Ki67 antigen and PCNA proliferation markers predict survival in anorectal malignant melanoma

Ben‐Izhak, Ofer; Barchana, Micha; Sussman, Leon N.; Dobiner, V; Sandbank, Judith; Cagnano, Manuela; Cohen, Hector; Sabo, Edmond

doi:10.1046/j.1365-2559.2002.01444.x

Cited by 69 publications

(56 citation statements)

References 23 publications

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“…We sacrificed the mice 3 days after wounding, and checked the proliferation of dermal fibroblasts by immunofluorescence staining with the anti-Ki67 antibody, which recognizes a marker of proliferation. 17 The full-length and N-terminal domain of the p43 protein increased the number of proliferating dermal skin fibroblasts, whereas its C-terminal domain did not ( Figure 4B), consistent with the activity of p43 on fibroblasts determined in vitro (Figure 2A). Because fibroblasts are an important source of collagen during wound repair, we also examined whether collagen production is induced in fibroblasts by p43, using RT-PCR and Western blot analyses.…”

Section: Exogenous P43 Promotes Wound Repairsupporting

confidence: 80%

The Novel Cytokine p43 Stimulates Dermal Fibroblast Proliferation and Wound Repair

Park

Shin

et al. 2005

The American Journal of Pathology

100

105

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The multifunctional cytokine p43 acts on endothelial and immune cells to control angiogenesis and inflammation. In this report, we describe an additional activity of p43 that specifically promotes fibroblast proliferation and wound repair. In skin wound regions from mice, tumor necrosis factor-␣ induced p43 expression and secretion from macrophages recruited to the site. p43 also promoted fibroblast proliferation through its 146-amino acid N-terminal domain as revealed by deletion mapping. This p43-induced fibroblast proliferation was mediated by extracellular signal-regulated kinase (Erk). Depletion of endogenous p43 in mice by gene disruption retarded wound repair, whereas exogenous supplementation of recombinant human p43 to the wound area stimulated dermal fibroblast proliferation, collagen production, and wound closure. Thus, we have identified a novel p43 activity involving the stimulation of fibroblast proliferation, which could be applied therapeutically to aid wound repair. (Am J Pathol 2005, 166:387-398)

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Section: Exogenous P43 Promotes Wound Repairsupporting

confidence: 80%

The Novel Cytokine p43 Stimulates Dermal Fibroblast Proliferation and Wound Repair

Park

Shin

et al. 2005

The American Journal of Pathology

100

105

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“…This is in stark contrast with CTC in metastatic prostate and breast cancer from which a significant portion is undergoing apoptosis (29,30). The level of expression of Ki67 on melanoma cells has been associated with the aggressiveness of the disease (31)(32)(33)(34). The reported percentages of Ki67 + melanoma cells in primary and metastatic lesions in these studies are smaller as compared to the proportion of Ki67 + CMC suggesting that these CMC indeed represent very aggressive cells.…”

Section: Discussionmentioning

confidence: 99%

Circulating melanoma cells and survival in metastatic melanoma

Rao

Bui²,

Connelly³

et al. 2011

Int J Oncol

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Abstract.A validated assay for the enumeration of circulating melanoma cells (CMCs) may facilitate the development of more effective therapies for metastatic melanoma patients. In this study CD146 + cells were immunomagnetically enriched from 7.5 ml of blood. Isolated cells were fluorescently stained with DAPI, anti-molecular weight melanoma-associated antigen (HMW-MAA), anti-CD45 and CD34 and Ki67. CMCs were identified as CD146 + , HMW-MAA + , CD45 -, CD34-, Ki67 -/+ cells. Eighty-eight percent of spiked SK-MEL28 cells in 7.5 ml blood were recovered. In all 55 healthy donors ≤1 CMCs were detected in 7.5 ml of blood. A retrospective analysis was conducted comparing CMC counts and overall survival in 79 blood samples from 44 melanoma patients. CMCs ranged from 0 to 8,042 per 7.5 ml. Two or more CMCs were detected in 18 (23%) of the patients and 30-100% (mean 84%) of the CMCs expressed the proliferation marker Ki67. Patients with ≥2 CMCs per 7.5 ml of whole blood, as compared with the group with <2 CMCs, had a shorter overall survival (2.0 months vs. 12.1 months, P=0.001).

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“…In addition to the above markers, the expression of proliferating cell nuclear antigen (PCNA) was determined. PCNA had previously been correlated with aggressive behavior in human cutaneous malignant melanomas (Ben-Izhak et al 2002).…”

Section: Introductionmentioning

confidence: 99%

Isolation, establishment, and characterization of ex vivo equine melanoma cell cultures

Chapman

Metzger

Grest

et al. 2008

In Vitro Cell.Dev.Biol.-Animal

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Gray horses spontaneously develop metastatic melanomas that resemble human disease, and this is often accompanied with metastasis to other organs. Unlike in other species, the establishment of primary equine melanoma cultures that could be used to develop new therapeutic approaches has remained a major challenge. The purpose of the study was to develop a protocol for routine isolation and cultivation of primary equine melanocytes. Melanoma tissues were excised from 13 horses under local anesthesia, mainly from the perianal area. The melanoma cells were isolated from the melanoma tissue by serial enzymatic digestion using dispase and collagenase. Out of the 13 excised melanomas, cell cultures from eight melanomas were established, which corresponded to a success rate 62%. These cells showed different degrees of melanin pigmentation. Characterization of these cells using confocal microscopy, FACs analysis and western blotting showed that they expressed melanoma-associated antigens; Melan-A, MAGE-1, and MAGE-3, and PCNA expression was higher in fast-proliferating isolates. The protocol we developed and established proved successful for routine isolation and cultivation of primary equine melanoma cells. This method provided a large number of primary equine melanoma cells that could be used to study new therapeutic approaches for treatment of equine melanomas.

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Ki67 antigen and PCNA proliferation markers predict survival in anorectal malignant melanoma

Abstract: Ki67 and PCNA immunostaining in paraffin sections may be useful for the prediction of survival in patients with anorectal malignant melanoma. Larger studies are needed to confirm our results.

Cited by 69 publications

References 23 publications

The Novel Cytokine p43 Stimulates Dermal Fibroblast Proliferation and Wound Repair

The Novel Cytokine p43 Stimulates Dermal Fibroblast Proliferation and Wound Repair

Circulating melanoma cells and survival in metastatic melanoma

Isolation, establishment, and characterization of ex vivo equine melanoma cell cultures

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