Cancer Metastasis & Angiogenesis

Prostate cancer characteristically induces osteoblastic bone metastasis, for which no therapies are available. A dual kinase inhibitor of c-Met and VEGFR-2 (cabozantinib) was shown to reduce prostate cancer growth in bone, with evidence for suppressing osteoblastic activity. However, c-Met and VEGFR2 signaling in osteoblasts in the context of bone metastasis remain unclear. Here we show using cultured osteoblasts that hepatocyte growth factor (HGF) and VEGF-A increased receptor activator of NFkB ligand (RANKL) and M-CSF, two essential factors for osteoclastogenesis. Insulin-like growth factor-1 (IGF1) also increased RANKL and M-CSF via c-Met transactivation. The conditioned media from IGF1-, HGF-, or VEGFA-treated osteoblasts promoted osteoclastogenesis that was reversed by inhibiting c-Met and/or VEGFR2 in osteoblasts. In vivo experiments used cabozantinib-resistant prostate cancer cells (PC-3 and C4-2B) to test the effects of c-Met/VEGFR2 inhibition specifically in osteoblasts. Cabozantinib (60 mg/kg, 3 weeks) suppressed tumor growth in bone and reduced expression of RANKL and M-CSF and subsequent tumor-induced osteolysis. Collectively, inhibition of c-Met and VEGFR2 in osteoblasts reduced RANKL and M-CSF expression, and associated with reduction of tumor-induced osteolysis, suggesting that c-Met and VEGFR2 are promising therapeutic targets in bone metastasis.

This article describes relationships between follicle-stimulating
hormone (FSH), vascular endothelial growth factor (VEGF), and other modulators of prostatic cancer, in order to help optimize treatment decisions. A comprehensive literature search of PubMed and relevant congress abstract databases was conducted using combinations of the key words prostate cancer, follicle-stimulating hormone, vascular endothelial growth factor, inhibins/activins, gonadotropin-releasing hormone (GnRH)/luteinizing hormone-releasing hormone (LHRH) receptor agonists/antagonists, and angiogenesis/neogenesis. This was followed by a consensus meeting of prostate cancer experts to discuss current knowledge surrounding FSH and the relevant evidence for its role in the development and progression of prostate cancer.
Our understanding of prostate cancer and its progression
indicate an increase in levels of FSH and the FSH receptor, along with alterations in key modulatory proteins that regulate FSH synthesis and receptor signaling. Elevations in VEGF and differential modulation of testosterone with GnRH/LHRH agonists and antagonists may contribute to treatment outcomes. Considerable evidence supports the hypothesis that dysregulation of the FSH system plays a role in both the development and progression of prostate cancer. Data indicate that FSH can be modulated by the choice of treatment intervention, especially when androgen-deprivation therapy
is used.

The lymphatic vasculature provides a major route for tumor metastasis and inhibiting neolymphangiogenesis induced by tumors can reduce metastasis in animal models. Developmental biology studies have identified the transcription factor SOX18 as a critical switch for lymphangiogenesis in the mouse embryo. Here, we show that SOX18 is also critical for tumor-induced lymphangiogenesis, and we show that suppressing SOX18 function is sufficient to impede tumor metastasis. Immunofluorescence analysis of murine tumor xenografts showed that SOX18 is reexpressed during tumor-induced neolymphangiogenesis. Tumors generated by implantation of firefly luciferase-expressing B16-F10 melanoma cells exhibited a reduced rate of metastasis to the regional draining lymph node in Sox18-deficient mice, as assessed by live bioluminescence imaging. Lower metastatic rates correlated with reduced tumoral lymphatic vessel density and diameter and with impaired drainage of peritumoral injected liposomes specific for lymph vessels from the sentinel lymph nodes. Overall, our findings suggested that SOX18 induction is a key step in mediating tumor lymphangiogenesis and metastasis, and they identify SOX18 as a potential therapeutic target for metastatic blockade.

Cancer is the second leading
cause of death in the world. The causes of cancer
are diverse, complex, and only partially understood.
Altered expression of the microRNA-34 family has
been determined to be involved in the pathogenesis
of many cancers. Expression analysis of the
microRNA-34 family has suggested that they play
significant roles in many aspects of cancer biology
including proliferation, invasion/metastasis,
migration, senescence/aging, angiogenesis,
epigenetic silencing and methylation by regulation
of the expression of their target genes

Izvleček Izhodišča: Žlezni rak želodca (adenokarcinom) zaradi neznačilnih bolezenskih znakov pogosto odkrijemo v poznih stadijih, zato je preživetje bolnikov zelo nizko. Danes vemo, da so tumorji želodca iz molekularnega vidika zelo heterogeni in da se razvijejo kot posledica večstopenjskega procesa različnih genomskih, genskih in epigenetskih sprememb. Pomembno vlogo pri razvoju rakavih celic imajo gensko ozadje bolnikov, kopičenje sprememb v genih in dejavniki iz okolja. Več desetletij trajajoče raziskave so razkrile veliko mutiranih genov, ki bi lahko bili odgovorni za razvoj tovrstnega raka. Kljub temu pa tako poti njegovega nastanka kot tudi zaporedje dogodkov, ki spremenijo normalne celice v rakave, še vedno niso pojasnjeni. V pričujočem prispevku so predstavljeni molekularni mehanizmi, ki so najverjetneje vpleteni v razvoj raka želodca.

Senescent fibroblasts are known to promote tumor growth. However, the exact mechanism remains largely unknown. An important clue comes from recent studies linking autophagy with the onset of senescence. Thus, autophagy and senescence may be part of the same physiological process, known as the autophagy-senescence transition (AST). To test this hypothesis, human fibroblasts immortalized with telomerase (hTERT-BJ1) were stably transfected with autophagy genes (BNIP3, CTSB or ATG16L1). Their overexpression was sufficient to induce a constitutive autophagic phenotype, with features of mitophagy, mitochondrial dysfunction and a shift toward aerobic glycolysis, resulting in L-lactate and ketone body production. Autophagic fibroblasts also showed features of senescence, with increased p21(WAF1/CIP1), a CDK inhibitor, cellular hypertrophy and increased β-galactosidase activity. Thus, we genetically validated the existence of the autophagy-senescence transition. Importantly, autophagic-senescent fibroblasts promoted tumor growth and metastasis, when co-injected with human breast cancer cells, independently of angiogenesis. Autophagic-senescent fibroblasts stimulated mitochondrial metabolism in adjacent cancer cells, when the two cell types were co-cultured, as visualized by MitoTracker staining. In particular, autophagic ATG16L1 fibroblasts, which produced large amounts of ketone bodies (3-hydroxy-butyrate), had the strongest effects and promoted metastasis by up to 11-fold. Conversely, expression of ATG16L1 in epithelial cancer cells inhibited tumor growth, indicating that the effects of autophagy are compartment-specific. Thus, autophagic-senescent fibroblasts metabolically promote tumor growth and metastasis, by paracrine production of high-energy mitochondrial fuels. Our current studies provide genetic support for the importance of "two-compartment tumor metabolism" in driving tumor growth and metastasis via a simple energy transfer mechanism. Finally, β-galactosidase, a known lysosomal enzyme and biomarker of senescence, was localized to the tumor stroma in human breast cancer tissues, providing in vivo support for our hypothesis. Bioinformatic analysis of genome-wide transcriptional profiles from tumor stroma, isolated from human breast cancers, also validated the onset of an autophagy-senescence transition. Taken together, these studies establish a new functional link between host aging, autophagy, the tumor microenvironment and cancer metabolism.

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.
Kindly find the attached file for conference details

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We sincerely hope that you will honour us by accepting our invitation

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Celina Crystal
Manager of oncology and conferences
P 702 508 5200 Ext 8033
#[email protected]

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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.

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).

To explain a bimodal pattern of hazard of relapse among early stage breast cancer patients identified in multiple databases, we proposed that late relapses result from steady stochastic progressions from single dormant malignant cells to avascular micrometastases and then on to growing deposits. However in order to explain early relapses, we had to postulate that something happens at about the time of surgery to provoke sudden exits from dormant phases to active growth and then to detection. Most relapses in breast cancer are in the early category. Recent data from Forget et al. suggest an unexpected mechanism. They retrospectively studied results from 327 consecutive breast cancer patients comparing various perioperative analgesics and anesthetics in one Belgian hospital and one surgeon. Patients were treated with mastectomy and conventional adjuvant therapy. Relapse hazard updated Sept 2011 are presented. A common Non-Steroidal Anti-Inflammatory Drug (NSAID) analgesic used in surgery produced far superior disease-free survival in the first 5 years after surgery. The expected prominent early relapse events in months 9-18 are reduced 5-fold. If this observation holds up to further scrutiny, it could mean that the simple use of this safe, inexpensive and effective anti-inflammatory agent at surgery might eliminate early relapses. Transient systemic inflammation accompanying surgery could facilitate angiogenesis of dormant micrometastases, proliferation of dormant single cells, and seeding of circulating cancer stem cells (perhaps in part released from bone marrow) resulting in early relapse and could have been effectively blocked by the perioperative anti-inflammatory agent.

Asthma affects more than 300 million people worldwide and its prevalence is still rising. Acute asthma attacks are characterized by severe symptoms such as breathlessness, wheezing, tightness of the chest, and coughing, which may lead to hospitalization or death. Besides the acute symptoms, asthma is characterized by persistent airway inflammation and airway wall remodeling. The term airway wall remodeling summarizes the structural changes in the airway wall: epithelial cell shedding, goblet cell hyperplasia, hyperplasia and hypertrophy of the airway smooth muscle (ASM) bundles, basement membrane thickening and increased vascular density. Airway wall remodeling starts early in the pathogenesis of asthma and today it is suggested that remodeling is a prerequisite for other asthma pathologies. The beneficial effect of bronchial thermoplasty in reducing asthma symptoms, together with the increased potential of ASM cells of asthmatics to produce inflammatory and angiogenic factors, indicate that the ASM cell is a major effector cell in the pathology of asthma. In the present review we discuss the ASM cell and its role in airway wall remodeling and angiogenesis.

In recent years, the use of diffusion weighted MRI (DW-MRI) has increased for the diagnosis of focal liver lesions (FLLs). DW-MRI may help in the differentiation of benign and malignant FLLs by measuring the apparent diffusion coefficient (ADC) values. Unfortunately, liver metastases present different histopathologic features with variable MRI signals within each lesion; this histologic variability explains the intra- and inter-lesion variations of ADC measurements. We present the case of a 64-year-old female with diagnosis of liver metastasis from small cell lung carcinoma admitted to the emergency unit due to symptoms of inappropriate antidiuretic hormone secretion. Quantitative comparison of two liver MRI, on admission and 2-months after transcatheter arterial chemoembolization showed persistence of the hyperintense metastatic lesions with significant difference in the ADC values in the with-in metastatic lesions (p = 0.001) and between normal tissue and liver metastases only at ...

Basal cell carcinoma (BCC) is the most commonly diagnosed cancer in humans, usually affecting elderly Caucasian men and skin regions mostly exposed to the sun, that rarely metastasizes. We report an unusual and aggressive case of multiple, non-syndromic metastatic BCC with an uncommon primary site in the chest and pulmonary metastases, treated successfully with surgery and vismodegib. A 51-year-old woman presented with a large pigmentary lesion of the chest, close to the sternum. She had the lesion for > 25 years and lately noticed multiple facial lesions. The diagnosis of multiple BCC was suspected and a punch biopsy of the primary lesion was performed. Diagnosis was confirmed by immunohistochemistry (BerEp4+, EMA− phenotype). After excision, staging with a thorax computed tomography scan revealed metastatic micro-nodules in the left lung, confirmed histologically after video-assisted thoracic surgical biopsy. Adjuvant chemotherapy with vismodegib was proposed and administered. ...

Abstract: Background and Objective: Angiogenesis is a mechanism by which new blood vessels are developed in healing and tumour tissues, where it is necessary for regeneration growth, tumour cells survival and metastasis. This study aimed to assess the angiogenesis mechanism among Sudanese females with breast cancer using anti-CD34 and anti-CD105 markers. Materials and Methods: Three hundred female representative Formalin-Fixed Paraffin-Embedded (FFPE) breast tissue blocks were included in this study. Of the 300 representative tissue blocks, 200 were breast cancer patient’s tissues (confirmed cases) and 100 were normal breast tissues (controls). Their ages mean±SD, 47.3±12.9 years. Results: The results showed the MVD of CD34 significantly increased in malignant lesions as compared to normal breast tissues. The mean of MVD CD34 and MVD CD105 showed statistical differences among different histologic types of breast cancer. Also, a strong positive correlation was detected between the manual and automated MVD counting methods. Also, the current study revealed no significant differences were observed in mean MVD counting for both markers and menopausal status or the age groups of the study population. Conclusion: The MVD is a good tool for assessing prognostic markers. The CD105 marker has a high specificity to the new evolving tumour vessels and is a useful predictor for angiogenesis and breast cancer metastasis.

Basal cell carcinoma (BCC) is the most commonly diagnosed cancer in humans, usually affecting elderly Caucasian men and skin regions mostly exposed to the sun, that rarely metastasizes. We report an unusual and aggressive case of multiple, non-syndromic metastatic BCC with an uncommon primary site in the chest and pulmonary metastases, treated successfully with surgery and vismodegib. A 51-year-old woman presented with a large pigmentary lesion of the chest, close to the sternum. She had the lesion for > 25 years and lately noticed multiple facial lesions. The diagnosis of multiple BCC was suspected and a punch biopsy of the primary lesion was performed. Diagnosis was confirmed by immunohistochemistry (BerEp4+, EMA− phenotype). After excision, staging with a thorax computed tomography scan revealed metastatic micro-nodules in the left lung, confirmed histologically after video-assisted thoracic surgical biopsy. Adjuvant chemotherapy with vismodegib was proposed and administered. At 30 days follow-up, thorax computed tomography scan was unaltered and her facial lesions showed significant regression. Although prognosis remains poor, early diagnosis and prompt management complimented by novel biological agents, like vismodegib, targeting disease pathogenesis, seems to bring promising results.

We are describing a strategy to target tumor associated macrophages (TAMs), using microR146a and microR222 to transfer them back to a physiological state, that would enable them fight inflammation and to initiate an immune response against a tumor.

Senescent fibroblasts are known to promote tumor growth. However, the exact mechanism remains largely unknown. An important clue comes from recent studies linking autophagy with the onset of senescence. Thus, autophagy and senescence may be part of the same physiological process, known as the autophagy-senescence transition (AST). To test this hypothesis, human fibroblasts immortalized with telomerase (hTeRT-BJ1) were stably transfected with autophagy genes (BNIp3, CTSB or ATG16L1). Their overexpression was sufficient to induce a constitutive autophagic phenotype, with features of mitophagy, mitochondrial dysfunction and a shift toward aerobic glycolysis, resulting in L-lactate and ketone body production. Autophagic fibroblasts also showed features of senescence, with increased p21(WAF1/CIp1), a CDK inhibitor, cellular hypertrophy and increased β-galactosidase activity. Thus, we genetically validated the existence of the autophagy-senescence transition. Importantly, autophagic-senescent fibroblasts promoted tumor growth and metastasis, when co-injected with human breast cancer cells, independently of angiogenesis. Autophagic-senescent fibroblasts stimulated mitochondrial metabolism in adjacent cancer cells, when the two cell types were co-cultured, as visualized by MitoTracker staining. In particular, autophagic ATG16L1 fibroblasts, which produced large amounts of ketone bodies (3-hydroxy-butyrate), had the strongest effects and promoted metastasis by up to 11-fold. Conversely, expression of ATG16L1 in epithelial cancer cells inhibited tumor growth, indicating that the effects of autophagy are compartment-specific. Thus, autophagic-senescent fibroblasts metabolically promote tumor growth and metastasis, by paracrine production of high-energy mitochondrial fuels. Our current studies provide genetic support for the importance of "two-compartment tumor metabolism" in driving tumor growth and metastasis via a simple energy transfer mechanism. Finally, β-galactosidase, a known lysosomal enzyme and biomarker of senescence, was localized to the tumor stroma in human breast cancer tissues, providing in vivo support for our hypothesis. Bioinformatic analysis of genome-wide transcriptional profiles from tumor stroma, isolated from human breast cancers, also validated the onset of an autophagy-senescence transition. Taken together, these studies establish a new functional link between host aging, autophagy, the tumor microenvironment and cancer metabolism.

The roles of the chemokine CCL5 and its receptor CCR5 in breast cancer progression remain unclear. Here, we conducted microarray analysis on 2,254 human breast cancer specimens and found increased expression of CCL5 and its receptor CCR5, but not CCR3, in the basal and HER-2 genetic subtypes. The subpopulation of human breast cancer cell lines found to express CCR5 displayed a functional response to CCL5. In addition, oncogene transformation induced CCR5 expression, and the subpopulation of cells that expressed functional CCR5 also displayed increased invasiveness. The CCR5 antagonists maraviroc or vicriviroc, developed to block CCR5 HIV coreceptor function, reduced in vitro invasion of basal breast cancer cells without affecting cell proliferation or viability, and maraviroc decreased pulmonary metastasis in a preclinical mouse model of breast cancer. Taken together, our findings provide evidence for the key role of CCL5/CCR5 in the invasiveness of basal breast cancer cells and suggest that CCR5 antagonists may be used as an adjuvant therapy to reduce the risk of metastasis in patients with the basal breast cancer subtype. Cancer Res; 72(15); 3839-50. Ó2012 AACR.

Vascular endothelial growth factor receptor (VEGFR) is an important receptor tyrosine kinase (RTK) in the induction of angiogenesis. Abnormal activation of VEGFR leads to several disorders including cancer. Nowadays, inhibition of VEGFR kinase has been one of the most powerful clinical strategies in cancer treatment and great efforts to design and synthesize small molecular VEGFR inhibitors for cancer research have been made in recent years. This review highlights the major progress and development of them, including their structure and pharmacophore features, biological activities and structure-activity relationships (SAR). Special attentions are paid to the compounds available in market or in advanced clinical stages.

In recent years, the use of diffusion weighted MRI (DW-MRI) has increased for the diagnosis of focal liver
lesions (FLLs). DW-MRI may help in the differentiation of benign and malignant FLLs by measuring the apparent
diffusion coefficient (ADC) values. Unfortunately, liver metastases present different histopathologic
features with variable MRI signals within each lesion; this histologic variability explains the intra- and interlesion
variations of ADC measurements. We present the case of a 64-year-old female with diagnosis of liver
metastasis from small cell lung carcinoma admitted to the emergency unit due to symptoms of inappropriate
antidiuretic hormone secretion. Quantitative comparison of two liver MRI, on admission and 2-months
after transcatheter arterial chemoembolization showed persistence of the hyperintense metastatic lesions
with significant difference in the ADC values in the with-in metastatic lesions (p = 0.001) and between normal
tissue and liver metastases only at the end of treatment (p < 0.001). Several publications state that DWMRI
is capable to predict the response to chemotherapy in malignant tumors, the histologic variability of
liver metastasis and their response to different treatments is reflected in intra- and inter-lesion variations
of ADC measurements that might delay an accurate imaging diagnosis. We present evidence of this variability,
which might encourage prospective clinical trials that would define better cut-off values, would help
understand the ADC biological behaviour, and would reach consensus about the best acquisition parameters
for this promising quantitative biomarker.
Key words. Diffusion magnetic resonance imaging. Liver. Neoplasm metastasis. Small cell lung carcinoma. Therapeutic
chemoembolization.

In the pediatric cancer neuroblastoma, clinically aggressive disease is associated with increased levels of angiogenesis stimulators and high vascular index. We and others have hypothesized that blocking angiogenesis may be effective treatment for this pediatric malignancy. However, little is known about the efficacy of antiangiogenic agents in pediatric malignancies. Recently, promising results have been reported in an adult phase I study of ABT-510, a peptide derivative of the natural angiogenic inhibitor thrombospondin-1. Histone deacetylase inhibitors, such as valproic acid (VPA), have also been shown to have antiangiogenic activity in several cancer models. In this study, we evaluated the effects of ABT-510 and VPA on neuroblastoma tumor growth and angiogenesis. Although only VPA was capable of blocking the proliferation of neuroblastoma cells and inducing neuroblastoma cell apoptosis in vitro, treatment with VPA or ABT-510 alone significantly suppressed the growth of neuroblastoma xenografts established from two different MYCN-amplified cell lines. Combination therapy more effectively inhibited the growth of small neuroblastoma xenografts than single-agent treatment, and in animals with large xenografts, total cessation of tumor growth was achieved with this treatment approach. The microvascular density was significantly reduced in the xenografts treated with combination therapy compared with controls or tumors treated with single agents. In addition, the number of structurally abnormal vessels was reduced, suggesting that these agents may ‘‘normalize’’ the tumor vasculature. Our results indicate that ABT-510 combined with VPA may be an effective antiangiogenic treatment strategy for children with high-risk neuroblastoma.

Synthesis of new palladium(II) complexes, [Pd(L)Cl] (C1) and [Pd(L)PPh3](ClO4) (C2), with ONS donor thioether
ligand (HL) is reported. All the complexes were thoroughly characterized by using numerous spectroscopic techniques like FT-IR, NMR and UV–visible spectroscopy and so forth. Distorted square planar geometries of the complexes were confirmed unambiguously by means of single crystal X–ray diffraction analysis. Moreover, DFT and TDDFT calculations were performed to interpret the electronic structure, redox and spectral properties of the complexes. Cytotoxicity of the complexes was evaluated in vitro using MTT assay on human gastric cancer cell lines (AGS). The anti-cancer effects of HL and palladium(II) complexes (C1/C2) on AGS cell lines were determined
by comparing the half maximal inhibitory concentration (IC50) values. The results revealed that synthesized
palladium(II) complexes (C1/C2) showed higher anti-cancer activity (IC50 =13.4 μM for C1 and 16.0 μM for C2) compare to HL against AGS cell lines (67.1 μM).

The lymphatic vasculature provides a major route for tumor metastasis and inhibiting neolymphangiogenesis induced by tumors can reduce metastasis in animal models. Developmental biology studies have identified the transcription factor SOX18 as a critical switch for lymphangiogenesis in the mouse embryo. Here, we show that SOX18 is also critical for tumor-induced lymphangiogenesis, and we show that suppressing SOX18 function is sufficient to impede tumor metastasis. Immunofluorescence analysis of murine tumor xenografts showed that SOX18 is reexpressed during tumor-induced neolymphangiogenesis. Tumors generated by implantation of firefly luciferase-expressing B16-F10 melanoma cells exhibited a reduced rate of metastasis to the regional draining lymph node in Sox18-deficient mice, as assessed by live bioluminescence imaging. Lower metastatic rates correlated with reduced tumoral lymphatic vessel density and diameter and with impaired drainage of peritumoral injected liposomes specific for lymph vessels from the sentinel lymph nodes. Overall, our findings suggested that SOX18 induction is a key step in mediating tumor lymphangiogenesis and metastasis, and they identify SOX18 as a potential therapeutic target for metastatic blockade. Cancer Res; 72(12); 3105-14. Ó2012 AACR.

Despite many treatment options, cancer remains a growing problem and has become the second leading cause of death globally. Here, we present fluorescence molecular tomography (FMT) data regarding the reversion of third generation co-cultured U87+DBTRG and patient-derived GBM tumor model after treatment with novel IL17A inhibitor named FLVM and FLVZ (organic derivatives of caffeic acid). FMT was used to determine tumor angiogenesis volume (assessment of number of blood vessel; the expression of angiogenic factors CD34 and other angiogenic cancer bio-markers) in U87+DBTRG and patient-derived gliomas. Immunohistochemistry was used to determine microvessel density [CD34], and cell proliferation [Ki67]. Western blot was used to assess the interleukin 17 A [IL17A], vascular endothelial growth factor [VEGF] and hypoxia-inducible factor-1α [HIF-1α]. Antibody array was used to assess the cancer bio-markers in co-cultured U87+DBTRG gliomas. Animal survival was found to be significantly increased (P < 0.0001) after FLVM treatment compared with control-IL17A. After FMT detection, FLVM, administered orally, was found to decrease tumor growth (P < 0.0001). FLVM and FLVZ administration resulted in significant decreases in tumor hypoxia [HIF-1α (P < 0.05)], angiogenesis [CD34 (P < 0.05)], VEGF, IL17A and cell proliferation [Ki67 (P < 0.05)] and caused a significant increase of Bax, caspase and FasL (P < 0.05), compared with untreated animals. Additionally, Leptin, LPL (P < 0.01), FFA (P < 0.05) and adipogenesis were downregulated and no additive toxicity was found in mice except calorie-restriction like effect. Use of FLVM can be considered as a novel inhibitor of IL17A for the treatment of human gliomas.

In the pediatric cancer neuroblastoma, clinically aggressive disease is associated with increased levels of angiogenesis stimulators and high vascular index. We and others have hypothesized that blocking angiogenesis may be effective treatment for this pediatric malignancy. However, little is known about the efficacy of antiangiogenic agents in pediatric malignancies. Recently, promising results have been reported in an adult phase I study of ABT-510, a peptide derivative of the natural angiogenic inhibitor thrombospondin-1. Histone deacetylase inhibitors, such as valproic acid (VPA), have also been shown to have antiangiogenic activity in several cancer models. In this study, we evaluated the effects of ABT-510 and VPA on neuroblastoma tumor growth and angiogenesis. Although only VPA was capable of blocking the proliferation of neuroblastoma cells and inducing neuroblastoma cell apoptosis in vitro, treatment with VPA or ABT-510 alone significantly suppressed the growth of neuroblastoma xenografts established from two different MYCN-amplified cell lines. Combination therapy more effectively inhibited the growth of small neuroblastoma xenografts than single-agent treatment, and in animals with large xenografts, total cessation of tumor growth was achieved with this treatment approach. The microvascular density was significantly reduced in the xenografts treated with combination therapy compared with controls or tumors treated with single agents. In addition, the number of structurally abnormal vessels was reduced, suggesting that these agents may ''normalize'' the tumor vasculature. Our results indicate that ABT-510 combined with VPA may be an effective antiangiogenic treatment strategy for children with high-risk neuroblastoma. [Cancer Res 2007;67(4):1716-24]

In the clinical evolution of malign tumors, prognosis depends on whether metastasis develops or not. Biologically speaking, the formation of metastasis implies the existence of tumor cells capable of successfully performing all the steps in the metastatic process: local invasion, lymphatic or hematogenous dissemination, arrest in the microvascular bed of an organ, extravasation and growth of a secondary colony. Clinical observations have demonstrated that for each primary tumor there is a colonization pattern determined by the characteristics of the microvascular endothelium and the functional environment of the target organ. Moreover, the formation of metastasis depends on at least two additional factors: a) tumor cell-tumor cell and tumor cell-host cell relations modulated by intercellular contact and/or soluble paracrine or autocrine growth factors; b) the antitumor efficiency of the immune system, mediated primarily by the action of NK/LAK cells, macrophages and cytolytic T-lymphocytes, whose activity is in turn regulated by a complex of cytokines, including interferons, tumor necrosis factors and interleukins. In this work, we first review certain aspects of tumor biology that are specifically involved in tumor cell-host cell interactions determining non-random metastatic pattern distribution, and then review the implication of certain cytokines in the regulation of tumor proliferation.