Non-small cell lung cancer (NSCLC) accounts for 85% of all lung cancer cases, and for the most cancer-related deaths. The survival pathway of Akt, its downstream effectors, the mammalian target of rapamycin (mTOR) and ribosomal protein S6 kinase (p70 S6K), and the Ras-extracellular signal-regulated kinase (Erk1/2) pathways are activated in cancer leading to cell survival and growth. Thus, approaches that inhibit these signaling molecules may prove useful in the fight against lung cancer. Exercise is associated with health benefits and a limited number of studies indicate that serum from physically active individuals inhibit mammary and prostate cancer cell growth. In this study, we examined the effects of post exercise serum on proliferation, survival, and signaling cascades of human NSCLC cells. Blood was collected from male subjects prior to, 5 min, 1 h, and 24 h after a single bout of high intensity interval exercise on a cycle ergometer. Exposure of NSCLC cells to post exercise serum resulted in the inhibition of cell proliferation and survival, as well as significant reduction of phosphorylated/activated Akt, mTOR, p70 S6K, and Erk1/2 levels compared to cells treated with serum taken pre-exercise. Our data suggest that post exercise serum has anti-cancer properties in lung cancer and deserves further systematic investigation in animal models.
Cancer is a multifactorial pathology and it represents the second leading cause of death worldwide. In the recent years, numerous studies highlighted the dual role of the gut microbiota in preserving host’s health. Gut resident bacteria are able to produce a number of metabolites and bioproducts necessary to protect host’s and gut’s homeostasis. Conversely, several microbiota subpopulations may expand during pathological dysbiosis and therefore produce high levels of toxins capable, in turn, to trigger both inflammation and tumorigenesis. Importantly, gut microbiota can interact with the host either modulating directly the gut epithelium or the immune system. Numerous gut populating bacteria, called probiotics, have been identified as protective against the genesis of tumors. Given their capability of preserving gut homeostasis, probiotics are currently tested to help to fight dysbiosis in cancer patients subjected to chemotherapy and radiotherapy. Most recently, three independent studies show that specific gut resident species may potentiate the positive outcome of anti-cancer immunotherapy. The highly significant studies, uncovering the tight association between gut microbiota and tumorigenesis, as well as gut microbiota and anti-cancer therapy, are here described. The role of the Lactobacillus rhamnosus GG (LGG), as the most studied probiotic model in cancer, is also reported. Overall, according to the findings here summarized, novel strategies integrating probiotics, such as LGG, with conventional anti-cancer therapies are strongly encouraged.
Cancer tissues are composed of cancer cells and the surrounding stromal cells (e.g., fibroblasts, vascular endothelial cells, and immune cells), in addition to the extracellular matrix. Most studies investigating carcinogenesis and the progression, invasion, metastasis, and angiogenesis of cancer have focused on alterations in cancer cells, including genetic and epigenetic changes. Recently, interactions between cancer cells and the stroma have attracted considerable attention, and increasing evidence has accumulated on this. Several researchers have gradually clarified the origins, features, and roles of cancer-associated fibroblasts (CAFs), a major component of the cancer stroma. CAFs function in a similar manner to myofibroblasts during wound healing. We previously reported the relationship between CAFs and angiogenesis. Interleukin-6 (IL-6), a multifunctional cytokine, plays a central role in regulating inflammatory and immune responses, and important roles in the progression, including proliferation, migration, and angiogenesis, of several cancers. We showed that CAFs are an important IL-6 source and that anti-IL-6 receptor antibody suppressed angiogenesis and inhibited tumor-stroma interactions. Furthermore, CAFs contribute to drug-resistance acquisition in cancer cells. The interaction between cancer cells and the stroma could be a potential target for anti-cancer therapy.
Low invasive tests with high sensitivity for colorectal cancer and advanced precancerous lesions will increase adherence rates, and improve clinical outcomes. We have performed an ultra-performance liquid chromatography/time-of-flight mass spectrometry (UPLC-(TOF) MS)-based metabolomics study to identify faecal biomarkers for the detection of patients with advanced neoplasia. A cohort of 80 patients with advanced neoplasia (40 advanced adenomas and 40 colorectal cancers) and 49 healthy subjects were analysed in the study. We evaluated the faecal levels of 105 metabolites including glycerolipids, glycerophospholipids, sterol lipids and sphingolipids. We found 18 metabolites that were significantly altered in patients with advanced neoplasia compared to controls. The combinations of seven metabolites including ChoE(18:1), ChoE(18:2), ChoE(20:4), PE(16:0/18:1), SM(d18:1/23:0), SM(42:3) and TG(54:1), discriminated advanced neoplasia patients from healthy controls. These seven metabolites were employed to construct a predictive model that provides an area under the curve (AUC) median value of 0.821. The inclusion of faecal haemoglobin concentration in the metabolomics signature improved the predictive model to an AUC of 0.885. In silico gene expression analysis of tumour tissue supports our results and puts the differentially expressed metabolites into biological context, showing that glycerolipids and sphingolipids metabolism and GPI-anchor biosynthesis pathways may play a role in tumour progression.
Cancer is a multifaceted condition, in which a senescent cell begins dividing in an irregular manner due to various factors such as DNA damage, growth factors and inflammation. Inflammation is not typically discussed as carcinogenic; however, a significant percentage of cancers arise from chronic microbial infections and damage brought on by chronic inflammation. A hallmark cancer-inducing microbe isHelicobacter pyloriand its causation of peptic ulcers and potentially gastric cancer. This review discusses the recent developments in understanding microbes in health and disease and their potential role in the progression of cancer. To date, microbes can be linked to almost every cancer, including colon, pancreatic, gastric, and even prostate. We discuss the known mechanisms by which these microbes can induce cancer growth and development and how inflammatory cells may contribute to cancer progression. We also discuss new treatments that target the chronic inflammatory conditions and their associated cancers, and the impact microbes have on treatment success. Finally, we examine common dietary misconceptions in relation to microbes and cancer and how to avoid getting caught up in the misinterpretation and over inflation of the results.
Urothelial cancer of the bladder, renal pelvis, ureter, and other urinary organs is the fifth most common cancer in the United States, and systemic platinum-based chemotherapy remains the standard of care for first-line treatment of advanced/metastatic urothelial carcinoma (UC). Until recently, there were very limited options for patients who are refractory to chemotherapy, or do not tolerate chemotherapy due to toxicities and overall outcomes have remained very poor. While the role of immunotherapy was first established in non-muscle invasive bladder cancer in the 1970s, no systemic immunotherapy was approved for advanced disease until the recent approval of a programmed death ligand-1 (PD-L1) inhibitor, atezolizumab, in patients with advanced/metastatic UC who have progressed on platinum-containing regimens. This represents a significant milestone in this disease after a void of over 30 years. In addition to atezolizumab, a variety of checkpoint inhibitors have shown a significant activity in advanced/metastatic urothelial carcinoma and are expected to gain Food and Drug Administration (FDA) approval in the near future. The introduction of novel immunotherapy agents has led to rapid changes in the field of urothelial carcinoma. Numerous checkpoint inhibitors are being tested alone or in combination in the first and subsequent-line therapies of metastatic disease, as well as neoadjuvant and adjuvant settings. They are also being studied in combination with radiation therapy and for non-muscle invasive bladder cancer refractory to BCG. Furthermore, immunotherapy is being utilized for those ineligible for firstline platinum-based chemotherapy. This review outlines the novel immunotherapy agents which have either been approved, or are currently being investigated in clinical trials in UC.
Bladder cancer is one of the most prevalent cancers worldwide. Unfortunately, there have been few advances in its clinical management due to a poor understanding of the correlations between its molecular and clinical features. Mounting evidence suggests that bladder cancer comprises a group of molecularly heterogeneous diseases that undergo a variety of clinical courses and possess diverse therapeutic responses. Owing to the close association between its molecular subtypes and clinicopathological features, specific therapeutic strategies have recently been suggested. This review summarizes the current understanding of the molecular pathology of bladder cancer, including its molecular biomarkers/pathways and molecular subtypes that have been newly identified using high-throughput technologies. It also discusses advances in our understanding of personalized treatments for specific molecular subtypes.
Integrins are transmembrane receptors that are central to the biology of many human pathologies. Classically mediating cell-extracellular matrix and cell-cell interaction, and with an emerging role as local activators of TGFβ, they influence cancer, fibrosis, thrombosis and inflammation. Their ligand binding and some regulatory sites are extracellular and sensitive to pharmacological intervention, as proven by the clinical success of seven drugs targeting them. The six drugs on the market in 2016 generated revenues of some US$3.5 billion, mainly from inhibitors of α4-series integrins. In this review we examine the current developments in integrin therapeutics, especially in cancer, and comment on the health economic implications of these developments.
The incidence of acute myeloid leukemia (AML) increases with age, but the outcomes for older adults with AML are poor due to underlying tumor biology, poor tolerance to aggressive treatment, and the physiologic changes of aging. Because of the underlying heterogeneity in health status, treatment decisions are difficult in this population. A geriatric assessment (GA) refers to the use of various validated tools to assess domains that are important in older adults including physical function, cognition, comorbidities, polypharmacy, social support, and nutritional status. In older patients with cancer, a GA can guide treatment decision-making, predict treatment toxicity, and guide supportive care interventions. Compared to solids tumors, there is a relative lack of studies evaluating the use of a GA in older patients with AML. In this review, we will discuss the principles, common domains, feasibility, and benefits of GA, with a focus on older patients with AML that includes practical applications for clinical management.
Hematopoietic stem cells (HSCs) maintain an organism’s immune system for a lifetime, and derangements in HSC proliferation and differentiation result in hematologic malignancies. Chronic inflammation plays a contributory if not causal role in HSC dysfunction. Inflammation induces HSC exhaustion, which promotes the emergence of mutant clones that may be resistant to an inflammatory microenvironment; this likely promotes the onset of a myeloid hematologic malignancy. Inflammatory cytokines are characteristically high in patients with myeloid malignancies and are linked to disease initiation, symptom burden, disease progression, and worsened prognostic survival. This review will cover our current understanding of the role of inflammation in the initiation, progression, and complications of myeloid hematologic malignancies, drawing from clinical studies as well as murine models. We will also highlight inflammation as a therapeutic target in hematologic malignancies.