Metastasis

Lymphoma is the most common lymphoproliferative disorder in cats. Cutaneous lymphoma, however, is a rare form of extranodal lymphoma. Recently, several cutaneous lymphomas at the tarsal region have been reported in cats. As it differs clinically and histopathologically from the common cutaneous lymphoma, it was denominated cutaneous tarsal lymphoma. The present study describes the case of a 13-year-old male domestic longhair cat that presented with a subcutaneous mass, of 30-days evolution, at the tarsal region of the right pelvic limb. Histopathology analysis showed malignant neoplasia of round cells, morphologically suggestive of large cell lymphoma. Immunohistochemistry confirmed the diagnosis of B-immunoblastic lymphoma. Patient was treated with lomustine, and prednisolone with an overall survival time of 2.1 months. The aggressiveness of this feline lymphoma reinforces the need for further studies to understand better the disease progression and to establish improved therapeutic protocols that can increase survival time and improve quality of life of these patients.

Breast and prostate cancers preferentially metastasise to bone tissue, with metastatic lesions
forming in the skeletons of most patients. On arriving in bone tissue, disseminated tumour cells
enter a mechanical microenvironment that is substantially different to that of the primary tumour
and is largely regulated by bone cells. Osteocytes, the most ubiquitous bone cell type, orchestrate
healthy bone remodelling in response to physical exercise. However, the effects of mechanical
loading of osteocytes on cancer cell behaviour is still poorly understood. The aim of this study
was to characterise the effects of osteocyte mechanical stimulation on the behaviour of breast and
prostate cancer cells. To replicate an osteocyte-controlled environment, this study treated breast
(MDA-MB-231 and MCF-7) and prostate (PC-3 and LNCaP) cancer cell lines with conditioned media
from MLO-Y4 osteocyte-like cells exposed to mechanical stimulation in the form of fluid shear stress.
We found that osteocyte paracrine signalling acted to inhibit metastatic breast and prostate tumour
growth, characterised by reduced proliferation and invasion and increased migration. In breast
cancer cells, these effects were largely reversed by mechanical stimulation of osteocytes. In contrast,
conditioned media from mechanically stimulated osteocytes had no effect on prostate cancer cells.
To further investigate these interactions, we developed a microfluidic organ-chip model using the
Emulate platform. This new organ-chip model enabled analysis of cancer cell migration, proliferation
and invasion in the presence of mechanical stimulation of osteocytes by fluid shear stress, resulting
in increased invasion of breast and prostate cancer cells. These findings demonstrate the importance
of osteocytes and mechanical loading in regulating cancer cell behaviour and the need to incorporate
these factors into predictive in vitro models of bone metastasis.

As a field we have made tremendous strides in treating breast cancer, with a decline in the past 30 years of overall breast cancer mortality. However, this progress is met with little affect once the disease spreads beyond the primary site. With a 5-year survival rate of 22%, 10-year of 13%, for those patients with metastatic breast cancer (mBC), our ability to effectively treat wide spread disease is minimal. A major contributing factor to this ineffectiveness is the complex make-up, or heterogeneity, of the primary site. Within a primary tumor, secreted factors, malignant and pre-malignant epithelial cells, immune cells, stromal fibroblasts and many others all reside alongside each other creating a dynamic environment contributing to metastasis. Furthermore, heterogeneity contributes to our lack of understanding regarding the cells' remarkable ability to undergo epithelial/non-cancer stem cell (CSC) to mesenchymal/CSC (E-M/CSC) plasticity. The enhanced invasion & motility, tumor-initiating potential, and acquired therapeutic resistance which accompanies E-M/CSC plasticity implicates a significant role in metastasis. While most work trying to understand E-M/CSC plasticity has been done on malignant cells, recent evidence is emerging concerning the ability for pre-malignant cells to undergo E-M/CSC plasticity and contribute to the metastatic process. Here we will discuss the importance of E-M/CSC plasticity within malignant and pre-malignant populations of the tumor. Moreover, we will discuss how one may potentially target these populations, ultimately disrupting the metastatic cascade and increasing patient survival for those with mBC.

Cancer stem cells (CSCs) refer to a subset of tumor cells with the potential to self-renew and differentiate into different cancer subtypes, including leukemias and solid tumors. Dysregulated gene expression and alteration of critical signaling pathways have been observed in CSCs, compared to low-tumorigenic bulk tumor cells. CSCs are thought to be responsible for tumor onset, self-renewal/maintenance, recurrence, distant metastasis, angiogenesis, and drug/radiation resistance. In recent years, CSCs have attracted a great deal of attention due to the remarkable potential for the development of specific therapies targeting CSCs and the identification of key molecules that play a critical role in controlling the unique features of CSC-enriched populations. During the last several years, a tremendous amount of work has been done on developing new drugs and therapeutic products, such as small molecule inhibitors, antibodies, and
small interfering RNAs (siRNAs). These CSC-targeting agents selectively inhibit key components of various intrinsic signaling
pathways or specific cell surface markers of CSCs. Many novel therapeutic agents and new molecular targeting compounds have been tested, some of which are currently under investigation in preclinical and clinical trials. In this review
article, we provide an overview of the current status of the CSC hypothesis and discuss the various critical signaling pathways and specific cell surface markers involved in the development and maintenance of CSC populations. In addition, we also review various patents and CSC-targeting therapeutic strategies that may eventually lead to eradication of both bulk tumor cells and CSCs.

Colorectal cancer (CRC) is one of the most common cancer types and represents a major therapeutic challenge. Although initial events in colorectal carcinogenesis are relatively well characterized and treatment for early-stage disease has significantly improved over the last decades, the mechanisms underlying metastasis – the main cause of death – remain poorly understood. Correspondingly, no effective therapy is currently available for advanced or metastatic disease. There is increasing evidence that colorectal cancer is hierarchically organized and sustained by cancer stem cells, in concert with various stromal cell types. Here, we review the interplay between cancer stem cells and their microenvironment in promoting metas-tasis and discuss recent insights relating to both patient prognosis and novel targeted treatment strategies. A better understanding of these topics may aid the prevention or reduction of metastatic burden.

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.

Metastatic complications are responsible for more than 90% of cancer-related deaths. The progression from an isolated tumor to disseminated metastatic disease is a multistep process, with each step involving intricate cross talk between the cancer cells and their non-cellular surroundings, the extracellular matrix (ECM). Many ECM proteins are significantly deregulated during the progression of cancer, causing both biochemical and biomechanical changes that together promote the metastatic cascade. In this review, the influence of several ECM proteins on these multiple steps of cancer spread is summarized. In addition, we highlight the promising (pre-)clinical data showing benefits of targeting these ECM macromolecules to prevent cancer progression.

Upon activation, platelets secrete more than 300 active substances from their intracellular granules. Platelet dense granule components, such as ADP and polyphosphates, contribute to haemostasis and coagulation, but also play a role in cancer metastasis. α-Granules contain multiple cytokines, mitogens, pro- and anti-inflammatory factors and other bioactive molecules that are essential regulators in the complex microenvironment of the growing thrombus but also contribute to a number of disease processes. Our understanding of the molecular mechanisms of secretion and the genetic regulation of granule biogenesis still remains incomplete. In this review we summarise our current understanding of the roles of platelet secretion in health and disease, and discuss some of the hypotheses that may explain how platelets may control the release of its many secreted components in a context-specific manner, to allow platelets to play multiple roles in health and disease.

There is now compelling evidence that the tumour stroma plays an important role in the pathogenesis of cancers of epithelial origin. The pre-eminent cell type of the stroma is carcinoma-associated fibroblasts. These cells demonstrate remarkable heterogeneity with activation and senescence being common stress responses. In this review, we summarise the part that these cells play in cancer, particularly oral cancer, and present evidence to show that activation and senescence reflect a unified programme of fibroblast differentiation. We report advances concerning the senescent fibroblast metabolome, mechanisms of gene regulation in these cells and ways in which epithelial cell adhesion is dysregulated by the fibroblast secretome. We suggest that the identification of fibroblast stress responses may be a valuable diagnostic tool in the determination of tumour behaviour and patient outcome. Further, the fact that stromal fibroblasts are a genetically stable diploid cell population suggests that they may be ideal therapeutic targets and early work in this context is encouraging.

The receptor for advanced glycation end products (RAGE) is highly expressed in various cancers and is correlated with poorer outcome in breast and other cancers. Here we tested the role of targeting RAGE by multiple approaches in the tumor and tumor microenvironment, to inhibit the metastatic process. We first tested how RAGE impacts tumor cell-intrinsic mechanisms using either RAGE overexpression or knockdown with short hairpin RNAs (shRNAs). RAGE ectopic overexpression in breast cancer cells increased MEK-EMT (MEK-epithelial-to-mesenchymal transition) signaling, transwell invasion and soft agar colony formation, and in vivo promoted lung metastasis independent of tumor growth. RAGE knockdown with multiple independent shRNAs in breast cancer cells led to decreased transwell invasion and soft agar colony formation, without affecting proliferation. In vivo, targeting RAGE shRNA knockdown in human and mouse breast cancer cells, decreased orthotopic tumor growth, reduced tumor angiogenesis and recruitment of inflammatory cells, and markedly decreased metastasis to the lung and liver in multiple xenograft and syngeneic mouse models. To test the non-tumor cell microenvironment role of RAGE, we performed syngeneic studies with orthotopically injected breast cancer cells in wild-type and RAGE-knockout C57BL6 mice. RAGE-knockout mice displayed striking impairment of tumor cell growth compared with wild-type mice, along with decreased mitogen-activated protein kinase signaling, tumor angiogenesis and inflammatory cell recruitment. To test the combined inhibition of RAGE in both tumor cell-intrinsic and non-tumor cells of the microenvironment, we performed in vivo treatment of xenografted tumors with FPS-ZM1 (1 mg/kg, two times per week). Compared with vehicle, FPS-ZM1 inhibited primary tumor growth, inhibited tumor angiogenesis and inflammatory cell recruitment and, most importantly, prevented metastasis to the lung and liver. These data demonstrate that RAGE drives tumor progression and metastasis through distinct tumor cell-intrinsic and-extrinsic mechanisms, and may represent a novel and therapeutically viable approach for treating metastatic cancers.

Malignant melanoma is an extremely aggressive and metastatic cancer, highly resistant to conventional treatment modalities. Understanding of fundamental mechanisms responsible for its genesis and progression is critical for development of successful chemotherapeutic treatment. It is becoming clear that melanoma results from complex changes in multiple signaling pathways that control cell proliferation and ability to evade the cell death processes. Impairment or hyper-activation of some components of these pathways may lead to malignant transformation and cancer development. In the present review we consider the current data on involvement of such signaling pathways as cyclin/CDK, Ras/Raf/MEK/MAPK, JNK/c-Jun/AP-1, PI3K/Akt/PTEN/mTOR, IKK/I-κB/NF-κB, Wnt/β-catenin, Notch, Jak/STAT, MITF and some growth factors in regulation of the cell cycle progression, apoptosis and development of human cutaneous melanoma. Understanding of molecular aberrations that underlie melanoma oncogenesis is essential for improvement of diagnosis, accurate prognosis assessment, and rational design of effective therapeutics. Inhibitors of these pathways may serve as promising tools for anti-melanoma targeted therapy. Some novel anti-melanoma target drugs are characterized.

The immunohistochemical expression of proliferating cell nuclear antigen (PCNA) and p53 was investigated in 9 cases of epithelial dysplasia and 38 cases of squamous cell carcinoma of the oral cavity. The intensity of immunoreactivity for each marker was assessed using a semiquantitative grading system, and was correlated with tumor differentiation, nuclear atypia and the patterns of invasive margins in the underlying connective tissue. PCNA expression, in dysplastic epithelium, was observed in the suprabasal and lower spinous layers; and the labeling grade and intensity of staining increased along the degree of cellular atypia. In 2 cases of dysplasia, weak positive immunoreactivity for p53 could be seen in a few isolated cells of the basal layer. In the squamous cell carcinoma, PCNA expression was correlated with the degree of tumor differentiation and nuclear atypia in well and moderately differentiated carcinoma, but not with the invasive pattern of tumor growth. Immunoreactivity for p53 was positive in 30 cases and showed a distribution pattern very similar to PCNA but with fewer positive cells. Three distinct categories of expression for PCNA and p53 were observed, among them a combination of intense reactivity for both markers was indicative of poor differentiation, higher nuclear atypia and more invasive growth of tumor cells.

The purpose of this review is to highlight several areas of lncRNA biology and cancer that we hope will provide some new insights for future research. These include the relationship of lncRNAs and the epithelial to mesenchymal transition (EMT) with a focus on transcriptional and alternative splicing mechanisms and mRNA stability through miRNAs. In addition, we highlight the potential role of enhancer e-lncRNAs, the importance of transposable elements in lncRNA biology, and finally the emerging area of using antisense oligonucleotides(ASOs) and small molecules to target lncRNAs and their therapeutic implications Manuscript Classifications: pointed out several areas need improvement. In case you can address their critiques, we will consider a revised version of it for publication with RNA biology. Reviewer 1: The authors provide a comprehensive review on LncRNA biology and the relationship of lncRNAs and the epithelial to mesenchymal transition (EMT) with a focus on transcriptional and alternative splicing mechanisms and mRNA stability through miRNAs. This review covers well most aspects of lncRNA studies and also talked about the future targeting lncRNAs with ASOs and small molecules. I will only point out some minor revisions that may help this manuscript and the authors can take to improve this review before it is accepted. 1.The modification of RNA is an emerging regulation for RNA biology and the m6A of lncRNA could be an interesting to talk in this review. I recommended the authors can add this to mRNA stability regulation part. We added a section at the very end on EMT and RNA modifications that we felt was more appropriate for this review rather than focusing on the area of mRNA stability. 2. In page8, line 7 of part "LncRNA regulation of miRNAs", the addition semicolon should be deleted.

Intermittent hypoxia within tumor microenvironments causes pro-oxidative stress impairing oxidative phos-phorylation (OxPhos) and increases mitochondrial production of reactive oxygen species (ROS). In primary tumors this provokes metabolic reprogramming of both tumor cells and cancer stem cells and emergence of highly metastatic cancer cells. Tumor reprogramming is initiated by activating nuclear respiratory factors and hypoxia-inducible factors in response to changes in oxygen and ROS levels. Hence, hypoxia-induced pro-oxidative stress drives invasion and metastasis. However, it is also the Achilles' heel of metastatic cancer cells because pro-oxi-dative agents further overload the mitochondria and intracellular milieu with excessive ROS to trigger apoptosis, whereas antioxidant agents promote their survival and tumor progression. Herein lies the metastatic tumor cell sensitivity to non-steroidal anti-inflammatory drugs (NSAIDs) and we and others have shown that the NSAID celecoxib exerts powerful pro-oxidative anticancer effects by directly targeting mitochondria to increase ROS production and trigger cancer cell death, including metastatic cancer cells and cancer stem cells. This review highlights the considerable benefits from appropriate NSAID use in humans against post-diagnosis metastatic tumors and the need to further develop their use as adjuvant therapy for advanced stage metastatic disease where they are already showing significantly improved clinical outcomes.

The proper management of neck in patients with head and neck malignancies is one of the unresolved oncologic questions. Cervical metastasis is one of the major risk factor and the best prognostic indicators for patient with head and neck cancer. Patients who present with tumors localized at the primary site without dissemination to regional lymph node enjoy an excellent prognosis and can be cured by appropriate use of surgery, radiotherapy or both. On the other hand once dissemination to regional lymph nodes takes place, the probability of 5 years survival, regardless of treatment, reduces to nearly one half of that seen in early staged patients. The purpose of this article is to study the current concepts in cervical lymph node metastases and development of various techniques in neck dissection to reduce morbidity while eradicating the pathology completely.

The ability of cancer to adapt renders it one of the most challenging pathologies of all time. It is the most dreaded pathological entity because of its capacity to metastasize to distant sites in the body, and 90% of all cancer-related deaths recorded to date are attributed to metastasis. Currently, three main theories have been proposed to explain the metastatic pathway of cancer: the epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET) hypothesis (1), the cancer stem cell hypothesis (2), and the macrophage-cancer cell fusion hybrid hypothesis (3). We propose a new hypothesis, i.e., under the effect of particular biochemical and/or physical stressors, cancer cells can undergo nuclear expulsion with subsequent macrophage engulfment and fusion, with the formation of cancer fusion cells (CFCs). The existence of CFCs, if confirmed, would represent a novel metastatic pathway and a shift in the extant dogma of cancer; consequently, new treatment targets would be available for this adaptive pathology.

Metastasis involves the migration of cancer cells from a primary tumor to invade and establish secondary tumors in distant organs, and it is the main cause for cancer-related deaths. Currently, the conventional cytostatic drugs target the proliferation of malignant cells, being ineffective in metastatic disease. This highlights the need to find new anti-metastatic drugs. Toxins isolated from snake venoms are a natural source of potentially useful molecular scaffolds to obtain agents with anti-migratory and anti-invasive effects in cancer cells. While there is greater evidence concerning the mechanisms of cell death induction of several snake toxin classes on cancer cells; only a reduced number of toxin classes have been reported on (i.e., disintegrins/disintegrin-like proteins, C-type lectin-like proteins, C-type lectins, serinproteases, cardiotoxins, snake venom cystatins) as inhibitors of adhesion, migration, and invasion of cancer cells. Here, we discuss the anti-metastatic mechanisms of snake toxins, distinguishing three targets, which involve (1) inhibition of extracellular matrix components-dependent adhesion and migration, (2) inhibition of epithelial-mesenchymal transition, and (3) inhibition of migration by alterations in the actin/cytoskeleton network.

In  the  last  decades  radiotherapy  induced  brain  injury  has  become  an  emerging issue  for physicians. Brain RT-induced injury has been classified, according to its time of onset, into acute, early delayed, and late forms.  The latter is not reversible. Etiopathogenesys of brain damage after RT has been at length discussed, vascular injury and white matter pathologic changes have been described.  In  our  study  we  described  the  neurological  cognitive  and  behavioural  disruption
produced by radiotherapy in primary brain neoplasia; moreover we demonstrated that the effect of radiation on the brain has a classic time dependent course, with a severity related to total radiation dose, individual fraction size, and the volume of brain irradiated. The patients, who suffered from the consequence of RT, did show slowness of executive functions, and profound alterations of frontal functions, such as attention focusing, mentation control, analogical judgement and insight, not differently from those obtained by the patients suffering from subcortical vascular dementia. The overall result of high dose- RT might be a severely demented, bedridden patient, who “has been  cured”  for  his  primary  disease,  the  brain  tumour,  but  it  constrains  us  to  make  serious consideration before radiation therapy onset and in order to implement new strategies to avoid this damage.

Imidazolium trans-tetrachloridodimethylsulfox
ideimidazolruthenate(III), NAMI-A, a novel antimetastatic
ruthenium complex was investigated towards affinity to
transferrin (Tf), whether Tf–Ru adducts might be formed
after its intravenous injection. Studies were focused on the
holotransferrin due to its preferential binding to transferrin
receptor. Here, we showed that holotransferrin is able
to bind NAMI-A as readily as apotransferrin. The simulation
of biological conditions of human serum performed by
application of simplified serum models allowed to analyse
ruthenium distribution between transferrin and albumin.
The presence of physiological concentration of albumin
(ca. 18-fold excess over Tf) resulted in a twofold decrease
of ruthenium binding to Tf. Interestingly, the introducing
of low-molecular-mass components of serum dramatically
increased the ruthenation of Tf. Intermolecular competition
binding studies between transferrin and albumin showed
that both proteins bound similar amount of ruthenium species.
Investigation of NAMI-A binding to Tf in human
serum showed that this protein was not the major binding
partner for Ru complex. However, in spite of many competing
proteins still the ruthenation of Tf was observed. The
lack of free Ru species (protein unbounded) after incubation
with human serum allowed to make an assumption of
high affinity of NAMI-A towards serum proteins.

The Macroscopic, histological and immunohistochemical aspects of lung acinar adenocarcinoma and the presence of nodules in the abdominal cavity of an adult female bovine are reported. In the necropsy analysis samples were collected from the: lung, heart, spleen, liver, pancreas, kidney, uterus, intestine, brain, and from nodules found in the lung and abdominal cavity, which were routinely processed to be stained by hematoxylin-eosin and for an immunohistochemistry exam with the antibodies: cytokeratin (dilution 1:200 μL) and vimentin (dilution 1:1000 μL). The histopathological examination revealed neoplastic epithelial cells with acini formation. The immunohistochemical examination of the tumor cells showed positive marking for cytokeratin and the absence of marking for vimentin. According to anatomical, morphological, and histopathological findings, as well as the result of the immunohistochemical examination, the tumor was characterized as lung acinar adenocarcinoma.

Introducción: Las metástasis cutáneas son diseminaciones de células malignas en la piel de tumores distantes que deben sospecharse en lesiones de rápido crecimiento sin respuesta al tratamiento. Representan un reto clínico pues no tienen una morfología macroscópica específica, mientras que histológicamente se localizan en dermis e hipodermis (carecen de com- ponente in situ). Presentación del caso: Se describe el caso de una mujer adulta mayor quien presenta metástasis en nariz de payaso tras desarrollar cáncer de pulmón con dos variantes distintas: adenocarcinoma y carcinoma escamocelular mal diferenciado macrocítico. Se confirmó la relación con estudio de inmunohistoquímica positivo para marcadores de carcinoma escamocelular pobremente diferenciado. Discusión: El signo de la nariz de payaso es una lesión inflamatoria nodular en la piel de la punta nasal como manifestación de metástasis cutánea de un tumor visceral. Se ha identificado junto con múltiples neoplasias entre las que se destacan el cáncer de pulmón en hombres y el cáncer mamario en mujeres. A pesar de su baja frecuencia se debe tener en cuenta por su efecto en la sobrevida de los pacientes. Conclusiones: La aparición de lesiones inflamatorias en punta nasal de rápido crecimiento que no respondan al tratamiento obliga realizar estudios de extensión para analizar la etiología.

Salivary gland tumours constitute about less than 4 % of all head and neck tumours. Pleomorphic adenoma, also called benign mixed tumour, is the most common tumour of the salivary glands. About 80–90 % of these tumours occur in the major salivary glands mainly parotid gland and 10 % of them occur in the minor salivary glands. The most common site for pleomorphic adenoma of the minor salivary glands is the palate, followed by the lips and the cheeks. Other rare sites include the floor of the mouth, tongue, tonsil, pharynx, retromolar area and the nasal cavity. Here, we are reporting a case of pleomorphic adenoma of the minor salivary glands of the soft palate in a 36-year-old Indian female. The mass was removed by wide local excision with adequate margins under general anesthesia. There was no recurrence seen after a follow-up period of 1 year.

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.

The vascular basement membrane (BM) is a thin and dense cross-linked extracellular matrix layer that covers and protects blood vessels. Understanding how cells cross the physical barrier of the vascular BM will provide greater insight into the potentially critical role of vascular BM breaching in cancer extravasation, leukocyte trafficking and angiogenic sprouting.
In the last year, new evidence has mechanistically linked the breaching of vascular BM with the formation of specific cellular micro-domains known as podosomes and invadopodia. These structures are specialized cell-matrix contacts with an inherent ability to degrade the extracellular matrix. Specifically, the formation of podosomes or invadopodia was shown as an important step in vascular sprouting and tumor cell extravasation, respectively. Here, we review and comment on these recent findings and explore the functions of podosomes and invadopodia within the context of pathological processes such as tumor dissemination and tumor angiogenesis.

Cancer of Unknown Primary (CUP) is a malignant widespread metastatic disease, which primary lesion cannot be identified by exact clinical Inspection. We reported a case of metastases from cancer of unknown primary here. A 58-year-old male presented with abdominal pain, backache, weakness and weight loss. Abdominopelvic sonography of the patient revealed two heterogeneous mass lesions in the right and left of the adrenal region. The primary site of the tumor was not identified According to our evaluation. We performed brain magnetic resonance imaging (CT) for the patient that showed a very large mainly peripheral enhancing mass lesion measuring 48×37 mm in the cerebellum as Glioblastoma multiforme (GBM). We did chemotherapy with platinum-based regimens including paclitaxel and carboplatin. In this case, the clinical situation of the patient swiftly deteriorated and unfortunately before doing local treatment for the brain mass we lost our case.

Marine algae Matrix metalloproteinases Phlorotannins Sulfated polysaccharides Metastasis Cancer Inflammation a b s t r a c t Matrix metalloproteinases are endopeptidases which belong to the group of metallo-proteinases that contribute for the extra-cellular matrix degradation, and several tissue remodeling processes. An imbalance in the regulation of these endopeptidases eventually leads to several severe pathological complications like cancers, cardiac, cartilage, and neu-rological related diseases. Hence inhibitory substances of metalloproteinases (MMPIs) could prove beneficial in the management of above specified pathological conditions. The available synthetic MMPIs that have been reported until now have few shortcomings and thus many of them could not make to the final clinical trials. Hence a growing interest among researchers on screening of MMPIs from different natural resources is evident and especially natural products from marine origin. As there has been an unparalleled contribution of several biologically active compounds from marine resources that have shown profound applications in nutraceuticals, cosmeceuticals, and pharmaceuticals, we have attempted to discuss the various MMPIs from edible seaweeds .

ABSTRACT
TITLE: Survival prognostic parameters in patients with spinal column epidural metastatic neoplasms
Study type: Doctors degree – 2013; Author: Jefferson Walter Daniel
DESCRIPTORS: Neoplasm metastasis; Spine; Prognosis; Survival; Surgical procedures, operative. INTRODUCTION: The primary outcome parameter of survival time in patients with neoplastic metastatic neoplasms located in the spine is the histological type and the site of the primary neoplasm. Secondary prognosis parameters estimate the survival period in the clinical situation of an unknown primary neoplasm. OBJECTIVES: 1. Identify survival prognosis parameters for patients harboring neoplastic epidural metastases situated in the spine. 2. Indicate survival prognosis parameters in the clinical situation of an unknown primary neoplasm. 3. Formulate a reasoning method to indicate surgical treatment. PATIENTS AND METHODS: Research project protocol: 281/10. Approved on August 27, 2010 by the Ethics Committee on Human Research of the Irmandade da Santa Casa de Misericórdia de São Paulo (Santa Casa de São Paulo - Faculty of Medical Sciences). Research was conducted at the Central Hospital of the Irmandade da Santa Casa de Misericórdia de São Paulo (Santa Casa de São Paulo - Faculty of Medical Sciences. The survey began in February 1997 and was cut in January 2011. The studies design was epidemiological, cohort, observational, longitudinal and prospective. The main inclusion criterion for the 52 research subjects was the period of survival, established as being between the dates of the surgical procedure to the date of death. Analytical analyses of associated variables compared the survival period after surgery to four patient sample groups. Survival prognostic parameters were: inability to ambulate; need for special care; tumor contact with the theca sac inside the spinal canal. Analyses were analytical in the preoperative and descriptive in the postoperative periods. RESULTS: The levels of statistical significance of the prognostic parameters were: the histological type of the neoplasm, p-value=0.023; the inability to ambulate, p-value=0.107; special care dependency, p- value=0.322; tumor contact to the theca sac, p-value=0,643. The results were statistically equivalent, there were no differences among the samples, equality was confirmed and the null hypothesis was accepted as being true (p>0.05). CONCLUSIONS: 1. The four survival prognosis parameters in the statistical order of significance are: histological type and / or the primary site of the tumor; inability to ambulate; institutional special care dependency; neoplasm contact to the theca sac within the spinal canal. 2. Unknown histological type and / or primary site of the tumor, prior to surgery, indicates the use of the three survival prognostic parameters: the inability to ambulate; institutional special care dependency; neoplasm contact to the theca sac within the spinal canal. 3. The three research prognosis parameters formulated four quantified criteria for surgical indications and are statistically justified. Videlicet: the patients’ clinical state scaled by Karnofskys’ Index with 30 points or over; progressive neurological deficit or fixed deficit functionally scaled as ASIA A, B, C or D; neoplastic metastasis nervous tissue compression inside the spinal canal scaled by the anatomical vertebral axial sector classification; survival prognosis estimated by Tokuhashi’s Index of 3 points or over.