Human tumor cell heterogeneity and metastasis.

Spremulli, Ellen N.; Dexter, Daniel L.

doi:10.1200/jco.1983.1.8.496

Cited by 90 publications

(34 citation statements)

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“…The metastatic cascade is a complex series of processes including angiogenesis, intravasation of tumor cells, transport by the circulation, adhesive interaction with endothelial cells, extravasation, and colonization of the target organ (38)(39)(40)(41). Only a small subpopulation of cells from heterogeneous primary tumors appears able to form metastatic colonies (42,43). The survival and proliferation of these metastatic cells depend on various biological properties, such as resistance to host defense mechanisms, regulation of adhesion molecules, and enzymes that degrade basement membranes (39,40,43,44).…”

Section: Discussionmentioning

confidence: 99%

Expression of Fas ligand in liver metastases of human colonic adenocarcinomas

Shiraki

Tsuji

Shioda

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

237

173

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Fas ligand (FasL) plays a pivotal role in lymphocyte cytotoxicity and the maintenance of immunological homeostasis. Since FasL has been implicated in the existence of immunologically privileged body sites by inducing apoptosis of activated T lymphocytes, we investigated the expression of FasL in human colon cancers. We found that two out of seven primary tumors and all four hepatic metastatic tumors of surgically obtained colonic adenocarcinoma expressed FasL mRNA and protein, detected by reverse transcription-coupled PCR and by immunohistochemical staining, respectively. Expression of FasL was not detected in normal colonic epithelial cells. FasL mRNA was also expressed in some human colonic adenocarcinoma cell lines including SW480, SW1116, and LS180 cells. Cell-surfaceassociated FasL was detected in these human colon cancer cells by f luorescence immunocytochemical staining. In addition, the expressed FasL was demonstrated to be functional, since coculture experiments using FasL-expressing SW480 cells resulted in apoptosis of Jurkat T leukemia cells that are sensitive to Fas-mediated apoptosis, and this process was specifically inhibited by the neutralizing anti-human FasL antibody. Thus, our findings and other data suggest an alternative mechanism that enables tumors to evade immune destruction by inducing apoptosis in activated T lymphocytes. Furthermore, constitutive expression of FasL in hepatic metastatic tumors suggests that FasL may also be important in their colonization in the liver through induction of apoptosis in the surrounding Fas-expressing hepatocytes.

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Section: Discussionmentioning

confidence: 99%

Expression of Fas ligand in liver metastases of human colonic adenocarcinomas

Shiraki

Tsuji

Shioda

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

237

173

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“…This seems to be due to the undifferentiated component of the histology. The median number of removed pelvic LNs was 16 (range, [15][16][17][18][19][20][21][22][23][24][25][26][27], the median number of removed para-aortic LNs was 8 (range, 4-30), and the median number of positive paraaortic LNs was 1 (range, 1-4). All patients had FIGO stage IIIC2 disease.…”

Section: Resultsmentioning

confidence: 99%

“…19 Tumor cells first develop the capacity for local tissue invasion and then spread through gaps between endothelial cells into the lymph-vascular space of the stroma, and, once LVSI has occurred, tumor cells have the potential for metastatic spread to other sites. 20 LVSI may lead to tumor emboli invading pelvic and para-aortic LNs. Previous investigators suggested that LVSI and other factors correlated significantly with para-aortic LNM.…”

Section: Discussionmentioning

confidence: 99%

Lymph-Vascular Space Invasion as a Significant Risk Factor for Isolated Para-aortic Lymph Node Metastasis in Endometrial Cancer: A Study of 203 Consecutive Patients

et al. 2010

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Background. The purpose of this study was to investigate various pathologic risk factors associated with para-aortic lymph node metastasis (LNM) in surgically staged patients with endometrial cancer. Materials and Methods. We performed a retrospective analysis of 203 consecutive patients with endometrial cancer who were surgically staged from 2000 to 2009. The association among the various pathologic variables for para-aortic LNM was determined with univariate and multivariate analyses. Results. Of 203 patients, 29 patients (14.3%) had LNM. Also, 10 patients (4.9%) had only pelvic LNM, 14 (6.9%) had both pelvic and para-aortic LNM, and 5 (2.5%) had para-aortic LNM without pelvic LN involvements. Histologic type (P = .001), tumor grade (P \ .001), tumor size (P = .003), depth of myometrial invasion (P \ .001), cervical invasion (P \ .001), parametrial invasion (P = .002), lymph-vascular space invasion (LVSI) (P \ .001), serosal/ adnexal invasion (P \ .001), positive cytology (P = .002), peritoneal seeding (P \ .001), and pelvic LNM (P \ .001) were significant pathologic factors for para-aortic LNM. On multivariate analysis, cervical invasion (P = .032), LVSI (P = .018), and positive pelvic LNs (P = .002) were independent factors for para-aortic LNM. With regard to isolated para-aortic LNM, tumor grade (P = .017) and LVSI (P = .002) were significant factors for LN involvements. On multivariate analysis, LVSI (P = .004) was the only significant independent factor. Conclusions. LVSI correlates significantly with the risk of isolated para-aortic LNM in endometrial cancer patients.Lymph node metastasis (LNM) is one of the important prognostic factors in endometrial cancer. The Gynecologic Oncology Group (GOG) published two large surgicalpathological studies of women with clinical stage I or II endometrial cancer.1,2 A substantial number of patients with clinical stage I disease (22%) had extrauterine disease, and tumor grade, depth of myometrial invasion, cervical invasion, vascular space invasion, positive cytology, adnexal involvement, and certain histologic types were found to be risk factors for pelvic and para-aortic LNM. Based on these results, the International Federation of Gynecology and Obstetrics (FIGO) adopted a surgical staging system to replace the clinical staging system in 1988.3 FIGO stage IIIC disease meant pelvic or para-aortic LN involvement. Several studies demonstrated that stage IIIC disease had diversity in the prognosis and patients with para-aortic LNM had poorer survival than those with negative paraaortic LNs.2,4-8 Recently, the FIGO revised the surgical staging system. 9 Stage IIIC disease was divided into two categories of IIIC1 with positive pelvic LNs and IIIC2 with positive para-aortic LNs, irrespective of the status of pelvic LNs status.Para-aortic LNM occurs mainly by way of pelvic LNM.4,10 However, direct spread to para-aortic LNs via ovarian vessels is a possible route of lymphatic spread, and patients have isolated para-aortic LNM without positive pelvic LNs. [10][11][12] ...

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“…In its simplest model, a solid tumor may be viewed as an organ containing multiple cell types that act in concert to promote tumor growth [Spremulli andDexter, 1983, Dexter et al, 1978]. Thus, drugs that target a single type of cell for therapeutic intervention may only provide marginal anti-tumor effect.…”

Section: Introductionmentioning

confidence: 98%

Colloidal gold nanoparticles: a novel nanoparticle platform for developing multifunctional tumor‐targeted drug delivery vectors

Paciotti

Kingston

Tamarkin

2006

Drug Development Research

424

264

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Nanotechnology applied to biological problems represents an emerging field with the potential to offer extremely sensitive diagnostics and targeted cancer therapies. However, to achieve these goals, nanoparticle delivery systems must outwit the many barriers that are intrinsic to the body's defenses, as well as those that develop during the growth and progression of tumors. The science is advancing and, for example, true nanoscale tumor-targeted drug delivery vectors are now able to reduce the likelihood of opsonization in the bloodstream and uptake by the reticuloendothelial system. Other advances hold promise for delivering multiple therapeutic agents to non-homogeneous populations of cancer cells in solid tumors. We briefly summarize herein our attempts to build such multifunctional nanotherapeutics using colloidal gold nanoparticles. Specifically we discuss the development of colloidal gold-based drugs that are designed to target the delivery of TNF and paclitaxel to solid tumors. Drug Dev. Res. 67:47-54, 2006.

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Human tumor cell heterogeneity and metastasis.

Cited by 90 publications

References 0 publications

Expression of Fas ligand in liver metastases of human colonic adenocarcinomas

Expression of Fas ligand in liver metastases of human colonic adenocarcinomas

Lymph-Vascular Space Invasion as a Significant Risk Factor for Isolated Para-aortic Lymph Node Metastasis in Endometrial Cancer: A Study of 203 Consecutive Patients

Colloidal gold nanoparticles: a novel nanoparticle platform for developing multifunctional tumor‐targeted drug delivery vectors

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