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Tumour Invasion (tumour + invasion)
Selected AbstractsMetalloproteinase expression in normal and malignant oral keratinocytes: stimulation of MMP-2 and -9 by scatter factorEUROPEAN JOURNAL OF ORAL SCIENCES, Issue 4 2000J. H. Bennett Matrix metalloproteinases (MMPs) are Zn2+ dependent proteases produced by a variety of cell types. They have a fundamental role in tissue remodelling, tumour invasion and metastasis. Scatter factor (SF), secreted by fibroblasts, has a paracrine action on epithelial cells and binds the trans-membrane c-met receptor inducing loss of adhesion, cell motility and invasiveness in vitro. The purpose of this study was to test if SF can regulate the production of MMPs by epithelial cells. Supernatants from oral squamous cell carcinoma-derived cells (H375 and H376), a human keratinocyte line (UP), and primary cultures of oral mucosal keratinocytes, grown in the presence or absence of SF, were analysed using 0.1% gelatin zymography. MMPs were characterised by comparison with human recombinant enzymes and by the use of specific inhibitors. Oral mucosal keratinocytes, UP, and H357 cells expressed MMP-2 and MMP-9, whilst H376 cells only expressed MMP-2. SF increased the expression of MMP-9 in UP and MMP-2 in H376 supernatants. Both MMP-2 and MMP-9 activity were increased in H357 and normal keratinocyte supernatants. This could be blocked using a human recombinant anti-SF antibody. In all epithelial lines tested, c-Met, the cell surface receptor for SF, could be detected. The results indicate that SF stimulates MMP expression in UP, H376, H357, and normal oral mucosal cells and points to a role for SF in the regulation of oral keratinocyte behaviour in wound healing and neoplasia. [source] Expression of matrix metalloproteinases MMP-2, MMP-9 and their tissue inhibitors TIMP-1 and TIMP-2 in the epithelium and stroma of salivary gland pleomorphic adenomasHISTOPATHOLOGY, Issue 3 2009Xiaojun Zhang Aims:, The balance between matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) is involved in the morphogenesis of normal salivary gland as well as in the mechanisms of tumour invasion and metastasis. The role of MMPs and TIMPs in pleomorphic adenoma has not been elucidated sufficiently. Our aim was to analyse the mRNA and protein expression of MMP-2, MMP-9, TIMP-1 and TIMP-2 in the epithelium and stroma of pleomorphic adenoma and to evaluate their roles. Methods and results:, In each sample from six patients, cells from the epithelium and stroma were obtained by laser microdissection. The mRNA expression of MMPs and TIMPs was determined by real-time quantitative reverse transcriptase-polymerase chain reaction and protein expression was confirmed by immunohistochemistry. Results showed that mRNA expression of MMPs and TIMPs was significantly higher in stroma than in epithelium in most patients. MMPs and TIMPs were immunoreactive mainly in epithelium rather than in stroma. Conclusions:, Our results provide preliminary evidence that stromal myoepithelium may be the primary source of MMPs and that the stroma has the potential to play a more important role than ductal epithelium in biological behaviour of pleomorphic adenomas. These findings seem worthy of further investigation. [source] Immunophenotypic features of MELF pattern invasion in endometrial adenocarcinoma: evidence for epithelial,mesenchymal transitionHISTOPATHOLOGY, Issue 1 2009Colin J R Stewart Aims:, Endometrial endometrioid adenocarcinomas (EEC) may show a distinctive morphological alteration characterized by the presence of microcystic, elongated and fragmented (,MELF') glands. These changes share features of epithelial,mesenchymal transition (EMT) in carcinomas arising at other sites. The aim was to compare the immunophenotypic profile of MELF-type epithelium with conventional glandular areas of EEC. Methods and results:, Twenty-one EEC were stained immunohistochemically for cytokeratin (CK) AE1/AE3, CK7, vimentin, oestrogen receptor, progesterone receptor and E-cadherin. Conventional tumour glands usually showed preserved membranous E-cadherin immunoreactivity with peripheral accentuation of vimentin and hormone receptor expression. MELF-type invasion was characterized by strong CK7 expression, sometimes in contrast to adjacent unstained tumour glands. MELF areas were usually negative for hormone receptors and showed reduced E-cadherin expression. Conclusions:, The expression of hormone receptors and intermediate filaments shows specific distribution patterns within EEC. MELF pattern invasion shows an altered immunophenotype compared with conventional glandular tumour areas. These findings suggest that MELF-type invasion represents a specific tumour alteration, and the reduction in hormone receptor and E-cadherin expression would be consistent with EMT. Immunohistochemical studies of EEC should consider micro anatomical variations in immunoreactivity, since these may be relevant to tumour invasion and progression. [source] Resection of hilar cholangiocarcinoma with left hepatectomy after pre-operative embolization of the proper hepatic arteryHPB, Issue 2 2010Yoshikazu Yasuda Abstract Background:, Right or right-extended hepatectomy including the caudate lobe is the most common treatment for hilar cholangiocarcinoma (HC). A 5-year survival of up to 60% can be achieved using this procedure if R0-resection is obtained. However, for some patients a left-sided liver resection is necessary to obtain radical resection. The close relationship between the right hepatic artery and the HC in these patients frequently limits the ability to achieve a radial R0-resection without difficult vascular reconstruction. The aim of the present study was to describe the outcome of patients who underwent pre-operative embolization of the proper hepatic artery in an effort to induce development of arterial collaterals thus allowing the resection of the proper and right hepatic artery without vascular reconstruction. Methods:, In patients presenting with HC who were considered to require a left hepatic lobectomy and in whom pre-operative work up revealed possible tumour invasion of the right hepatic artery, transcatheter arterial embolization (TAE) of the proper hepatic artery or the left and right hepatic arteries was performed. Three weeks later, a left-sided hepatectomy with resection of all portal structures except the portal vein was performed. Results:, In six patients, pre-operative embolization of the proper hepatic artery was performed. Almost instantaneously in all six patients arterial flow signals could be detected in the liver using Doppler ultrasonography. No patient died peri-operatively. In all six patients an R0 radial resection was achieved and in three an R0 proximal transection margin was obtained. All post-operative complications were managed successfully using percutaneous drainage procedures. No patient developed local recurrence and two patients remain disease free more than 7 years after surgery. Summary:, After pre-operative embolization of the proper hepatic artery, resection of the HC with left hepatectomy is a promising new approach for these technically demanding patients, giving them the chance of a cure. [source] Inhibition of tumour invasion and angiogenesis by epigallocatechin gallate (EGCG), a major component of green teaINTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 6 2001Young D. Jung Epidemiological studies have suggested that consumption of green tea may decrease cancer risk. In addition, abundant pre-clinical data from several laboratories have provided convincing evidence that polyphenols present in green tea afford protection against cancer in both in vivo and in vitro studies. Recently, epigallocatechin gallate (EGCG), a putative chemopreventive agent and a major component of green tea, was reported to inhibit tumour invasion and angiogenesis, processes that are essential for tumour growth and metastasis. Understanding the basic principles by which EGCG inhibits tumour invasion and angiogenesis may lead to the development of new therapeutic strategies, in addition to supporting the role of green tea as a cancer chemopreventive agent. [source] Invasive front grading: reliability and usefulness in the management of oral squamous cell carcinomaJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 1 2003Faleh A. Sawair Abstract Background:, The value of histological grading was examined with emphasis on reliability of assessment in 102 cases of intraoral squamous cell carcinoma from Northern Ireland with known outcome. Methods:, Two pathologists independently graded the invasive tumour front blinded to the stage and outcome. Results:, Intraobserver agreement was acceptable but interobserver agreement was not satisfactory. The degree of keratinisation was assessed most consistently while nuclear polymorphism was the least reliable feature. Multivariate survival analysis showed that the total grading score was associated with overall survival while the pattern of tumour invasion was the most valuable feature in estimating regional lymph node involvement. The number of positive lymph nodes was strongly associated with regional relapse, while the treatment modality and status of the surgical margins correlated with local relapse. Conclusions:, Grading of selected features in OSCC is reliable and can facilitate treatment planning. [source] Outcome following removal of canine spindle cell tumours in first opinion practice: 104 casesJOURNAL OF SMALL ANIMAL PRACTICE, Issue 11 2009D. Chase Objectives:To define the outcome of a cohort of canine patients with a histological diagnosis of spindle cell tumour of soft tissue managed solely by surgery in first opinion practice. Methods:Clinical details of 104 spindle cell sarcomas submitted to Finn Pathologists during the year 2000 were reviewed. Questionnaires were sent to the submitting veterinarians, requesting details about the tumour, surgery performed and ultimate outcome of the patient. Results:The method of surgical resection was described as marginal in 45 dogs (44·2 per cent). Excision margins of 3 cm or more were described in less than 10 per cent of cases. Tumours recurred locally in 29 dogs (27·9 per cent). Eighteen dogs (21·7 per cent) died of tumour-related causes. Most deaths were unrelated to sarcoma (50 dogs, 60·2 per cent) or unknown (15 dogs, 18 per cent). The median survival time was 1013 days. Tumour size, location or degree of surgical resection were not significantly related to survival or tumour recurrence. A palpable assessment of tumour invasion into underlying tissues was significantly associated with decreased disease-free interval (P<0·0001) and survival time (P = 0·0070). Clinical Significance:The results of this retrospective study indicate that many spindle cell tumours managed in first opinion practice exhibit a low-grade biological behaviour and may respond well to more conservative surgery than current recommendations advise. [source] Oestrogenic Steroids and Melanoma Cell Interaction with Adjacent Skin Cells Influence Invasion of Melanoma Cells In VitroPIGMENT CELL & MELANOMA RESEARCH, Issue 2000SHEILA MAC NEIL The invasion of melanoma is complex and multi-staged and involves changes in both cell/extracellular matrix (ECM) and cell/cell interactions. Female steroids and ,-MSH have also been reported to influence metastatic melanoma progression, but their mechanisms of action are unknown. Accordingly, our aim was to establish in vitro models to examine (a) the influence of sex steroids and ,-melanocyte-stimulating hormone (,-MSH) on tumour invasion and the influence of (b) ECM proteins and (c) adjacent cells on melanoma invasion. In the first model, melanoma cell invasion through fibronectin over 20 hr under serum-free conditions was used to investigate the effects of 17,-oestradiol and oestrone on the invasion of human melanoma cell lines, A375-SM and HBL. A375-SM, but not HBL cells, proved very susceptible to inhibition by female steroids. However, invasion of the HBL line was inhibited by ,-MSH. Using the second model of reconstructed human skin based on de-epidermised acellular dermis, we found that the HBL cells on their own failed to invade into the dermis (irrespective of the presence or absence of the basement membrane). However, there was a significant synergistic interaction between keratinocytes, fibroblasts and HBL cells, such that a modest invasion of HBLs into the dermis was seen within 2 weeks when other skin cells were present. In contrast, A375-SM cells showed a significant ability to invade the dermis in the absence of other cells, with less invasion when other skin cells were present. In summary, these models have provided new information on the extent to which melanoma cell invasion is sensitive to oestrogenic steroids and to ,-MSH and to interaction, not only with adjacent skin cells but also to the presence of basement membrane antigens. [source] The role of annexins in tumour development and progression,THE JOURNAL OF PATHOLOGY, Issue 2 2008S Mussunoor Abstract The annexins are a super-family of closely related calcium and membrane-binding proteins. They have a diverse range of cellular functions that include vesicle trafficking, cell division, apoptosis, calcium signalling and growth regulation. Many studies have shown the annexins to be among the genes whose expression are consistently differentially altered in neoplasia. Some annexins show increased expression in specific types of tumours, while others show loss of expression. Mechanistic studies relating the changes in annexin expression to tumour cell function, particularly tumour invasion and metastasis, angiogenesis and drug resistance, are now also emerging. Changes in the expression of individual annexins are associated with particular types of tumour and hence the annexins may also be useful biomarkers in the clinic. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] Co-localization of multiple ErbB receptors in stratified epithelium of oral squamous cell carcinomaTHE JOURNAL OF PATHOLOGY, Issue 3 2001Roberto Bei Abstract The expression of all four ErbB receptors was compared by immunohistochemistry, using receptor-specific polyclonal antisera, in 32 invasive, 11 in situ carcinomas, six benign lesions, and 22 samples of histologically normal mucosa adjacent to specimens of carcinoma originating from oral cavity epithelium. Among invasive and in situ carcinoma, EGFR expression was the most prevalent (in 29/32 and 8/11 cases, respectively) followed by ErbB2 (17/32 and 2/11) and ErbB4 (9/32 and 1/10), while ErbB3 was only detected in invasive tumours (12/32). Specific patterns included invasive tumours with expression of EGFR (8/32) or ErbB4 (1/32) alone, as well as different receptor combinations (EGFR+ErbB2, EGFR+ErbB4, EGFR+ErbB2+ErbB3, EGFR+ErbB2+ErbB4, and all four receptors). Simultaneous expression of three or four ErbB receptors correlated with tumour invasion (p=2.2×10,4) and localized in the intermediate epithelial cell layer of well and moderately differentiated tumours. No other significant correlation with clinico-pathological features was noticed. Some benign lesions and histologically normal mucosa adjacent to carcinomas showed weak immunostaining of EGFR (10/28), ErbB2 (4/28) or ErbB4 (3/28). By comparison, overexpression, as indicated by increased staining intensity, was observed in invasive tumours for EGFR (18/32), ErbB2 (8/32), ErbB4 (3/32), and ErbB3 (3/32). Statistical evaluation demonstrated a significant association of EGFR or ErbB2 overexpression with invasive carcinoma when compared with benign lesions and apparently normal epithelium (p=5.2×10,7 and p=5×10,3, respectively). Tumour-specific overexpression of ErbB receptors and their co-expression, most frequently involving EGFR and ErbB2, in the same cell layer of neoplastic epithelium, implicate receptor heterodimers in the pathogenesis of oral squamous carcinoma. Copyright © 2001 John Wiley & Sons, Ltd. [source] The invasive behaviour of prostatic cancer cells is suppressed by inhibitors of tyrosine kinase,APMIS, Issue 1 2006HAAKON SKOGSETH Proteolytic enzymes, and especially urokinase plasminogen activator (uPA), play an important role in tumour invasion and metastasis. Previously we demonstrated that the production of urokinase plasminogen activator (uPA) was decreased by several tyrosine kinase inhibitors (TKI) in two prostatic carcinoma cell lines. The effect of the two TKI genistein and tyrphostin AG-1478 was investigated in the prostate carcinoma cell lines PC-3 and DU-145. A reconstituted basal lamina (Matrigel) was used as a migration barrier. The production of matrix metalloproteinases (MMP) was also measured. Roles of plasminogen and uPA were examined. Cell invasion was increased by plasminogen, but this enhanced cell migration was counteracted by TKI treatment. The increased cell invasion induced by plasminogen was decreased by at least 60% in both cell lines when ,-2 anti-plasmin was added to the assay. Cells in the absence of plasminogen were not affected by TKI. External uPA failed to regenerate the decreased cell invasion caused by TKI. The production of MMP was inhibited by both TKI. Our results indicate a possible role of TKI as inhibitors of cancer cell invasion by inhibiting uPA and MMP production. [source] Renal oncocytoma: a clinicopathological analysis of 45 consecutive casesBJU INTERNATIONAL, Issue 9 2005Tomas Gudbjartsson OBJECTIVE To evaluate the clinical behaviour and pathology of renal oncocytoma in a well-defined population over a 30-year period. PATIENTS AND METHODS In a retrospective population-based study we assessed relevant clinical and pathological factors in 45 patients (31 men and 14 women) diagnosed with renal oncocytoma in Iceland between 1971 and 2000. Clinical presentation, pathology, survival and causes of death were evaluated. RESULTS The age-standardized incidence was 0.3 per 100 000 per year for both men and women, the incidence of oncocytomas being 5.5% of renal cell carcinomas (RCCs) diagnosed during the same period in Iceland. Fourteen patients were diagnosed at autopsy for an unrelated disease. Of 31 living patients (mean age 70.5 years), seven were diagnosed incidentally (23%), and the others had presented with haematuria (32%), abdominal pain (29%), and weight loss (10%). All the patients had a radical nephrectomy, except for one with bilateral oncocytoma who had a partial nephrectomy. The mean (range) tumour size was 5.7 (0.9,12) cm. Eighteen patients (58%) were diagnosed at Tumour-Node-Metastasis stage I, 10 at stage II (32%) and three at stage III (10%), all of those at stage III having renal capsular penetration or tumour invasion into perirenal fat tissue (T3aN0M0). No patients were diagnosed with lymph node or distant metastasis. Two cases of coexisting RCC were detected. After a median follow-up of 8.3 years there were no recurrences or deaths from oncocytoma (100% disease-specific survival). The overall 5-year survival was 63%, with most patients dying from cardiovascular diseases or nonrenal cancers. CONCLUSIONS In most cases renal oncocytoma behaves like a benign tumour; the long-term prognosis is excellent. Thus, in the present patients, radical nephrectomy could be regarded as an over-treatment and nephron-sparing surgery as more appropriate, especially in patients with small tumours. However, both coexisting RCC and perirenal fat invasion, a hallmark of malignant behaviour, might indicate that more radical surgery is warranted in some of these patients. [source] The relationship between angiogenesis and cyclooxygenase-2 expression in prostate cancerBJU INTERNATIONAL, Issue 1 2005Rono Mukherjee OBJECTIVE To test the hypothesis that angiogenesis in prostate cancer is associated with tumour invasion and metastasis, and that this is mediated through increased cyclooxygenase-2 (COX-2) expression. PATIENTS AND METHODS Angiogenesis was assessed in 105 patients with either prostate cancer (79) or benign prostatic hyperplasia (BPH, 26) and these data correlated with levels of COX-2 expression in the same dataset. The mean microvessel density (MVD) was analysed as a marker of angiogenesis, using the endothelial antigen CD34 stained by immunohistochemistry. RESULTS There was no difference in MVD in progressive tumour stages compared with BPH. There was a negative correlation between MVD and COX-2 expression, but the effect of increased COX-2 expression on MVD was not marked. CONCLUSION These data suggest that COX-2 drives tumour spread in prostate cancer by means other than the promotion of angiogenesis. [source] Vitamin D and systemic cancer: is this relevant to malignant melanoma?BRITISH JOURNAL OF DERMATOLOGY, Issue 2 2002J.E. Osborne Summary 1,25-dihydroxyvitamin D3[1,25(OH)2D3] is a well-known potent regulator of cell growth and differentiation and there is recent evidence of an effect on cell death, tumour invasion and angiogenesis, which makes it a candidate agent for cancer regulation. The classical synthetic pathway of 1,25(OH)2D3 involves 25- and 1,-hydroxylation of vitamin D3, in the liver and kidney, respectively, of absorbed or skin-synthesized vitamin D3. There is recent focus on the importance in growth control of local metabolism of 1,25(OH)2D3, which is a function of local tissue synthetic hydroxylases and particularly the principal catabolizing enzyme, 24-hydroxylase. The classical signalling pathway of 1,25(OH)2D3 employs the vitamin D nuclear receptor (VDR), which is a transcription factor for 1,25(OH)2D3 target genes. Effects of this pathway include inhibition of cellular growth and invasion. Cytoplasmic signalling pathways are increasingly being recognized, which similarly may regulate growth and differentiation but also apoptosis. 1,25(OH)2D3 has a major inhibitory effect on the G1/S checkpoint of the cell cycle by upregulating the cyclin dependent kinase inhibitors p27 and p21, and by inhibiting cyclin D1. Indirect mechanisms include upregulation of transforming growth factor-, and downregulation of the epidermal growth factor receptor. 1,25(OH)2D3 may induce apoptosis either indirectly through effects on the insulin-like growth receptor and tumour necrosis factor-, or more directly via the Bcl-2 family system, the ceramide pathway, the death receptors (e.g. Fas) and the stress-activated protein kinase pathways (Jun N terminal kinase and p38). Inhibition of tumour invasion and metastasis potential has been demonstrated and mechanisms include inhibition of serine proteinases, metalloproteinases and angiogenesis. The lines of evidence for an effect of vitamin D3 in systemic cancer are the laboratory demonstration of relevant effects on cellular growth, differentiation, apoptosis, malignant cell invasion and metastasis; epidemiological findings of an association of the occurrence and outcome of cancers with derangements of vitamin D3/1,25(OH)2D3 and the association of functional polymorphisms of the VDR with the occurrence of certain cancers. In addition, vitamin D3 analogues are being developed as cancer chemotherapy agents. There is accumulating evidence that the vitamin D3/1,25(OH)2D3/VDR axis is similarly important in malignant melanoma (MM). MM cells express the VDR, and the antiproliferative and prodifferentiation effects of 1,25(OH)2D3 have been shown in cultured melanocytes, MM cells and MM xenografts. Recently, an inhibitory effect on the spread of MM cells has been demonstrated, low serum levels of 1,25(OH)2D3 have been reported in MM patients and the VDR polymorphisms have been shown to be associated with both the occurrence and outcome of MM. The relationship between solar irradiation and MM is more complex than for the systemic cancers. As in other cancers, there is evidence of a protective effect of vitamin D3 in MM, but ultraviolet radiation, which is a principal source of vitamin D3, is mutagenic. Further work is necessary on the influence of serum vitamin D3 levels on the occurrence and prognosis of MM, the effects of sun protection measures on serum vitamin D3 levels in temperate climates and epidemiological studies on geographical factors and skin type on the prognosis of MM. Meanwhile, it would seem mandatory to ensure an adequate vitamin D3 status if sun exposure were seriously curtailed, certainly in relation to carcinoma of breast, prostate and colon and probably also MM. [source] A predictive model for local recurrence after transanal endoscopic microsurgery for rectal cancer,,BRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 3 2009S. P. Bach Background: The outcome of local excision of early rectal cancer using transanal endoscopic microsurgery (TEM) lacks consensus. Screening has substantially increased the early diagnosis of tumours. Patients need local treatments that are oncologically equivalent to radical surgery but safer and functionally superior. Methods: A national database, collated prospectively from 21 regional centres, detailed TEM treatment in 487 subjects with rectal cancer. Data were used to construct a predictive model of local recurrence after TEM using semiparametric survival analyses. The model was internally validated using measures of calibration and discrimination. Results: Postoperative morbidity and mortality were 14·9 and 1·4 per cent respectively. The Cox regression model predicted local recurrence with a concordance index of 0·76 using age, depth of tumour invasion, tumour diameter, presence of lymphovascular invasion, poor differentiation and conversion to radical surgery after histopathological examination of the TEM specimen. Conclusion: Patient selection for TEM is frequently governed by fitness for radical surgery rather than suitable tumour biology. TEM can produce long-term outcomes similar to those published for radical total mesorectal excision surgery if applied to a select group of biologically favourable tumours. Conversion to radical surgery based on adverse TEM histopathology appears safe for p T1 and p T2 lesions. Copyright © 2009 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [source] Role of magnetic resonance imaging in the diagnosis and single-stage surgical resection of invasive lobular carcinoma of the breast,BRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 10 2002K. Munot Background: Conventional imaging with mammography and ultrasonography has a low sensitivity for diagnosis and a tendency to underestimate the extent of invasive lobular carcinoma (ILC) of the breast. The aim was to determine whether magnetic resonance imaging (MRI) had any advantages for the characterization of ILC. Methods: Twenty patients with histologically proven ILC underwent preoperative imaging with MRI. MRI was performed to aid detection of malignancy in six patients with a clinically suspicious presentation but normal or indeterminate imaging on mammography and ultrasonography. In 14 patients MRI was performed to determine tumour extent. Results: MRI accurately identified malignancy in five of six patients with normal or indeterminate conventional imaging. In seven of 14 patients in whom MRI was performed to determine tumour extent, it provided significant additional information. These included four patients in whom conventional imaging grossly underestimated tumour size, two patients in whom MRI identified an unsuspected contralateral breast tumour and one patient in whom MRI predicted tumour invasion of the pectoral muscle. The correlation between tumour size on histological examination was better with MRI (r = 0·967) than with mammography (r = 0·663) and ultrasonography (r = 0·673). Conclusion: MRI can provide considerable additional information in the detection and characterization of ILC. © 2002 British Journal of Surgery Society Ltd [source] | ||||||||||||||||||||||