Cancer Metastasis

Orchestrated modulation of cell adhesion is essential for development and homeostasis in multicellular organisms. It optimizes embedding of the cell in its dynamic environment and facilitates appropriate cell responses and intercellular communication. Chronic disturbance of this delicate equilibrium causes defects in tissue architecture and sometimes cancer. In tumor cell biology, dynamic control of adhesion molecules is important to proceed through the metastatic cascade and to allow cell release from the primary tumor, invasion of the surrounding matrix, intravasation and adhesion to vascular endothelial cells to facilitate extravasation. Intertwined and multiple adhesive interactions rather than individual interactions presumably play critical roles in neoplastic development. Yet, knowledge of the contribution of each individual adhesion molecule is essential to unravel this network of interactions. This review will focus on activated leukocyte cell adhesion molecule (ALCAM/CD166) and its role in human melanoma progression. It is hypothesized that ALCAM may function as a cell surface sensor to register local growth saturation and to regulate cellular signaling and dynamic responses.

In spite of great progress in therapeutic practices over the past decade, neither the incidence nor the deaths from cancer have changed over the past thirty years. Existing anticancer drugs have limited efficacy, severe complications, and high costs expensive. Hence, identifying pharmaceutical agents lacking these disadvantages is required. Curcumin (diferuloylmethane), bioactive phenolic component of turmeric derived from the curcuma longa linn rhizome, is such a factor that over the past three to four decades extensive in vitro and in vivo studies have shown it to have anti-cancer, antiviral, anti amyloid, antioxidant, and anti-inflammatory properties. The underlying mechanisms of these effects are various and seem to include different molecular targets, such as transcription factors, growth factors, inflammatory cytokines, protein kinases, enzymes, and the like. This paper reviews modulated molecular-targets of curcumin and its signaling paths. Moreover, in the status quo, a numb...

The elevation of tissue pO 2 induced by hyperbaric oxygen (HBO) is a physiological stimulus that elicits a variety of cellular responses. These effects are largely mediated by, or in response to, an increase in the production of reactive oxygen and nitrogen species (RONS). The major consequences of elevated RONS include increased oxidative stress and enhanced antioxidant capacity, and modulation of redox-sensitive cell signaling pathways. Interestingly, these phenomena underlie both the therapeutic and potentially toxic effects of HBO. Emerging evidence indicates that supporting mitochondrial health is a potential method of enhancing the therapeutic efficacy of, and preventing oxygen toxicity during, HBO. This review will focus on the cellular consequences of HBO, and explore how these processes mediate a delicate balance of cellular protection versus damage.

Almost 25 centuries ago, Hippocrates, the father of medicine, proclaimed "Let food be thy medicine and medicine be thy food." Exploring the association between diet and health continues today. For example, we now know that as many as 35% of all cancers can be prevented by dietary changes. Carcinogenesis is a multistep process involving the transformation, survival, proliferation, invasion, angiogenesis, and metastasis of the tumor and may take up to 30 years. The pathways associated with this process have been linked to chronic inflammation, a major mediator of tumor progression. The human body consists of about 13 trillion cells, almost all of which are turned over within 100 days, indicating that 70,000 cells undergo apoptosis every minute. Thus, apoptosis/cell death is a normal physiological process, and it is rare that a lack of apoptosis kills the patient. Almost 90% of all deaths due to cancer are linked to metastasis of the tumor. How our diet can prevent cancer is the focus of this review. Specifically, we will discuss how nutraceuticals, such as allicin, apigenin, berberine, butein, caffeic acid, capsaicin, catechin gallate, celastrol, curcumin, epigallocatechin gallate, fisetin, flavopiridol, gambogic acid, genistein, plumbagin, quercetin, resveratrol, sanguinarine, silibinin, sulforaphane, taxol, γ-tocotrienol, and zerumbone, derived from spices, legumes, fruits, nuts, and vegetables, can modulate inflammatory pathways and thus affect the survival, proliferation, invasion, angiogenesis, and metastasis of the tumor. Various cell signaling pathways that are modulated by these agents will also be discussed.

Carcinogenesis is a multi-step process which could be prevented by phytochemicals. Phytochemicals from dietary plants and other plant sources such as herbs are becoming increasingly important sources of anticancer drugs or compounds for cancer chemoprevention or adjuvant chemotherapy. Phytochemicals can prevent cancer initiation, promotion, and progression by exerting anti-inflammatory and antioxidative stress effects which are mediated by integrated Nrf2, NF-κB, and AP-1 signaling pathways. In addition, phytochemicals from herbal medicinal plants and/or some dietary plants developed in recent years have been shown to induce apoptosis in cancer cells and inhibition of tumor growth in vivo. In advanced tumors, a series of changes involving critical signaling molecules that would drive tumor cells undergoing epithelial-mesenchymal transition and becoming invasive. In this review, we will discuss the potential molecular targets and signaling pathways that mediate tumor onset and metastasis. In addition, we will shed light on some of the phytochemicals that are capable of targeting these signaling pathways which would make them potentially applicable to cancer chemoprevention, treatment and control of cancer progression.

There is a need in prostate cancer diagnostics and research for a label-free imaging methodology that is nondestructive, rapid, objective, and uninfluenced by water. Raman spectroscopy provides a molecular signature, which can be scaled from micron-level regions of interest in cells to macroscopic areas of tissue. It can be used for applications ranging from in vivo or in vitro diagnostics to basic science laboratory testing. This work describes the fundamentals of Raman spectroscopy and complementary techniques including surface enhanced Raman scattering, resonance Raman spectroscopy, coherent anti-Stokes Raman spectroscopy, confocal Raman spectroscopy, stimulated Raman scattering, and spatially offset Raman spectroscopy. Clinical applications of Raman spectroscopy to prostate cancer will be discussed, including screening, biopsy, margin assessment, and monitoring of treatment efficacy. Laboratory applications including cell identification, culture monitoring, therapeutics development, and live imaging of cellular processes are discussed. Potential future avenues of research are described, with emphasis on multiplexing Raman spectroscopy with other modalities.

El tumor testicular de células germinales es la neoplasia sólida maligna más común en varones entre los 15 y 30 años 2 , a pesar de ser un tumor de pacientes jóvenes este tiene una tasa de curación de hasta el 95%, según su tipo histológico. El tumor primario de células germinales se debe a una trasformación maligna de las células germinales primordiales, estas constituyen el 95% de todas las neoplasias gonadales, su localización no es exclusiva a los testículos, también se puede encontrar en otras partes del cuerpo como retroperitoneo, el mediastino e incluso la hipófisis.

In the course of its development, a neoplasm submits to a very important number of pathological processes leading to the loss of some functions, and gaining others, usually changes that reinforce invasion capacity, immunoresistance and metabolism level adjustments (immortalization). Along with the local invasive ability, cancers can invade new territories far away from the primary site in a phenomenon called metastasis. Its pathophysiology, mechanisms, and consequences are the subject of this discussion.

Chemotherapy or radiotherapy could induce various tumor cell death modalities, releasing tumorderived antigen as well as danger signals that could either be captured for triggering antitumor immune response or ignored. Exploring the interplay among therapeutic drugs, tumor cell death and the immune cells should improve diagnostic, prognostic, predictive, and therapeutic management of tumor. We summarized some of the cell deathderived danger signals and the mechanism for host to sense and response to cell death in the tumor microenvironment. Based on the recent clinical or experimental findings, several strategies have been suggested to improve the immunogenicity of cell death and augment antitumor immunity.

Lymphatic spread if one of the most important prognostic factors in gynecological cancers. Therefore, nodal staging is an essential part of cancer diagnosis and treatment planning. The sentinel lymph node (SLN) is the first lymph node to receive lymphatic fluid from the tumor and is at greatest risk of metastasis. According to the SLN concept, with locating and retrieving the SLN for analysis it is possible to predict the stage of the regional lymph nodes in relation to cancer metastasis without extensive surgical procedures.

Activated Leukocyte Cell Adhesion Molecule (ALCAM/CD166), is expressed on osteoblasts (OB) and hematopoietic stem cells (HSC) residing in the hematopoietic niche, and may have important regulatory roles in bone formation. Because HSC numbers are reduced 77% in CD166(-/-) mice, we hypothesized that changes in bone phenotype and consequently the endosteal niche may partially be responsible for this alteration. Therefore, we investigated bone phenotype and OB function in CD166(-/-) mice. Although osteoclastic measures were not affected by loss of CD166, CD166(-/-) mice exhibited a modest increase in trabecular bone fraction (42%), and increases in osteoid deposition (72%), OB number (60%), and bone formation rate (152%). Cortical bone geometry was altered in CD166(-/-) mice resulting in up to 81% and 49% increases in stiffness and ultimate force, respectively. CD166(-/-) OB displayed elevated alkaline phosphatase (ALP) activity and mineralization, and increased mRNA expression of Fra 1...

The metabolism of arachidonic acid through lipoxygenase pathways leads to the generation of various biologically active eicosanoids. The expression of these enzymes vary throughout the progression of various cancers, and thereby they have been shown to regulate aspects of tumor development. Substantial evidence supports a functional role for lipoxygenase-catalyzed arachidonic and linoleic acid metabolism in cancer development. Pharmacologic and natural inhibitors of lipoxygenases have been shown to suppress carcinogenesis and tumor growth in a number of experimental models. Signaling of hydro[peroxy] fatty acids following arachidonic or linoleic acid metabolism potentially effect diverse biological phenomenon regulating processes such as cell growth, cell survival, angiogenesis, cell invasion, metastatic potential and immunomodulation. However, the effects of distinct LOX isoforms differ considerably with respect to their effects on both the individual mechanisms described and the tumor being examined. 5-LOX and platelet type 12-LOX are generally considered procarcinogenic, with the role of 15-LOX-1 remaining controversial, while 15-LOX-2 suppresses carcinogenesis. In this review, we focus on the molecular mechanisms regulated by LOX metabolism in some of the major cancers. We discuss the effects of LOXs on tumor cell proliferation, their roles in cell cycle control and cell death induction, effects on angiogenesis, migration and the immune response, as well as the signal transduction pathways involved in these processes. Understanding the molecular mechanisms underlying the anti-tumor effect of specific, or general, LOX inhibitors may lead to the design of biologically and pharmacologically targeted therapeutic strategies inhibiting LOX isoforms and/or their biologically active metabolites, that may ultimately prove useful in the treatment of cancer, either alone or in combination with conventional therapies.

Novel approaches toward understanding the evolution of disease can lead to the discovery of biomarkers that will enable better management of disease progression and improve prognostic evaluation. Raman spectroscopy is a promising investigative and diagnostic tool that can assist in uncovering the molecular basis of disease and provide objective, quantifiable molecular information for diagnosis and treatment evaluation. This technique probes molecular vibrations/rotations associated with chemical bonds in a sample to obtain information on molecular structure, composition, and intermolecular interactions. Raman scattering occurs when light interacts with a molecular vibration/rotation and a change in polarizability takes place during molecular motion. This results in light being scattered at an optical frequency shifted (up or down) from the incident light. By monitoring the intensity profile of the inelastically scattered light as a function of frequency, the unique spectroscopic fingerprint of a tissue sample is obtained. Since each sample has a unique composition, the spectroscopic profile arising from Raman-active functional groups of nucleic acids, proteins, lipids, and carbohydrates allows for the evaluation, characterization, and discrimination of tissue type. This review provides an overview of the theory of Raman spectroscopy, instrumentation used for measurement, and variation of Raman spectroscopic techniques for clinical applications in cancer, including detection of brain, ovarian, breast, prostate, and pancreatic cancers and circulating tumor cells.

Pulmonary metastasectomy is an established treatment that can provide improved long-term survival for patients with metastatic tumor(s) in the lung. In this chapter, we discuss the stateof-the-art thoracic surgery in surgical management of lung metastases. The principles of pulmonary metastasectomy, followed by a comparison between thoracotomy and mini-invasive surgery are presented. Different surgical indications, and oncological outcomes according to the surgical approach (open vs mini-invasive), histological types and the number of metastatic nodules in the lung are discussed. Finally, the role of surgical margin, lymphadenectomy, and Note to the Reader: This chapter is part of the book Metastasis (ISBN: 978-0-6453320-2-5), scheduled for publication in April 2022. The book is being published by Exon Publications,

Garbha is the union of shukra and shonita, it is also called as shadbhavatmak garbha, i.e made up of matruja, pitruja, rasaja, satmyja, aatmyaja and satvaja Bhava. All soft organs are included in matruja bhava, hence we can consider Stana as matruja bhava. In this study,316 cases of breast cancer were staudied with respect to maternal and paternal history of breast cancer in which 81.8% cases have positive maternal history. Therefore with this it can be said that Stana is considered as matruja bhava.

This article reviews the current knowledge and experimental research about the mechanisms by which fatty acids and their derivatives control specific gene expression involved during carcinogenesis. Changes in dietary fatty acids, specifically the polyunsaturated fatty acids (PUFAs) of the ω-3 and ω-6 families and some derived eicosanoids from lipoxygenases (LOXs), cyclooxygenases (COXs), and cytochrome P-450 (CYP-450), seem to control the activity of transcription factor families involved in cancer cell proliferation or cell death. Their regulation may be carried out either through direct binding to DNA as peroxisome proliferator-activated receptors (PPARs) or via modulation in an indirect manner of signaling pathway molecules (e.g., protein kinase C [PKC]) and other transcription factors (nuclear factor kappa B [NFκB] and sterol regulatory element binding protein [SREBP]). Knowledge of the mechanisms by which fatty acids control specific gene expression may identify important risk factors for cancer, and provide insight into the development of new therapeutic strategies for a better management of whole-body lipid metabolism.

Fear is a number of chain reactions in the brain that occurs when one encounters a potentially harmful stimulus. The amygdala is the part of the brain that receives information from many parts of the brain and interprets this information to generate the emotion of fear. When the amygdala generates a fear emotion, it transmits impulses to the hypothalamus. The hypothalamus then sends impulses to many numbers of different parts of the body to trigger a fight-or-flight response. Fear hormones are secreted by the adrenal gland. The effect of adrenaline (epinephrine) is increasing heart rate, hypocapnia and declines blood flow to the brain. The effect of cortisol is increasing blood glucose levels by converting stored glycogen and fats into blood sugar. It also suppresses the immune system and causes inflammation. The prime cause of cancer is increasing the amounts of ROS in healthy cells. The aim of this review is to show the effect of chronic fear on the cause of cancer in humans by reviewing related clinical studies and biochemistry of fear and cancer. The role of fear, adrenaline and cortisol in causing the hypoxia in tissues is mentioned in this article.

Photodynamic therapy (PDT) has emerged as a promising alternative to conventional cancer therapies such as surgery, chemotherapy, and radiotherapy. PDT comprises the administration of a photosensitizer, its accumulation in tumor tissue, and subsequent irradiation of the photosensitizer-loaded tumor, leading to the localized photoproduction of reactive oxygen species (ROS). The resulting oxidative damage ultimately culminates in tumor cell death, vascular shutdown, induction of an antitumor immune response, and the consequent destruction of the tumor. However, the ROS produced by PDT also triggers a stress response that, as part of a cell survival mechanism, helps cancer cells to cope with the PDT-induced oxidative stress and cell damage. These survival pathways are mediated by the transcription factors activator protein 1 (AP-1), nuclear factor E2-related factor 2 (NRF2), hypoxia-inducible factor 1 (HIF-1), nuclear factor κB (NF-κB), and those that mediate the proteotoxic stress res...

Colorectal cancer is one of the most common solid tumors affecting people around the world. A significant proportion of patients with colorectal cancer will develop or will present with liver metastases. In some of these patients, the liver is the only site of metastatic disease. Thus, surgical treatment approaches are an appropriate and important treatment option in patients with liver-only colorectal cancer metastases. Resection of colorectal cancer liver metastases can produce long-term survival in selected patients, but the efficacy of liver resection as a solitary treatment is limited by two factors. First, a minority of patients with liver metastases have resectable disease. Second, the majority of patients who undergo successful liver resection for colorectal cancer metastases develop recurrent disease in the liver, extrahepatic sites, or both. In this paper, in addition to the results of liver resection for colorectal cancer metastases, we will review the results of thermal ablation. Each of these surgical treatment modalities can produce long-term survival in a subset of patients with liver-only colorectal cancer metastases, whereas administration of systemic or regional chemotherapy rarely results in long-term survival in these patients. While surgical treatments provide the best chance for long-term survival or, in some cases, the best palliation in patients with colorectal cancer liver metastases, it is clear that further improvements in patient outcome will require multimodality therapy regimens. Modern surgical treatment of colorectal liver metastases can be performed safely with low mortality and transfusion rates, and surgical treatment should be considered in patients with disease confined to their liver.

Mast cells (MC) are a bone marrow-derived, long-lived, heterogeneous cellular population that function both as positive and negative regulators of immune responses. They are arguably the most productive chemical factory in the body and influence other cells through both soluble mediators and cell-to-cell interaction. MC are commonly seen in various tumors and have been attributed alternatively with tumor rejection or tumor promotion.

Cancer progression is a polygenic procedure in which the exosomes can function as substantial roles. Exosomes are tiny, phospholipid bilayer membrane nanovesicles of endocytic derivation with a diameter of 40–100 nm. These nanovesicles can transport bioactive molecules containing mRNAs, proteins, DNA fragments, and non-coding RNAs from a donor cell to recipient cells, and cause the alteration in genetic and epigenetic factors and reprogramming of the target cells. Many diverse cell types such as mesenchymal cells, immune cells, and cancer cells can induce the release of exosomes. Increasing evidence illustrated that the exosomes derived from tumor cells might trigger the tumor initiation, tumor cell growth and progression, metastasis, and drug resistance. The secreted nanovesicles of exosomes can play significant roles in cells communicate via shuttling the nucleic acid molecules and proteins to target cells and tissues. In this review, we discussed multiple mechanisms related to biogenesis, load, and shuttle of the exosomes. Also, we illustrated the diverse roles of exosomes in several types of human cancer development, tumor immunology, angiogenesis, and metastasis. The exosomes may act as the promising biomarkers for the prognosis of various types of cancers which suggested a new pathway for anti-tumor therapeutic of these nanovesicles and promoted exosome-based cancer for clinical diagnostic and remedial procedures.

A major topic covered at the First International Symposium on Cancer Metastasis and the Lymphovascular System was the molecular mechanisms of metastasis. This has become of major interest in recent years as we have discovered new metastasis-related genes and gained understanding of the molecular events of lymphatic metastasis. The symposium covered new aspects and important questions related to the events of metastasis in both humans and * Presented as Session animals. The basic and clinical related research covered in this topic represented many disciplines. The presentations showed novel findings and at the same time, raised many new unanswered questions, indicating the limited knowledge we still have regarding the molecular events of metastasis. The hope is that further unraveling of the direct and indirect molecular events of lymphatic metastasis will lead to new approaches in developing effective therapeutics.

Plasma membrane voltage-sensitive ion channels classically have been associated with a variety of inherited diseases or "channelopathies" that range in the severity of symptoms from mild to lethal. Ion channels are found throughout the body and are responsible for facilitated diffusion of ions down the electrochemical gradient across cells membranes in various tissues. Voltage-sensitive ion channels open in response to changes in the membrane potential and are primarily found in excitable cells and tissues. Potassium, calcium, and sodium channels play critical roles in the development of major diseases, such as hyperkalemia, epilepsy, congenital myotonia and several cardiac arrythmias. Recently, cancer studies have begun to define the role of voltage-sensitive ion channels in the progression of cancer to a more malignant phenotype. In cancer, the increased expression or increased kinetics of voltage-sensitive ion channels is associated with an increasing malignant potential as evinced by their role in cell proliferation, migration and survival; as such, these channels are becoming the targets of significant drug development efforts to block or reduce voltage-sensitive ion channel activity in order to prevent or combat malignant disease. Keywords Neoplasia. Ion channel. Voltage-sensitive. Prostate Abbreviations RT-PCR reverse transcription polymerase chain reaction K v or VGKC voltage-gated potassium channel Na v or VSSC voltage-sensitive sodium channel Ca v or VSCC voltage-sensitive calcium channel 1 Introduction Cancer is the cause of 25% of deaths in the United States [1]. It is estimated that 1,399,790 new cases of cancer will be diagnosed and 564,830 deaths will occur from cancer in 2006 [1]. Two thirds of these deaths will result from complications as a result of cancer metastases/disease progression. Recent studies have demonstrated that voltage-sensitive ion channels play a role in the onset, proliferation and malignant progression of various types of cancer, such as prostate, colon, and glioma [2-5] (Fig. 1). A variety of techniques have been used to determine the function of voltagesensitive ion channels in cancer migration, invasiveness, and metastasis. These studies utilized ion channel agonists and antagonists to manipulate the functional state of the channel in cells to determine the effects of channel activity on cancer cell behavior. Our laboratories are in the process of synthesizing and testing potent, selective, voltagesensitive ion channel (VSIC) antagonists for use as tumoristatic or tumoricidal agents [2, 6].

The present work substantiates the atavistic hypothesis of cancer and considers that cancer initiation starts from a mitotic- blocked precursor cell (protoprecur-sor) that escape death by a process of polyploidisation/ depolyploidisation analogous to the encystment/ excystment process of invasive pathogenic amoebae. The protoprecursor cell down regulates its multicelular genes, up regulating unicellular gene networks of the dark genome; it primes a carcinogenic immortal self sufficient stem and progenitor cell lineage (caSPCL) developed and controlled by basic mechanisms of the common eukaryotic ancestor. The primitive cancer life cycle contains reproductive cyst-like structures (aCLS, PGCCs) protected by a more or less characteristic envelope. aCLS’s microcell progeny forms an atavistic stem cell line capable to convert in two antagonistic sublines: one is the neotic more hypoxic aCLS+ progenitor subline that differentiates multiple generations of reproductive aCLSs by asymmetric cell division, and the other is the more oxygenic vegetative/ somatic aCLS-/siCLS+ subline that do not form aCLSs in cultures however, may express differentiation potential in conditions of stress and genotoxic insults forming stress induced siCLS respectively gCLS. In primitive eukaryotes such as invasive, pathogenic amoebae, progenitor sublines for cycling encystment may transdifferentiate to further vegetative/ somatic sublines; vegetative sublines and clones may change the genotype. We redefine neosis as the atavistic reproductive life cycle of cancer that forms microcells (aCLS progeny) capable of stemness and caSPCL renewal. The aCLS+ subline is the neotic/carcinogenic subline: it generates the atavistic family of stem and progenitor cells (aCSCs). 

Keywords:  cancer, neosis, atavistic stemness, primitive cell lineages, Entamoeba, genotoxic agents, DNA repair

Background: Gastrointestinal neuroendocrine tumors (GI-NETs) are potentially malignant tumors, and their most common location of metastasis is the liver. Objectives: In this report, we will describe our experience with some clinical and pathologic findings of hepatic metastasis in a group of cases of GI-NETs at the largest referral center of GI and liver diseases in south Iran. Materials and Methods: In this four-year study (2011-2014), all GI and liver NETs were extracted from the pathology files of hospitals affiliated with Shiraz University of Medical Sciences. After classification based on the world health organization guidelines, the patients were evaluated according to their location, sex, age, and proliferative index. After studying the imaging and clinical charts of liver-NET cases with an unknown primary location, a complete panel of immunohistochemical markers (TTF-1, CDX-2, CK-7, CK-2, etc.) was used to find the primary GI location. Carcinoid tumors from other sites, such as the lung, were omitted from this study. Results: The most common primary site of metastatic GI-NET to the liver in our center was the small intestine, which was also the most frequent location of GI-NET without liver metastasis. No cases of appendiceal-NET were found with liver metastasis. In 8 cases (11.6%) with liver-NETs, no primary location was identified. GI-NETs with liver metastasis had a significantly higher grade and proliferative index compared with NETs without liver metastasis. Conclusions: Liver metastasis of neuroendocrine tumors in Iran presents in a very similar manner as that seen in western countries. In about 89% of cases with liver-NET, complete imaging, clinical, and pathological studies can help to identify the primary origin of the liver-NET, which is very important in the patient's management.

DNA methylation as part of the epigenetic genesilencing complex is a universal occurring change in lung cancer. Numerous studies investigated methylation of specific genes in primary tumors, in serum or plasma samples, and in specimens from the aerodigestive tract epithelium of lung cancer patients. In most studies, single genes or small numbers of genes were analyzed. Moreover, it has been observed that methylation of certain genes can already be detected in samples from the upper aerodigestive tract epithelium of cancer-free heavy smokers. These findings indicated that methylation of certain genes may be a useful biomarker for prognosis, disease recurrence, early detection, and lung cancer risk assessment. So far, several genes were identified which seem to be of worse prognostic relevance when they were found to be methylated. In addition, it has been shown that a panel of markers may be relevant to predict disease recurrence after surgery. In comparison to analysis of single or small numbers of genes, methods for genome-wide detection of methylation were developed recently. These approaches are focused on either pharmacological re-activation of methylated genes followed by expression microarray analysis or on microarray analysis of sodium bisulfite-treated or affinityenriched methylated DNA sequences. With currently available methods for the simultaneous detection of methylation, up to 28,000 CpG islands can be analyzed. Overall, we are just at the beginning of translating these findings into the clinic and there is hope that future patients will benefit from these results.

BACKGROUND: Lung adenocarcinoma (LADCA) patients with epidermal growth factor receptor (EGFR) mutations are in general associated with relatively high clinical response rate to EGFR-tyrosine kinase inhibitors (TKIs) but not all responded to TKI. It has therefore become important to identify the additional surrogate markers regarding EGFR-TKI sensitivity. METHODS: We first examined the effects of EGFR-TKIs, gefitinib and erlotinib, upon cell proliferation of lung adenocarcinoma cell lines. We then evaluated the gene profiles related to EGFR-TKI sensitivity using a microarray analysis. Results of microarray analysis led us to focus on carcinoembryonic antigen-related cell adhesion molecule (CEACAM) family, CEACAM 3, 5, 6, 7, and 19, as potential further surrogate markers of EGFR-TKI sensitivity. We then examined the correlation between the status of CEACAM 3, 5, 6, 7, and 19 immunoreactivity in LADCA and clinicopathological parameters of individual cases. RESULTS: In the cases with EGFR mutations, the status of all CEACAMs examined was significantly higher than that in EGFR wild-type patients, but there were no significant differences in the status of CEACAMs between TKI responder and nonresponder among 22 patients who received gefitinib therapy. However, among 115 EGFR mutation-negative LADCA patients, both CEACAM6 and CEACAM3 were significantly associated with adverse clinical outcome (CEACAM6) and better clinical outcome (CEACAM3). CONCLUSION: CEACAMs examined in this study could be related to the presence of EGFR mutation in adenocarcinoma cells but not represent the effective surrogate marker of EGFR-TKI in LADCA patients. However, immunohistochemical evaluation of CEACAM3/6 in LADCA patients could provide important information on their clinical outcome.

Membrane-type 1 matrix metalloproteinase (MT1-MMP) is an integral membrane proteinase that is frequently expressed in malignant cancer cells and has potent invasion-promoting activity. When expressed on the cell surface, MT1-MMP degrades the extracellular matrix (ECM) barrier adjacent to the cells to maintain the migration route to traverse the tissue. But MT1-MMP is not just an enzyme that degrades ECM. MT1-MMP also introduces limited cleavage into proteins at the cell-ECM interspaces and converts their functions. The target molecules are ECM components, cell adhesion molecules, and latent forms of MMPs. Through these processing events MT1-MMP modulates the migratory and invasive behavior of the cells.

Dear Sir/Madam

We are currently hosting the Oncologist & Diagnostics Conference  which is going to be organized during August 28-30, 2017 Brussels, Belgium. With great pride and honour, we would like to invite you to participate in Oncologist & Diagnostics Conference in Brussels, Belgium

Kindly let me know about you interest toward participation as a Keynote, Speaker, Poster presentation, E-Poster and Video Presentation, delegate.
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Celina Crystal
Manager of oncology and conferences
P 702 508 5200 Ext 8033
#cancerdiagnostics@cancersummit.org

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ConferenceSeries Ltd invites all the participants across the globe to attend the Oncologist & Diagnostics Conference slated on August 28-30, 2017 at Brussels, Belgium.

Cancer Diagnostics 2017 directs towards addressing main issues as well as future strategies of Cancer. This is going to be the largest and most promising international conference where the program includes Clinical Oncologists, Registered Nurses, Nurse practitioners and the entire medical team involved in patient care, researchers, professional, early career individuals and patient advocates who wish to learn principles of tumor immunology and immunotherapy well as decision makers will come to discuss and debate on various aspects of the challenges, risks and investment opportunities throughout the complete information of Cancers. Cancer Diagnostics 2017 will also provide the three days of discussions on methods and strategies related to management and quality improvement of Diagnostics device developing and Cancer Research and as well as to explore the new ideas and concepts on global scale and the topics include lung cancer, breast cancer, bone cancer, leukemia, blood cancer, cervical cancer, colon-rectum cancer, pediatric cancer, surgical cancer, Prostate cancer, thyroid cancer.

According to 2012 statistics approximately 14.1 million cases are reported and 8.2 million deaths are reported. Lung, Liver, Stomach and bowel cancers cause the most common deaths among the worldwide that accounts nearly half of all the cancer deaths. About 70% increase in the cases are to be expected over the next 2 decades. In males 5 most common sites of cancer are diagnosed in 2012 were lung, prostate, colorectal and liver cancers. In females 5 most common sites diagnosed were breast, colorectal, cervix, lung and stomach cancer. Nearly 60% of the world’s total new cases occur in the Africa, Asia and Central and South America regions. All over the world Denmark ranks 1st in the cancer deaths USA is accompanied next to it.

ConferenceSeries Ltd  which is comprised of 3000+ Global Events with over 600+ Conferences, 1200+ Symposiums and 1200+Workshops on diverse Medical, Pharmaceutical, Clinical, Engineering, Science, Technology, Business and Management field is organizing conferences all over the globe. It hosts numerous Cancer Conferences, Cancer meeting, global cancer conference, European Oncology Conferences, Surgical oncology like skin cancer conference, breast cancer conference, liver cancer conference, lung cancer meetings, and Oncology Conferences where knowledge transfer takes place through debates, round table discussions, poster presentations, workshops, symposia and exhibitions and which helps get possibilities for treating the diseases with new era, technology and research.



Why Brussels???

Brussels, a region of Belgium comprising 19 municipalities, is a city of contrasts with enormous diversity, experiencing cool climates all throughout the year. Brussels is also becoming known as a mecca of style, art, and design having bilingualism of Modern French and Old Dutch.

A cell undergoes many genetic and epigenetic changes as it transitions to malignancy. Malignant transformation is also accompanied by a progressive loss of tissue homeostasis and perturbations in tissue architecture that ultimately culminates in tumor cell invasion into the parenchyma and metastasis to distant organ sites. Increasingly, cancer biologists have begun to recognize that a critical component of this transformation journey involves marked alterations in the mechanical phenotype of the cell and its surrounding microenvironment. These mechanical differences include modifications in cell and tissue structure, adaptive force-induced changes in the environment, altered processing of micromechanical cues encoded in the extracellular matrix (ECM), and cell-directed remodeling of the extracellular stroma. Here, we review critical steps in this "force journey," including mechanical contributions to tissue dysplasia, invasion of the ECM, and metastasis. We discuss the biophysical basis of this force journey and present recent advances in the measurement of cellular mechanical properties in vitro and in vivo. We end by describing examples of molecular mechanisms through which tumor cells sense, process and respond to mechanical forces in their environment. While our understanding of the mechanical components of tumor growth, survival and motility remains in its infancy, considerable work has already yielded valuable insight into the molecular basis of force-dependent tumor pathophysiology, which offers new directions in cancer chemotherapeutics.

Summary Interleukin-18 (IL-18, interferon [IFN]-gamma-inducing factor) is a proinflammatory cytokine converted to a biologically active molecule by interleukin (IL)-1beta converting enzyme (caspase-1). A wide range of normal and cancer cell types can produce and respond to IL-18 through a specific receptor (IL-18R) belonging to the toll-like receptor family. The activity of IL-18 is regulated by IL-18-binding protein (IL-18bp), a secreted protein possessing the ability to neutralize IL-18 and whose blood level is affected by renal function and is induced by IFNgamma. IL-18 plays a central role in inflammation and immune response, contributing to the pathogenesis and pathophysiology of infectious and inflammatory diseases. Because immune-stimulating effects of IL-18 have antineoplastic properties, IL-18 has been proposed as a novel adjuvant therapy against cancer. However, IL-18 increases in the blood of the majority of cancer patients and has been associated with disease progression and, in some cancer types, with metastatic recurrence risk and poor clinical outcome and survival. Under experimental conditions, cancer cells can also escape immune recognition, increase their adherence to the microvascular wall and even induce production of angiogenic and tumor growth-stimulating factors via IL-18-dependent mechanism. This is particularly visible in melanoma cells. Thus, the role of IL-18 in cancer progression and metastasis remains controversial. This review examines the clinical correlations and biological effects of IL-18 during cancer development and highlights recent experimental insights into prometastatic and proangiogenic effects of IL-18 and the use of IL-18bp against cancer progression.

The goal of this project is to develop and utilize a microfluidic device to isolate and enrich tumor cells circulating in peripheral blood. Circulating tumor cells (CTCs) have been used as biomarkers for cancer diagnostics and prognosis. However, the rarity of these cells (roughly 1 in a billion) poses a technological challenge to sort and concentrate them. CTCs hold potential sources for early detection, characterization, monitoring of cancers, and development of personalized treatment. The project is currently funded by the US National Cancer Institute (NCI) of the National Institutes of Health (NIH).

In this paper we introduce a new mixed-integer linear programming (MIP) model that explicitly integrates the spread of cancer cells into a spatio-temporal reaction-diffusion (RD) model of cancer growth, while taking into account treatment effects. This linear but non-convex model appears to be the first of its kind by determining the optimal sequence of the typically prescribed cancer treatment methods-surgery (S), chemotherapy (C), and radiotherapy (R)-while minimizing the newly generated tumor cells for early-stage breast cancer in a unique three-dimensional (3D) spatio-temporal system. The quadratically-constrained cancer growth dynamics and treatment impact formulations are linearized by using linearization as well as approximation techniques. Under the supervision of medical oncologists and utilizing several literature resources for the parameter values, the effectiveness of treatment combinations for breast cancer specified with different sequences (i.e., SRC, SCR, CR, RC) are compared by tracking the number of cancer cells at the end of each treatment modality. Our results provide the optimal dosages for chemotherapy and radiation treatments, while minimizing the growth of new cancer cells.

The majority of men with progressive prostate cancer develop metastases with the skeleton being the most prevalent metastatic site. Unlike many other tumors that metastasize to bone and form osteolytic lesions, prostate carcinomas form osteoblastic lesions. However, histological evaluation of these lesions reveals the presence of underlying osteoclastic activity. These lesions are painful, resulting in diminished quality of life of the patient. There is emerging evidence that prostate carcinomas establish and thrive in the skeleton due to cross-talk between the bone microenvironment and tumor cells. Bone provides chemotactic factors, adhesion factors, and growth factors that allow the prostate carcinoma cells to target and proliferate in the skeleton. The prostate carcinoma cells reciprocate through production of osteoblastic and osteolytic factors that modulate bone remodeling. The prostate carcinoma-induced osteolysis promotes release of the many growth factors within the bone extracellular matrix thus further enhancing the progression of the metastases. This review focuses on the interaction between the bone and the prostate carcinoma cells that allow for development and progression of prostate carcinoma skeletal metastases.

Osteosarcoma (OS) is a class of cancer originating from bone, mainly afflicting children or young adults. It is the second highest cause of cancer-related death in these age groups, mainly due to development of often fatal metastasis, usually in the lungs. Survival for these patients is poor despite the aggressive use of surgery, chemotherapy, and/or radiotherapy. Thus, new effective drugs and other forms of therapy are needed. This article reviews the biology and the state of the art management of OS. New experimental drugs and potential therapies targeting molecular pathways of OS are also discussed.

Cancer is a major health problem around the world. Research efforts in the last few decades have been successful in providing better and effective treatments against both early stage and localized cancer, but clinical options against advanced metastatic stage/s of cancer remain limited. The high morbidity and mortality in most of the cancers are attributed to their metastatic spread to distant organs. Due to its extreme clinical relevance, metastasis has been extensively studied and is now understood as a highly complex biological event that involves multiple steps including acquisition of invasiveness by cancer cells, intravasation into circulatory system, survival in the circulation, arrest in microvasculature, extravasation, and growth at distant organs. The increasing understanding of molecular underpinnings of these events has provided excellent opportunity to target metastasis especially through nontoxic and biologically effective nutraceuticals. Silibinin, a popular dietary supplement isolated from milk thistle seed extracts, is one such natural agent that has shown biological efficacy through pleiotropic mechanisms against a variety of cancers and is currently in clinical trials. Recent preclinical studies have also shown strong efficacy of silibinin to target cancer cell’s migratory and invasive characteristics as well as their ability to metastasize to distant organs. Detailed mechanistic analyses revealed that silibinin targets signaling molecules involved in the regulation of epithelial-to-mesenchymal transition, proteases activation, adhesion, motility, invasiveness as well as the supportive tumor-microenvironment components, thereby inhibiting metastasis. Overall, the long history of human use, remarkable nontoxicity, and preclinical efficacy strongly favor the clinical use of silibinin against advanced metastatic cancers.

Cutaneous malignant melanoma (CMM) rates have been increasing in the United States at an average rate of about 4% per year. In 1987, it was estimated that there would be 25,800 cases and 5,800 deaths from CMM in the United States. The exact cause of the increase is unknown, but there is evidence to suggest that increasing exposure to the ultraviolet B (UVB) radiation present in sunlight may be partly responsible. The evidence includes: 1. the fact that higher CMM incidence rates are observed in people with lesser amounts of skin pigment (which blocks penetration of UV); 2. a correlation of higher CMM rates with decreasing latitude and increasing UVB levels; 3. the observation that freckles and nevi (precursors to CMM) are induced by solar exposure; 4. differences in CMM rates between natives and immigrants to sunny climates; 5. high rates of CMM in patients who cannot repair UVB-induced DNA damage; and 6. the indication that sun exposure at early ages and of an intermittent nature results in higher CMM risks. With the concern that depletion of stratospheric ozone could result in increasing levels of UVB, it has become important to understand the relationship between UVB and CMM in order to estimate the increases in CMM that would be expected with ozone depletion. When empirical relationships between UVB and CMM incidence and mortality rates were derived and used to estimate the impact of stratospheric ozone depletion, a 1% depletion of ozone was predicted to result in increases of 1%-2% in CMM incidence and 0.8%-1.5% in CMM mortality.

Two main kinds of immune strategy are possible against neoplasia. The first potentiates a selected effector arm. In vitro culture with exogenous interleukin-2 (IL-2) increases the activity of natural killer cells and leads to the expansion ofT cytotoxic lymphocytes. Systemic reinfusion of both of these cells with high doses of IL-2 mediates the regression of a variety of murine and human tumors. In an alternative strategy, a few regulatory lymphocytes turn on immune reactivity by triggering a cascade of interconnected effector functions. The efficacy of this strategy rests on the repertoire of effector mechanisms moved to action. An effective immunoregulatory maneuver is the addition of helper determinants on the surface of tumor cells. Its power can be further increased by the pre-induction of helper T lymphocytes specific to the helper determinants. This approach can be achieved in mice by coupling muramyl dipeptides to tumor cells, along with eliciting T lymphocytes specifically reactive to Bacillus Calmette-Guerin. Noncytotoxic T helper lymphocytes produce factors which recruit nonspecific (macrophages) as well as specific (cytolytic T lymphocytes) anti-tumor attacking cells. In this way protection can be afforded against primary tumors and metastases, as well as leukemia cells. As the activity of helper lymphocytes rests mostly on lymphokine release, the use of molecularly defined lymphokines mimicking T-helper functions has also been attempted. In a few experimental models, the association of low doses of IL-2 with non-reactive lymphocytes from tumor-bearing mice promotes an effective anti-tumor reaction in the host. Moreover, the combination of distinct lymphokines can also build a molecularly defined helper system able to activate in sequence non-specific and specific anti-tumor reactions in vivo. Trials intended to evaluate the clinical impact of these helper approaches in the management of human tumors are being started or are already under way.