliomas are the most common brain tumours with the high-grade glioblastoma representing the most aggressive and lethal form. Currently, there is a lack of specific glioma biomarkers that would aid tumour subtyping and minimally invasive early diagnosis. Aberrant glycosylation is an important post-translational modification in cancer and is implicated in glioma progression.

The diagnostic and prognostic potential of the EGFR/MUC4/MMP9 axis in glioma patients.

Glioblastoma is the most aggressive form of brain cancer, presenting poor prognosis despite current advances in treatment. There is therefore an urgent need for novel biomarkers and therapeutic targets. Interactions between mucin 4 (MUC4) and the epidermal growth factor receptor (EGFR) are involved in carcinogenesis, and may lead to matrix metalloproteinase-9 (MMP9) overexpression, exacerbating cancer cell invasiveness.

Mucin 13 (MUC13) as a candidate biomarker for ovarian cancer detection: potential to complement CA125 in detecting non-serous subtypes.

Objectives: Ovarian cancer is the most lethal gynecological malignancy in developed countries. One of the key associations with the high mortality rate is diagnosis at late stages. This clinical limitation is primarily due to a lack of distinct symptoms and detection at the early stages.

Emerging Roles of Immune Cells in Cancer Development and Progression.

Immune cells are a major constituent of the tumor microenvironment, and participate in interactions with tumor cells to promote the acquisition of critical hallmarks of cancer [...

Transcriptome profiling and proteomic validation reveals targets of the androgen receptor signaling in the BT-474 breast cancer cell line.

Background: Accumulating evidence suggests that the androgen receptor (AR) and its endogenous ligands influence disease progression in breast cancer (BCa). However, AR-mediated changes in BCa differ among the various BCa subtypes according to their hormone receptor profile [i.e.

Message in the bottle: regulation of the tumor microenvironment via exosome-driven proteolysis.

Exosomes comprise a subtype of extracellular vesicles involved in cell-to-cell communication, specifically by transporting biological molecules, such as proteins and nucleic acids, to either local or more distant recipient cells, thus triggering distinct biological behaviors. Included in the exosome cargo is frequently a wide range of proteolytic enzymes, such as the matrix metalloproteinases (MMPs), the disintegrin and metalloproteinases (ADAMs), and the ADAM with thrombospondin-like motifs (ADAMTSs), whose functions contribute to the development and progression of cancer. In recent years, extensive research on the potential use of exosomes in diagnostic and therapeutic applications for personalized medicine has emerged, but the targeting of the proteolytic cargo of exosomes has not been fully exploited in this direction.

Systems biology reveals key tissue-specific metabolic and transcriptional signatures involved in the response of plant genotypes to salt stress.

Salt stress is an important factor limiting plant productivity by affecting plant physiology and metabolism. To explore salt tolerance adaptive mechanisms in the model legume we used three genotypes with differential salt-sensitivity: TN6.18 (highly sensitive), Jemalong A17 (moderately sensitive), and TN1.

The Cancer Cell Dissemination Machinery as an Immunosuppressive Niche: A New Obstacle Towards the Era of Cancer Immunotherapy.

Although cancer immunotherapy has resulted in unpreceded survival benefits to subsets of oncology patients, accumulating evidence from preclinical animal models suggests that the immunosuppressive tumor microenvironment remains a detrimental factor limiting benefit for many patient subgroups. Recent efforts on lymphocyte-mediated immunotherapies are primarily focused on eliminating cancer foci at primary and metastatic sites, but few studies have investigated the impact of these therapies on the highly complex process of cancer cell dissemination. The metastatic cascade involves the directional streaming of invasive/migratory tumor cells toward specialized blood vessel intravasation gateways, called TMEM doorways, to the peripheral circulation.

Involvement of Polyamine Metabolism in the Response of Genotypes to Salt Stress.

Salinity constitutes one of the most important causes leading to severe reduction in plant yield. Several reports correlate the accumulation of polyamines in plants with tolerance to abiotic stress cues. The present study examined three genotypes with differing sensitivities to salinity (TN1.

Cancer and Parkinson's Disease: Common Targets, Emerging Hopes.

Cancer and neurodegeneration are two major leading causes of morbidity and death worldwide. At first sight, the two fields do not seem to share much in common and, if anything, might be placed on opposite ends of a spectrum. Although neurodegeneration results in excessive neuronal cell death, cancer emerges from increased proliferation and resistance to cell death.

Extracellular proteolysis in glioblastoma progression and therapeutics.

Gliomas encompass highly invasive primary central nervous system (CNS) tumours of glial cell origin with an often-poor clinical prognosis. Of all gliomas, glioblastoma is the most aggressive form of primary brain cancer. Current treatments in glioblastoma are insufficient due to the invasive nature of brain tumour cells, which typically results in local tumour recurrence following treatment.

The Contribution of Race to Breast Tumor Microenvironment Composition and Disease Progression.

Breast cancer is the second most commonly diagnosed cancer in American women following skin cancer. Despite overall decrease in breast cancer mortality due to advances in treatment and earlier screening, black patients continue to have 40% higher risk of breast cancer related death compared to white patients. This disparity in outcome persists even when controlled for access to care and stage at presentation and has been attributed to differences in tumor subtypes or gene expression profiles.

Liraglutide: New Perspectives for the Treatment of Polycystic Ovary Syndrome.

Polycystic ovary syndrome is a complex and heterogenous disorder involving multiple organ systems and different molecular pathways. It is tightly associated with obesity and especially abdominal obesity. As body weight reduction is the main modifiable risk factor for polycystic ovary syndrome, therapeutic approaches in overweight or obese women with polycystic ovary syndrome have been developed.

Kallikrein-related peptidases protein expression in lymphoid tissues suggests potential implications in immune response.

Objectives: Kallikrein-related peptidases (KLKs) are a subgroup of 15 secreted chymotrypsin- and trypsin-like serine proteases that have been reported to possess novel functions in innate immunity and inflammation. Since the potential role of KLKs in immunity has not been studied in detail at the protein level, we examined the expression pattern of 12 members of the KLK family in immune-related tissues.

Design & Methods: Protein expression in tissue extracts was evaluated using immunoassays (ELISA).

Midkine (MDK) growth factor: a key player in cancer progression and a promising therapeutic target.

Midkine is a heparin-binding growth factor, originally reported as the product of a retinoic acid-responsive gene during embryogenesis, but currently viewed as a multifaceted factor contributing to both normal tissue homeostasis and disease development. Midkine is abnormally expressed at high levels in various human malignancies and acts as a mediator for the acquisition of critical hallmarks of cancer, including cell growth, survival, metastasis, migration, and angiogenesis. Several studies have investigated the role of midkine as a cancer biomarker for the detection, prognosis, and management of cancer, as well as for monitoring the response to cancer treatment.

Screening of chemical libraries in pursuit of kallikrein-5 specific inhibitors for the treatment of inflammatory dermatoses.

Background Aberrant kallikrein activity is observed in a number of inflammatory dermatoses. Up-regulation of kallikrein-5 (KLK5) activity leads to uncontrolled skin desquamation and cleavage of proteinase-activated receptor-2 (PAR2), causing the release of pro-inflammatory cytokines and disruption of epidermal barrier function. This study aimed to identify KLK5-specific small molecule inhibitors which can serve as the foundation of a novel therapeutic for inflammatory skin disorders.

Species Pervasiveness Within the Group of Coagulase-Negative Staphylococci Associated With Meat Fermentation Is Modulated by pH.

During spontaneous meat fermentations, , , and are generally the most prevailing species within the communities of coagulase-negative staphylococci (CNS). There is an interest to introduce CNS isolates from artisan-style spontaneous meat fermentations as starter cultures in more industrialized processes, as to confer additional quality benefits. However, staphylococcal competitiveness within the meat matrix is affected by the processing conditions, which vary considerably among product types.

Effect of temperature and pH on the community dynamics of coagulase-negative staphylococci during spontaneous meat fermentation in a model system.

Coagulase-negative staphylococci (CNS) contribute to the product quality of fermented meats. In spontaneously fermented meats, CNS communities are variable and difficult to predict, as their compositions depend on a superposed combination of different processing factors. To partially disentangle this superposition, a meat model system was used to study the influence of temperature and pH on the CNS community dynamics.

Expression profile of human tissue kallikrein 15 provides preliminary insights into its roles in the prostate and testis.

Background: Human tissue kallikrein 15 (KLK15) is the latest member of the kallikrein-related peptidase family. Little is known about the pathophysiological roles of KLK15. Previous studies implied a role of KLK15 in prostate cancer.