Cancer Metastasis: Building a Framework

Gupta, Gaorav P.; Massagué, Joan

doi:10.1016/j.cell.2006.11.001

Cited by 3,784 publications

(3,131 citation statements)

References 104 publications

Supporting

Mentioning

3,073

Contrasting

Unclassified

Order By: Relevance

“…Circulating tumor cells (CTCs) are cells that flow into blood vessels or lymphatics from the primary tumor to circulate through the whole body. (27,28) CTCs are found at 1-10 cells per 1 mL of whole blood in patients with metastatic disease; 0.01% of CTCs detached from the primary tumor form metastases. (29,30) In the present study, no difference in prognosis based on GRWR was found among patients with HCC within the Milan criteria, whereas a significant increase in recurrence rates and a decrease in survival rates were observed in patients with HCC beyond the Milan criteria who received SFSG.…”

Section: Discussionmentioning

confidence: 99%

Small‐for‐size grafts increase recurrence of hepatocellular carcinoma in liver transplantation beyond milan criteria

et al. 2017

View full text Add to dashboard Cite

Living donor liver transplantation (LDLT) has been reported to have high rates of hepatocellular carcinoma (HCC) recurrence compared with deceased donor liver transplantation (DDLT). This has been assumed to be due to the frequent use of small-for-size grafts (SFSGs) in LDLT rather than DDLT, but the relationship between graft size and prognosis remains controversial. This study aimed to clarify the effect of SFSGs on the oncologic outcomes of patients with HCC who underwent LDLT. Between January 2005 and December 2015, 597 consecutive patients underwent LDLT. Among these patients, those with HCC who underwent LDLT were randomly matched at a 1:3 ratio (graft-to-recipient body weight ratio [GRWR] < 0.8%:GRWR > 0.8%) according to propensity score. HCC recurrence and patient survival were analyzed using the Kaplan-Meier method and log-rank test. In addition, stratified subgroup analysis based on the Milan criteria was performed. SFSG was defined as a GRWR < 0.8%. Using propensity score matching, 82 patients with GRWR < 0.8% and 246 patients with GRWR 0.8% were selected. For patients with HCC within the Milan criteria, no significant difference of HCC recurrence (P 5 0.82) and patient survival (P 5 0.95) was found based on GRWR. However, for patients with HCC beyond the Milan criteria, 1-, 3-, and 5-year recurrence-free survival rates were 52.4%, 49.3%, and 49.3%, respectively, for patients with GRWR < 0.8%, and 76.5%, 68.3%, and 64.3%, respectively, for patients with GRWR 0.8% (P 5 0.049). The former group exhibited poor patient survival rates (P 5 0.047). In conclusion, for patients with HCC within the Milan criteria, no significant difference in oncologic outcomes was found based on liver graft size. However, among the patients with HCC beyond the Milan criteria, SFSG recipients showed poor oncologic outcomes. Because extended criteria are frequently used in LDLT for HCC, a recipient's prognosis can be improved if a liver graft of appropriate size is carefully selected during donor selection. Liver Transplantation 24 35-43 2018 AASLD.Received May 24, 2017; accepted August 27, 2017. Although living donor liver transplantation (LDLT) was initiated because of the shortage of deceased donor livers, it was accepted as an established method of treatment for end-stage liver diseases in the 1990s. The first LDLT was performed to transplant the left lateral section of the liver from a mother to a child with biliary atresia in 1989. (1)(2)(3) After the mid-1990s, right lobe LDLT started to be performed on adult recipients with high metabolic demands, and significant improvements in the outcomes were observed.A major limitation of LDLT is the size of the liver graft that can be obtained safely from living donors. Small-for-size grafts (SFSGs) cannot appropriately deal with the portal flow in the recipient due to decreased liver volume. Shear stress caused by transient portal hypertension can cause acute mechanical injury, which then induces severe inflammatory responses to negatively affect the outcomes of liver transpla...

show abstract

Section: Discussionmentioning

confidence: 99%

Small‐for‐size grafts increase recurrence of hepatocellular carcinoma in liver transplantation beyond milan criteria

et al. 2017

View full text Add to dashboard Cite

show abstract

“…However, the importance of tumorstromal interactions in cancer progression is increasingly recognized and it is possible that factors secreted by reactive cellular elements may help propagate tumor invasion. 40 The interpretation of p16 immunoreactivity in endometrial cancer is problematic as it is not always clear whether a 'positive' or 'negative' staining reaction represents the abnormal finding. In gynecological pathology generally, p16 immunostaining has been used most widely as an adjunct to diagnosis in cervical biopsy specimens.…”

Section: Endometrial Carcinoma Invasionmentioning

confidence: 99%

Expression of cell cycle regulatory proteins in endometrial adenocarcinoma: variations in conventional tumor areas and in microcystic, elongated and fragmented glands

et al. 2009

View full text Add to dashboard Cite

Endometrial adenocarcinomas may show a distinctive pattern of invasion characterized by the presence of microcystic, elongated and fragmented glands, often most evident along the advancing tumor margin. Earlier, we have shown that these changes appear restricted to low-grade endometrioid carcinomas, many of which show focal mucinous differentiation and lymphovascular space invasion. However, the molecular alterations associated with this morphological alteration are not known. In this study, we have examined immunoreactivity for the cell cycle regulatory proteins cyclin D1, p16 and b-catenin in 22 endometrial carcinomas, specifically comparing the results in conventional tumor areas and in foci in which the glands exhibited microcystic, elongated and fragmented appearances. The conventional neoplastic glands exhibited cyclin D1 and p16 expression in most cases, with 450% tumor cells positive in 8 cases and 11 tumors, respectively. Membranous expression of b-catenin was usually preserved, with variable cytoplasmic and nuclear staining. Cyclin D1 and b-catenin predominantly stained cells at the peripheral or basal aspect of the conventional glands, whereas p16 was more uniformly expressed centrally. Tumor foci composed of microcystic, fragmented and elongated glands showed strong expression of cyclin D1 and p16, sometimes in contrast to unstained contiguous or adjacent conventional neoplastic elements, and there was also loss or fragmentation of membranous b-catenin staining. Intravascular tumor cells also expressed cyclin D1 and p16 and therefore the immunostains often highlighted subtle foci of lymphovascular invasion. The heterogenous expression of cell cycle regulatory proteins within endometrial adenocarcinoma illustrates the importance of assessing microanatomical variations in immunoreactivity, particularly at the advancing margin of tumors. The upregulation of cyclin D1 and p16, together with loss of membranous b-catenin expression in microcystic, fragmented and elongated glands, is similar to epithelial-mesenchymal transitions observed in other malignancies and suggests that this pattern of invasion represents an active rather than a degenerative cellular process. Modern Pathology (2009) 22, 725-733; doi:10.1038/modpathol.2009 published online 6 March 2009 Keywords: endometrial; carcinoma; invasion; MELF; epithelial-mesenchymal transition; immunohistochemistry Endometrial carcinomas can be divided into two major groups on the basis of clinicopathological, immunohistological and molecular features. 1,2 The more common (type 1) subgroup accounts for 80-85% of cases and mainly comprises endometrioid adenocarcinomas of low-to-intermediate grade. These tumors typically occur in perimenopausal and younger postmenopausal patients, often arise in hyperestrogenic states and are associated with atypical endometrial hyperplasia/endometrial intraepithelial neoplasia. Frequently, type 1 carcinomas are confined to the uterine corpus at the time of diagnosis (stage 1), and the prognosis in such patients is generally ...

show abstract

“…The development of metastases consists of a complex series of events accomplished by tumour cells after they acquire numerous abilities, one of which being the acquisition of an invasive potency. This mainly lies into an enhanced migration and the ability to digest the extracellular matrix (Gupta and Massague, 2006). Cell migration involves dynamic cytoskeletal changes and is highly regulated by the intracellular concentration of calcium.…”

Section: Introductionmentioning

confidence: 99%

P2X7 receptor activation enhances SK3 channels- and cystein cathepsin-dependent cancer cells invasiveness

et al. 2011

View full text Add to dashboard Cite

ATP-gated P2X 7 receptors (P2X 7 R) are unusual plasma membrane ion channels that have been extensively studied in immune cells. More recently, P2X 7 R have been described as potential cancer cell biomarkers. However, mechanistic links between P2X 7 R and cancer cell processes are unknown. Here, we show, in the highly aggressive human breast cancer cell line MDA-MB-435s, that P2X 7 receptor is highly expressed and fully functional. Its activation is responsible for the extension of neurite-like cellular prolongations, of the increase in cell migration by 35% and in cell invasion through extracellular matrix by 150%. The change in cancer cell morphology and the increased migration appeared to be due to the activation of Ca 2 þ -activated SK3 potassium channels. The enhanced invasion through the extracellular matrix was related to the increase of mature forms of cysteine cathepsins in the extracellular medium, which was independent of SK3 channel activity and not associated with cell death. Pharmacological targeting of P2X 7 R in vivo was crucial for cell invasiveness in a zebrafish model of metastases. Our results demonstrate a novel mechanistic link between P2X 7 R functionality in cancer cells and invasiveness, a key parameter in tumour growth and in the development of metastases. They also suggest a potential therapeutic role for the newly developed P2X 7 R antagonists.

show abstract

Cancer Metastasis: Building a Framework

Cited by 3,784 publications

References 104 publications

Small‐for‐size grafts increase recurrence of hepatocellular carcinoma in liver transplantation beyond milan criteria

Small‐for‐size grafts increase recurrence of hepatocellular carcinoma in liver transplantation beyond milan criteria

Expression of cell cycle regulatory proteins in endometrial adenocarcinoma: variations in conventional tumor areas and in microcystic, elongated and fragmented glands

P2X7 receptor activation enhances SK3 channels- and cystein cathepsin-dependent cancer cells invasiveness

Contact Info

Product

Resources

About