Metastasis Of Different Types Research Articles

MCT4 has a potential to be used as a prognostic biomarker - a systematic review and meta-analysis.

The role of several metabolic changes, such as hypoxia and acidosis, in the tumour environment has caught the attention of researchers in cancer progression and invasion. Lactate transport is one of the acidosis-enhancing processes that are mediated via monocarboxylate transporters (MCTs). We conducted a systematic review and meta-analysis to investigate the expression of two cancer-relevant MCTs (MCT1 and MCT4) and their potential prognostic significance in patients with metastasis of different types of cancer. Studies were included if they reported the number of metastatic tissue samples expressing either low or high levels of MCT1 and/or MCT4 or those revealing the hazard ratios (HRs) of the overall survival (OS) or disease-free survival (DFS) as prognostic indicators. During the period between 2010 and 2018, a total of 20 articles including 3831 patients (56.3% males) were identified. There was a significant association between MCT4 expression (high versus low) and lymph node metastasis [odds ratio (OR)=1.87, 95% confidence interval (CI)=1.10-3.17, P=0.02] and distant metastasis (OR=2.18, 95%CI=1.65-2.86, P<0.001) and the correlation remained significant for colorectal and hepatic cancer in subgroup analysis. For survival analysis, patients with shorter OS periods exhibited a higher MCT4 expression [hazard ratio (HR)=1.78, 95%CI=1.49-2.13, P<0.001], while DFS was shorter in patients with high MCT1 (HR=1.48, 95%CI=1.04-2.10, P=0.03) and MCT4 expression (HR=1.70, 95%CI=1.19-2.42, P=0.003) when compared to their counterparts with low expression levels. Future research studies should consider the pharmacologic inhibition of MCT4 to effectively inhibit cancer progression to metastasis.

Abstract 4189: Limited-versus-extensive staging system for small cell prostate cancer

Abstract Introduction: Small cell prostate cancer (SCPC) is one of the most common extrapulmonary small cell cancers as well as one of the most common histology type among non-adenocarcinoma prostate cancers. While small cell lung cancer follows a limited-versus-extensive staging system which is different from the stage I to IV system used for non-small cell lung cancer, the prostate adenocarcinoma staging system is used in SCPC despite its distinct clinical feature and aggressive disease course. Limited by the rarity of SCPC, the optimal staging strategy for SCPC remains unknown. The present study aimed to investigate the prognostic value of limited-vs-extensive staging system in SCPC patients. Method: The Surveillance, Epidemiology, and End Results database was used to analyze the incidence and outcome of small cell prostate cancer. Patients diagnosed between the year 2004 through 2015 were included. Limited stage is defined as those without metastasis regardless of degree of local invasion. Extensive stage is defined as any metastasis to locoregional lymph node, to distant lymph node, or to distant organs. Result: A total of 364 SCPC patients are included in the study cohort, accounting for 0.05% of all prostate cancer cases (n=665,054). Age adjusted incidence of SCPC was 0.959 per 1,000,000 per year over the whole study period. The median age at diagnosis of SCPC is 71 years. The median overall survival is 9 months. In the 322 patients with known metastasis status, 243 (75.5%) patients are in extensive stage, whereas 79 patients are in limited stage. Patients in extensive stage are more likely to have PSA level greater than 20 than those in limited stage (26.3% vs 6%), but a similar proportion of patients in both groups have PSA level less than 4 (44.3% vs 40.0%). Compared to patients with extensive stage, those with limited stage disease had a significantly better overall survival (17 months vs 9 months, p&amp;lt;0.001) as well as disease specific survival (28 months vs 11 months, p&amp;lt;0.001). Limited stage patients with different T stage had a similar overall survival (p=0.43). Similarly, all extensive stage patients had similar outcome despite different types of metastasis (p=0.40). Multivariable analysis of treatment showed that only chemotherapy is associated with improved survival in extensive stage disease with HR of 0.46. Conclusion: SCPC patients can be staged to limited stage and extensive stage based on the absence versus presence of metastasis. T stage in limited stage patient and type of metastasis in extensive stage patient is not associated with different outcome. Citation Format: Salman Syed, Faisal Ali, Spyridon Basourakos, Zimu Gong. Limited-versus-extensive staging system for small cell prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4189.

Quantification of A Spectrum of Adhesion Molecules in Metastatic Cancer Patient Samples Using a Multiplex Bead-Based Immunoassay Panel

Abstract Metastasis to distant organs is responsible for ~90% of cancer-related deaths. Adhesion molecules are cell surface proteins that mediate the interactions between disseminated tumor cells and the endothelium of blood vessels present in the tumor microenvironment, and thus play a major role in tumor metastasis. Serum and plasma samples from patients with metastatic disease (head, neck, breast, pancreatic, gastric, and lung cancer patients) or healthy controls were assayed with a bead-based multiplex immunoassay which measured the concentration levels of the following adhesion molecules: ICAM-1, ICAM-2, ICAM-3, VCAM-1, PECAM-1, ALCAM-1, EpCAM, NCAM, E-selectin, P-selectin, L-selectin, PSGL-1, and CD44. Although limited by sample size, differential concentrations of assay targets were detected between healthy and disease-state samples. We have demonstrated that this multiplex panel is a robust tool for measuring the concentration of a spectrum of adhesion molecules with great efficiency and convenience. This panel will help screen and identify the adhesion molecules that may be universally or specifically involved in metastasis of different types of cancer.

Breaking down the Contradictory Roles of Histone Deacetylase SIRT1 in Human Breast Cancer.

Breast cancer (BC) is the most common type of cancer in women worldwide; it is a multifactorial genetic disease. Acetylation and deacetylation are major post-translational protein modifications that regulate gene expression and the activity of a myriad of oncoproteins. Aberrant deacetylase activity can promote or suppress tumorigenesis and cancer metastasis in different types of human cancers, including breast cancer. Sirtuin-1 (SIRT1) is a class-III histone deacetylase (HDAC) that deacetylates both histone and non-histone targets. The often-described ‘regulator of regulators’ is deeply implicated in apoptosis, gene regulation, genome maintenance, DNA repair, aging, and cancer development. However, despite the accumulated studies over the past decade, the role of SIRT1 in human breast cancer remains a subject of debate and controversy. The ambiguity surrounding the implications of SIRT1 in breast tumorigenesis stems from the discrepancy between studies, which have shown both tumor-suppressive and promoting functions of SIRT1. Furthermore, studies have shown that SIRT1 deficiency promotes or suppresses tumors in breast cancer, making it an attractive therapeutic target in cancer treatment. This review provides a comprehensive examination of the various implications of SIRT1 in breast cancer development and metastasis. We will also discuss the mechanisms underlying the conflicting roles of SIRT1, as well as its selective modulators, in breast carcinogenesis.

CX3CL1/fractalkine enhances prostate cancer spinal metastasis by activating the Src/FAK pathway.

Chemokines serve important roles in the development of cancer. C-X3-C motif chemokine ligand 1 (CX3CL1) has been demonstrated to promote metastases in different types of tumors. The authors' previous studies demonstrated that the CX3CL1 (also termed fractalkine)/steroid receptor coactivator (Src)/focal adhesion kinase (FAK) signaling pathway is associated with spinal metastasis. In the present study, it was observed that CX3CL1/C-X3-C motif chemokine receptor 1 (CX3CR1) was overexpressed in prostate cancer tissues with spinal metastasis compared with primary tumors. Overexpression of CX3CR1 induced cell proliferation, migration and invasion, and inhibited cellular apoptosis. However, repression of CX3CR1 reduced cell proliferation, migration and invasion, and increased cellular apoptosis. In addition, the Src/FAK pathway was activated by CX3CL1, which depends on the Tyr992 residue of epidermal growth factor receptor (EGFR) for phosphorylation. The inhibitors of these kinases repressed the cell migration induced by CX3CL1 or CX3CR1 overexpression. Furthermore, overexpression of CX3CR1 induced the spinal metastasis of prostate cancer in an in vivo mouse model. Therefore, CX3CL1 and its regulation of the EGFR, Src and FAK pathways may be potential targets for the early prevention of spinal metastasis in prostate cancer.

Frequency and Site of Skeletal Metastatic Lesion Detected by Bone Scintigraphy in Newly Diagnosed Asymptomatic Cancer Patients

&lt;p&gt;&lt;strong&gt;Objectives:&lt;/strong&gt; Bone is one of the most common organ for metastasis. Bone scintigraphy is widely used for staging of cancer patients before initiation of chemotherapy and adjuvant therapy and it can detect both symptomatic and asymptomatic bone metastases. The purpose of this study was to determine the frequency and site of metastatic bone lesion detected by bone scintigraphy in newly diagnosed asymptomatic cancer patients who werwe referred to National Institute of Nuclear Medicine &amp;amp; Allied Sciences (NINMAS) for bone scintigraphy.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Patients and Methods:&lt;/strong&gt; This cross sectional observational type of study was carried out in NINMAS from July 2015 to June 2016. A total of 116 newly diagnosed asymptomatic cancer patients referred for the first time bone scintigraphy were included in this study.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results:&lt;/strong&gt; Of the total 116 patients (57 male and 59 female; mean age: 54.8 ± 14.0 years), 46 (39.7%) patients had carcinoma breast, 30 (25.9%) patients had carcinoma prostate, 12(10.3%) patients had carcinoma lung, 8(6.9%) patients had carcinoma urinary bladder, 4(3.4%) patients had renal cell carcinoma and 16(13.8%) patients had other cancer. Bone scan was found positive for metastatic disease in 44.8% patients. Most common sites of bone metastases in different types of cancer in newly diagnosed asymptomatic cancer patients were rib, then hip bone, vertebral column (lumbar vertebra, thoracic vertebra respectively), sternum and skull.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion:&lt;/strong&gt; In this study, it was revealed that newly diagnosed asymptomatic cancer patients are frequently associated with metastatic bone disease, those can be detected by bone scintigraphy.&lt;/p&gt;&lt;p&gt;Bangladesh J. Nuclear Med. 20(1): 14-18, January 2017&lt;/p&gt;

Quantification of FDG-PET/CT with delayed imaging in patients with newly diagnosed recurrent breast cancer

BackgroundSeveral studies have shown the advantage of delayed-time-point imaging with 18F-FDG-PET/CT to distinguish malignant from benign uptake. This may be relevant in cancer diseases with low metabolism, such as breast cancer. We aimed at examining the change in SUV from 1 h (1h) to 3 h (3h) time-point imaging in local and distant lesions in patients with recurrent breast cancer. Furthermore, we investigated the effect of partial volume correction in the different types of metastases, using semi-automatic quantitative software (ROVER™).MethodsOne-hundred and two patients with suspected breast cancer recurrence underwent whole-body PET/CT scans 1h and 3h after FDG injection. Semi-quantitative standardised uptake values (SUVmax, SUVmean) and partial volume corrected SUVmean (cSUVmean), were estimated in malignant lesions, and as reference in healthy liver tissue. The change in quantitative measures from 1h to 3h was calculated, and SUVmean was compared to cSUVmean. Metastases were verified by biopsy.ResultsOf the 102 included patients, 41 had verified recurrent disease with in median 15 lesions (range 1-70) amounting to a total of 337 malignant lesions included in the analysis. SUVmax of malignant lesions increased from 6.4 ± 3.4 [0.9-19.7] (mean ± SD, min and max) at 1h to 8.1 ± 4.4 [0.7-29.7] at 3h. SUVmax in breast, lung, lymph node and bone lesions increased significantly (p < 0.0001) between 1h and 3h by on average 25, 40, 33, and 27%, respectively. A similar pattern was observed with (uncorrected) SUVmean. Partial volume correction increased SUVmean significantly, by 63 and 71% at 1h and 3h imaging, respectively. The highest impact was in breast lesions at 3h, where cSUVmean increased by 87% compared to SUVmean.ConclusionSUVs increased from 1h to 3h in malignant lesions, SUVs of distant recurrence were in general about twice as high as those of local recurrence. Partial volume correction caused significant increases in these values. However, it is questionable, if these relatively modest quantitative advances of 3h imaging are sufficient to warrant delayed imaging in this patient group.Trial registrationClinicalTrails.gov NCT01552655. Registered 28 February 2012, partly retrospectively registered.

Molecular Mechanisms of Nitric Oxide in Cancer Progression, Signal Transduction, and Metabolism.

Cancer is a complex disease, which not only involves the tumor but its microenvironment comprising different immune cells as well. Nitric oxide (NO) plays specific roles within tumor cells and the microenvironment and determines the rate of cancer progression, therapy efficacy, and patient prognosis. Recent Advances: Key understanding of the processes leading to dysregulated NO flux within the tumor microenvironment over the past decade has provided better understanding of the dichotomous role of NO in cancer and its importance in shaping the immune landscape. It is becoming increasingly evident that nitric oxide synthase 2 (NOS2)-mediated NO/reactive nitrogen oxide species (RNS) are heavily involved in cancer progression and metastasis in different types of tumor. More recent studies have found that NO from NOS2+ macrophages is required for cancer immunotherapy to be effective. NO/RNS, unlike other molecules, are unique in their ability to target a plethora of oncogenic pathways during cancer progression. In this review, we subcategorize the different levels of NO produced by cells and shed light on the context-dependent temporal effects on cancer signaling and metabolic shift in the tumor microenvironment. Understanding the source of NO and its spaciotemporal profile within the tumor microenvironment could help improve efficacy of cancer immunotherapies by improving tumor infiltration of immune cells for better tumor clearance.

MiR‑367 enhances the proliferation and invasion of cutaneous malignant melanoma by regulating phosphatase and tensin homolog expression.

Melanoma presents a serious threat to human health but the underlying mechanisms have not been fully identified. Increasing evidence indicates that microRNAs exert a significant influence on the tumorigenesis and metastasis of different types of cancer. The present study aimed to identify the role of microRNA (miR)-367 in the initiation and progression of melanoma and investigate its potential target. A total of 50 melanoma samples and 25 benign nevi tissues were used in the present study. Reverse transcription-quantitative polymerase chain reaction and western blot analysis were performed to determine the expression of mRNA and protein, respectively. Cell proliferation and invasion were assessed by CCK-8, wound healing and Transwell assays. A proposed target mRNA of miR-367 was determined using a luciferase reporter assay and an in vivo xenograft model was used to evaluate the function of miR-367 in the progression of melanoma. It was revealed that miR-367 was overexpressed in melanoma tissues and cell lines. The miR-367 level in tumor tissues was positively correlated with tumor thickness, tumor stage, lymph node involvement, distant metastasis and the patient survival rate. A high miR-367 level was observed to enhance the growth, migration and invasion of melanoma cells. Conversely, low miR-367 levels suppressed the proliferation and invasion of melanoma cells. Furthermore, miR-367 was revealed to bind directly to phosphatase and tensin homolog (PTEN) mRNA and regulate the expression of the PTEN protein. miR-367 markedly increased the growth and invasion of melanoma cells, whereas the cotransfection of PTEN vectors limited the promoting function of miR-367 in the proliferation and invasion of A375 cells. The upregulation of miR-367 promoted tumor growth in vivo. In conclusion, the results revealed that miR-367 serves a positive role in the development of melanoma and may be an important target for the treatment of cutaneous melanoma.

Human epidermal growth factor receptor 2 borderline mortality in breast cancer patients: Evidence from surveillance, epidemiology, and end results program population-based study

BackgroundBreast cancers with Human Epidermal Growth Factor Receptor 2 (HER2) borderline outcomes are very puzzling for patient management. To whether HER2 borderlines are having different prognostic status in comparison to HER2 positive/negative. MethodsThis is a study among women diagnosed with invasive breast cancer from 1973 to 2014 who were identified in the Surveillance, Epidemiology, and End Results (SEER) of 9 registries database and having diagnosed with HER2 status (N=102167), i.e. HER2 positive (N=14678), HER2 negative (N=85354) and HER2 borderline (N=2135). ResultsThis Surveillance, Epidemiology, and End Results (SEER) study represents the largest report of prospective invasive breast cancer with HER2 status till five years from the date of registration. The five years survival rate among HER2 borderline was found completely separate with HER2 positive and HER2 negative patients. In several subtypes of analysis, it has been found that status of survival among HER borderline patients is significantly poor than HER2 positive and HER2 negative. The likelihood of death in HER2 borderline is found high (15.06%) in comparison to HER2 positive (14.24%) and HER2 negative (6.49%) at the end of five years. Different types of metastasis like Bone, Brain, Liver, and Lung are also observed with the higher rate in HER2 borderline in comparison to HER2 negative.

The association between LncRNA HOTAIR and cancer lymph node metastasis and distant metastasis: a meta-analysis.

HOTAIR has been reported to be associated with development and metastasis in different types of cancer. This meta- analysis collected all relevant articles and explored the correlation of HOTAIR with lymph node metastasis (LNM) and distant metastasis (DM). A literature collection was conducted by searching PubMed, Web of Science, Google Scholar and Cochrane Library (up to Sep 11, 2016). The odds ratio (OR) with 95% confidence interval (95% CI) was calculated to assess the association with strength. Nineteen studies were included in this study, with a total of 1874 patients. The study objects were all Asians. We found high HOTAIR expression in tumor tissues was significantly correlated with LNM and DM, and analysis showed a pooled OR of 3.18 (95% CI: 2.10-4.81, p<0.00001) and 3.93 (95% CI: 2.39-6.47, p<0.00001), respectively. HOTAIR may serve as a novel diagnostic biomarker for cancer metastasis.

Utility of point shear wave elastography in characterisation of focal liver lesions

ABSTRACTBackground: The present study aimed at evaluation of the usefulness of point shear wave elastography (pSWE) in characterization of FLL(s) by quantifying their stiffness.Methods: In total, 197 patients (mean age was 56.57 years) with FLL(s) on conventional ultrasound were included. Final diagnoses, confirmed by imaging and/or biopsy whenever possible, included hepatocellular carcinoma (HCC) (n = 143), metastasis (n = 36), hemangioma (n = 16), and focal nodular hyperplasia (n = 2). Stiffness evaluation was performed by pSWE. Stiffness ratio (lesion to background liver) was calculated. ROC analysis was performed to evaluate the diagnostic accuracy of the stiffness value and stiffness ratio and to extract the optimal cutoff values for characterisation of FLL(s).Results: HCC was significantly softer than its surrounding liver parenchyma [5.43 (3.03) vs. 17.05 (8.53) kPa, p <0.001]. However, the stiffness values for the other examined FLLs were comparable to their surrounding liver parenchyma. No significant difference was detected across different types of metastases or between metastases and surrounding liver (p>0.05). Stiffness ratio was superior to stiffness value in discrimination of HCC from metastasis (AUROC, 0.91 vs. 0.51 respectively).Conclusion: pSWE could provide a complementary information about FLLs especially in differentiation between HCCs from metastases.

BRAF Mutation Status Concordance Between Primary Cutaneous Melanomas and Corresponding Metastases: A Review of the Latest Evidence

The identification of B-Raf proto-oncongene (BRAF) mutation and the emergence of targeted therapy marked a turning point in the treatment of melanoma. The study of mutation status concordance between primary tumors and metastases in this cancer has major treatment implications as it facilitates the selection of candidates for targeted therapy. This review analyzes the evidence on the level of mutation status concordance between primary tumors and different types of metastases in cutaneous melanoma and provides an overview of the advantages and disadvantages of the various methods used to detect BRAF mutations.

Prognostic role of plasma fibrinogen in patients with uterine leiomyosarcoma \u2013 a multicenter study

Fibrinogen has an important pathophysiological role in tumor cell progression and development of metastases in different types of cancer. The present study aimed to evaluate the role of pre-treatment fibrinogen plasma concentrations as a biomarker for tumor biology and prognosis in patients with uterine leiomyosarcoma (ULMS). Clinical data of patients with ULMS were assessed in this multi-center study Pre-therapeutic fibrinogen plasma concentrations were evaluated. We investigated the association between fibrinogen plasma levels and clinico-pathological parameters and performed univariate and multivariable survival analyses. In total, 70 women with ULMS were included into the analysis. Mean (SD) pre-treatment fibrinogen plasma levels were 480.2 (172.3) mg/dL. Patients with advanced tumor stage, increased tumor size and higher histological grading had higher fibrinogen levels (p = 0.02, p = 0.013, and p = 0.029, respectively). In ULMS patients with increased fibrinogen levels 5-year overall survival (OS) rates were 25.0% compared to 52.9% in ULMS patients with normal fibrinogen, respectively. Univariate survival analyses revealed that elevated fibrinogen plasma levels (p = 0.030), advanced tumor stage (p < 0.001) and undifferentiated histology (p = 0.003) showed association with unfavorable OS. In multivariable analysis, histological grade (p = 0.03) and tumor stage (0.02) were independently associated with survival. Elevated fibrinogen plasma levels were associated with aggressive tumor biology and poor prognosis in women with ULMS. Fibrinogen might be useful as a novel biomarker in ULMS.

Long non-coding RNA AFAP1-AS1 is a novel biomarker in various cancers: a systematic review and meta-analysis based on the literature and GEO datasets.

BackgroundGrowing evidence indicates that AFAP1-AS1 plays an important role in various cancers, suggesting that it might be a potential cancer biomarker.Materials and MethodsA meta-analysis was performed using microarray data obtained via the Affymetrix Human Genome U133 Plus 2.0 platform (found in the GEO database) and data obtained through a systematic search of PubMed and Web of Science. The pooled odds ratio (OR) and hazard ratio (HR) with 95% CI (confidence interval) were used to judge the value of biomarkers.ResultsA total of 30 studies were included in this meta-analysis, comprising a total of 3573 patients. AFAP1-AS1 was significantly linked with overall survival (OS) (HR = 1.58; 95% CI: 1.12–2.23) and recurrence-free survival (RFS) (HR = 2.32, 95% CI: 1.68–3.19). We found that AFAP1-AS1 was a risk factor in the prognoses of lung cancer (pooled HR: 1.54; 95% CI: 1.01–2.34), digestive system cancer (pooled HR: 1.87; 95% CI: 1.45–2.41) and nasopharyngeal carcinoma (HR: 11.82; 95% CI: 5.09–27.46). AFAP1-AS1 was also a risk factor for RFS in breast cancer (pooled HR = 2.90; 95% CI: 1.69–4.98), as well as TNM stage in both esophageal cancer (pooled OR = 1.90; 95% CI: 1.01–3.57) and colorectal cancer (OR = 6.72; 95% CI: 1.92–23.58). AFAP1-AS1 was significantly associated with lymph node metastasis in clear cell carcinoma (OR = 5.04; 95% CI: 2.36–10.78) and distant metastasis in pancreatic cancer (OR = 11.64; 95% CI: 2.13–63.78).ConclusionsAFAP1-AS1 can serve as a novel molecular marker predicting tumor progression, patient prognosis and lymph node metastasis in different types of cancers.

The Implications and Future Perspectives of Nanomedicine for Cancer Stem Cell Targeted Therapies.

Cancer stem cells (CSCs) are believed to exhibit distinctive self-renewal, proliferation, and differentiation capabilities, and thus play a significant role in various aspects of cancer. CSCs have significant impacts on the progression of tumors, drug resistance, recurrence and metastasis in different types of malignancies. Due to their primary role, most researchers have focused on developing anti-CSC therapeutic strategies, and tremendous efforts have been put to explore methods for selective eradication of these therapeutically resistant CSCs. In recent years, many reports have shown the use of CSCs-specific approaches such as ATP-binding cassette (ABC) transporters, blockade of self-renewal and survival of CSCs, CSCs surface markers targeted drugs delivery and eradication of the tumor microenvironment. Also, various therapeutic agents such as small molecule drugs, nucleic acids, and antibodies are said to destroy CSCs selectively. Targeted drug delivery holds the key to the success of most of the anti-CSCs based drugs/therapies. The convention CSCs-specific therapeutic agents, suffer from various problems. For instance, limited water solubility, small circulation time and inconsistent stability of conventional therapeutic agents have significantly limited their efficacy. Recent advancement in the drug delivery technology has demonstrated that specially designed nanocarrier-based drug delivery approaches (nanomedicine) can be useful in delivering sufficient amount of drug molecules even in the most interiors of CSCs niches and thus can overcome the limitations associated with the conventional free drug delivery methods. The nanomedicine has also been promising in designing effective therapeutic regime against pump-mediated drug resistance (ATP-driven) and reduces detrimental effects on normal stem cells. Here we focus on the biological processes regulating CSCs' drug resistance and various strategies developed so far to deal with them. We also review the various nanomedicine approaches developed so far to overcome these CSCs related issues and their future perspectives.

68Ga]PSMA-HBED-CC Uptake in Osteolytic, Osteoblastic, and Bone Marrow Metastases of Prostate Cancer Patients.

The aim of this study was to evaluate potential differences in "Glu-NH-CO-NH-Lys" radio-labeled with [68Ga]gallium N,N-bis[2-hydroxy-5-(carboxyethyl)benzyl]ethylenediamine-N,N-diacetic acid ([68Ga]PSMA-HBED-CC) uptake in osteolytic, osteoblastic, mixed, and bone marrow metastases in prostate cancer (PC) patients. This retrospective study was approved by the local ethics committee. Patients who received [68Ga]PSMA-HBED-CC positron emission tomography/computed tomography ([68Ga]PSMA-PET/CT) with at least one positive bone metastasis were included in this study. Only patients who have not received systemic therapy for their PC were included. Bone metastases had to be confirmed by at least one other imaging modality or follow-up investigation. The maximum standardized uptake value (SUVmax) and mean Hounsfield units (HUmean) of each metastasis were measured. Based on CT, each metastasis was classified as osteolytic (OL), osteoblastic (OB), bone marrow (BM), or mixed (M). One hundred fifty-four bone metastases in 30 patients were evaluated. Eighty out of 154 (51.9%) metastases were classified as OB, 21/154 (13.6%) as OL, 23/154 (14.9%) as M, and 30/154 (19.5%) as BM. The SUVmax for the different types of metastases were 10.6±7.07 (OB), 24.0±19.3 (OL), 16.0±21.0 (M), and 14.7±9.9 (BM). The SUVmax of OB vs. OL and OB vs. BM metastases differed significantly (p≤0.025). A significant negative correlation between HUmean and SUVmax (r=-0.23, p<0.05) was measured. [68Ga]PSMA-HBED-CC uptake is higher in osteolytic and bone marrow metastases compared to osteoblastic metastases. Information derived from [68Ga]PSMA-PET and CT complement each other for the reliable diagnosis of the different types of bone metastases in PC patients.

Concordancia mutacional de BRAF entre melanoma primario cutáneo y sus correspondientes metástasis. Revisión de la evidencia actual

The identification of B-Raf proto-oncongene (BRAF) mutation and the emergence of targeted therapy marked a turning point in the treatment of melanoma. The study of mutation status concordance between primary tumors and metastases in this cancer has major treatment implications as it facilitates the selection of candidates for targeted therapy. This review analyzes the evidence on the level of mutation status concordance between primary tumors and different types of metastases in cutaneous melanoma and provides an overview of the advantages and disadvantages of the various methods used to detect BRAF mutations.

Long noncoding RNA MALAT1 can serve as a valuable biomarker for prognosis and lymph node metastasis in various cancers: a meta-analysis

BackgroundMetastasis-associated lung adenocarcinoma transcript 1 (MALAT1), a newly discovered long intergenic noncoding RNA (lincRNA), has been reported to be aberrantly expressed in various cancers, and may serve as a novel potential biomarker for cancer prognosis. This meta-analysis was conducted to investigate the effects of MALAT1 on cancer prognosis and lymph node metastasis.MethodsA quantitative meta-analysis was performed using a systematic search of PubMed, Medline and Web of Science databases to identify eligible papers on prognostic value of MALAT1 in cancers. The pooled hazard ratios (HRs) or odds ratios (OR) with a 95 % confidence interval (95 % Cl) were calculated to evaluate its prognostic value.ResultsA total of 2094 patients from 17 studies between 2003 and 2016 were included. The results revealed that elevated MALAT1 expression was significantly associated with poor overall survival (OS) in 11 types of cancers (HR = 1.91, 95 % CI 1.49–2.34). Furthermore, subgroup analysis indicated that region of study (Germany, Japan or China), cancer type (digestive system cancers, urinary system cancers or respiratory system cancers) and sample size (more or less than 100) did not alter the significant predictive value of MALAT1 in OS from various types of cancer. In addition, upregulation of MALAT1 expression was significantly associated with poor disease-free survival (HR = 2.29, 95 % CI 1.24–3.35), and recurrence-free survival (HR = 2.09, 95 % CI 0.81–3.37). The results showed that the incidence of lymph node metastasis was higher in high MALAT1 expression group than that in low MALAT1 expression group (OR = 1.67, 95 % CI 1.30–2.15).ConclusionsThis meta-analysis revealed that elevated MALAT1 expression may serve as a novel predictive biomarker for poor survival and lymph node metastasis in different types of cancer.

Interleukin-5 facilitates lung metastasis by modulating the immune microenvironment.

Although the lung is the most common metastatic site for cancer cells, biologic mechanisms regulating lung metastasis are not fully understood. Using heterotopic and intravenous injection models of lung metastasis in mice, we found that IL5, a cytokine involved in allergic and infectious diseases, facilitates metastatic colonization through recruitment of sentinel eosinophils and regulation of other inflammatory/immune cells in the microenvironment of the distal lung. Genetic IL5 deficiency offered marked protection of the lungs from metastasis of different types of tumor cells, including lung cancer, melanoma, and colon cancer. IL5 neutralization protected subjects from metastasis, whereas IL5 reconstitution or adoptive transfer of eosinophils into IL5-deficient mice exerted prometastatic effects. However, IL5 deficiency did not affect the growth of the primary tumor or the size of metastatic lesions. Mechanistic investigations revealed that eosinophils produce CCL22, which recruits regulatory T cells to the lungs. During early stages of metastasis, Treg created a protumorigenic microenvironment, potentially by suppressing IFNγ-producing natural killer cells and M1-polarized macrophages. Together, our results establish a network of allergic inflammatory circuitry that can be co-opted by metastatic cancer cells to facilitate lung colonization, suggesting interventions to target this pathway may offer therapeutic benefits to prevent or treat lung metastasis.