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Query: UMLS:C0025202 (melanoma)
 69,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tumor-infiltrating lymphocytes (TIL) from a wide range of human and murine tumors can be expanded in vitro using interleukin-2 (IL-2). These TIL are cytolytic T lymphocytes with in vivo and in vitro antitumor activity in mice and in humans. TIL from human melanoma can recognize autologous tumor in an MHC-restricted fashion, localize in vivo after 111In labeling, and mediate regression of large metastatic deposits. Although studied extensively in vitro, less is known in vivo about TIL activity associated with tumor regression. This study was undertaken, in association with a study of TIL localization, to investigate mechanisms of TIL action by evaluating histopathological changes that occur at the tumor site during TIL administration. A total of 106 pre- and post-treatment pathological specimens from 25 patients enrolled in phase II TIL treatment and 111In-TIL imaging protocols were examined blindly by a single pathologist. Histological subtype, lymphocytic infiltration, melanin content, vascularity, and necrosis were documented for each tumor specimen. Average baseline and post-treatment parameters were compared. Any significant changes were evaluated for correlation with clinical response and 111In-TIL localization to tumor. Melanin content and vascularity of the tumor did not change as a result of therapy or correlate with either response or TIL localization. However, both increased lymphocytic infiltration and tumor necrosis were present after TIL administration (P = 0.044 and 0.032 respectively). Furthermore, increases in lymphocytic infiltration correlated with tumor imaging using 111In-TIL, and with the percentage of 111In-labeled injectate present per gram of tumor specimen (P = 0.036 and 0.0041 respectively). This suggests that TIL either account for the increased lymphocytes directly, or localize to tumor and recruit endogenous lymphocytes. We were unable to demonstrate any pretreatment histopathological predictors of response or variables that significantly correlated with subsequent clinical response, although peak and average values of necrosis were higher in responding patients compared to non-responding patients.
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PMID:Histopathological analysis of metastatic melanoma deposits in patients receiving adoptive immunotherapy with tumor-infiltrating lymphocytes. 816 11

Sixteen cases of malignant melanoma which showed prominent desmoplastic and/or neurotropic features occurring throughout the tumour were compiled from the St John's Dermatology Centre histopathological archives. A further nine melanomas in which both conventional and desmoplastic melanoma were present concomitantly were also studied (three tumours with 66% desmoplastic change, two with 50%, and four with less than 50%). There were 14 males and 11 females, with a mean age of 64 years (range 39-86). The mean interval between presentation and diagnosis was 8 months. Eighteen of the 25 tumours were located on the head and neck, three were on the trunk, one was on the upper limb and three were on the lower limb. Histological review revealed 21 of 25 tumours with overlying atypical lentiginous hyperplasia, lentigo maligna melanoma, or superficial spreading malignant melanoma. Neurotropism was present in nine tumours, with the changes confined to local recurrences in two instances; neuroid differentiation was present in four tumours, and neural and perineural tumour spread was present in four tumours. The depth of invasion exceeded 6 mm in seven tumours, and was 2-6 mm in 16, and less than 2 mm in two. Eighteen of the 25 tumours were incompletely excised at the time of the first excision. Lymphoid aggregates were present in 16 tumours, but in most cases were limited to a few lymphoid foci. Melanin was identified in the dermal component of only five tumours, but not in areas showing typical histological features of desmoplastic malignant melanoma. Treatment was by surgical excision in all cases, and was preceded by radiotherapy in one case. Details of follow-up were obtained in all cases, and the duration ranged from 9 months to 10 years (mean, 3 years 11 months). Eleven patients had died; nine from melanoma and two from other causes. One patient was alive, with deep, inoperable local recurrence. Thirteen patients were alive and clinically free from tumour, including two patients in whom there had been local recurrence. A lower rate of neurotropism was present in the nine patients with partial desmoplastic change compared with those with desmoplasic change throughout the tumour, and represented the only significant difference between the two groups of patients.
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PMID:Desmoplastic malignant melanoma: a clinicopathological study of 25 cases. 821 47

The fine needle aspiration findings in a lymph node involved by signet-ring cell melanoma, a very rare variant of malignant melanoma, are reported. The patient had a history of superficial spreading melanoma of the right foot, treated 10 years earlier by below-the-knee amputation. He presented with a right groin mass. Fine needle aspiration of the mass yielded poorly cohesive, large cells with eccentric nuclei and abundant, eosinophilic cytoplasm; many of them exhibited a signet-ring appearance. Melanin pigments were identified in a small proportion of tumor cells, and a diagnosis of metastatic melanoma was made. The subsequent lymph node excision revealed a metastatic tumor composed of polygonal and signet-ring cells that were positive for S-100 protein and HMB-45 but not cytokeratin. Nearly all reported cases of signet-ring cell melanoma occurred as metastatic or recurrent disease. It is important not to mistake signet-ring cell melanoma for adenocarcinoma in aspiration cytology, and a constellation of clinical features and of histochemical and immunohistochemical findings enables a correct diagnosis to be reached.
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PMID:Signet-ring cell melanoma mimicking adenocarcinoma. A case report. 832 53

Monolayer cultures of Harding-Passey melanoma cells in exponential growth phase were exposed to 8 or 16 Gy by X-ray treatment. The 8 Gy treated cells revealed little ultrastructural changes, while the 16 Gy exposed cells showed increased damage as segregates, swollen mitochondria and vacuoles. Sole treatment with L-3,4-dihydroxyphenylalanine (2 x 10(-4) M L-Dopa) resulted in insignificant electronmicroscopically tangible cell alterations. Combined treatment--starting with 8 Gy irradiation followed by a six-day incubation in the presence of 2 x 10(-4) M L-Dopa--revealed more pronounced cell damage with final cell disintegration; the cytoplasm contained an increased number of vacuoles and segregates, a strongly decreased endoplasmic reticulum as well as swollen mitochondria and less pinocytosis vesicles; the cell surface showed less microvilli. Melanin containing organelles increased after the combination treatment. The growth inhibitory and cell destructive influence of L-Dopa on X-ray pretreated melanogenic melanoma cells was explained with the formation of cytotoxic oxidation products of L-Dopa.
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PMID:[Electron microscopic studies of the effect of x-rays and L-3,4-dihydroxyphenylalanine (L-Dopa)--alone and in combination-- on Harding-Passey melanoma cells in monolayer cell culture]. 835 10

A sulfur-containing amino acid compound, S-allyl cysteine (SAC), derived from garlic extract inhibited proliferation of nine human and murine melanoma cell line in a dose-dependent manner (1.2-10 mM) assessed by a [3H]thymidine incorporation assay. Three control human lymphoblastoid cell lines were not inhibited by SAC concentrations < 5 mM. Four human melanoma cell lines in a soft-agar assay also showed dose-dependent inhibition of colony formation by SAC. Melanin content was increased up to 95% compared to the same untreated cell lines in these four human melanoma and two B16 murine melanoma sublines. Expression of cell surface gangliosides, cellular-differentiation and transformation markers, decreased after SAC treatment. Significant morphological changes including 'flattening and/or dendritic-like elongations' were also observed. Thus SAC inhibited cellular growth and proliferation and modulated major cell differentiation markers of melanoma.
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PMID:Growth inhibition and modulation of cell markers of melanoma by S-allyl cysteine. 842

Using antibodies that recognize either tyrosinase, tyrosinase-related protein-1 (TRP1), or tyrosinase-related protein-2 (TRP2, DOPAchrome tautomerase), the quantities of those melanogenic enzymes were analyzed in five melanoma cell lines that possess various degrees of melanin production. All cells except JB/MS-W increased melanin production four to 30 times after 4 d of melanocyte-stimulating hormone (MSH) treatment. Melanin production by JB/MS-W cells was always under background, with or without MSH treatment. There was a positive correlation between quantities and synthetic rates of those melanogenic enzymes and their melanin formation or DOPAchrome tautomerase activities. The activity of a heat-resistant melanogenic inhibitory factor was also analyzed. The results showed, surprisingly, that pigmented cells showed higher levels of melanogenic inhibitors activity. Tyrosinase activity was increased dramatically whereas the level of melanogenic inhibitor was remarkably decreased following MSH treatment. Interestingly, melanogenic inhibitor derived from JB/MS-W cells suppressed not only tyrosinase but also DOPAchrome tautomerase, another enzyme functional in melanin production. These results clearly suggest that melanin production is regulated by a subtle balance between the activities of these enzymes and other factors such as the melanogenic inhibitor.
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PMID:Pigment production in murine melanoma cells is regulated by tyrosinase, tyrosinase-related protein 1 (TRP1), DOPAchrome tautomerase (TRP2), and a melanogenic inhibitor. 842 35

Tyrosinase activity is a key determinant of melanin production in skin. Because retinoic acid regulates tyrosinase activity in melanoma cells, we analyzed modulation of pigmentation in vivo by retinoic acid. Black and white subjects were either not treated, or treated topically for 4 d under occlusion with vehicle, retinoic acid (0.1%), or the irritant sodium lauryl sulfate (2%). In untreated skin, tyrosinase activity and melanin content were significantly greater (2.3 times, and 3.2 times, respectively) in blacks versus whites. Four days of treatment with topical retinoic acid did not alter tyrosinase activity or melanin content in black skin. In contrast, retinoic acid treatment significantly induced (2.7 times, n = 8) tyrosinase activity, compared to vehicle treatment, in white skin. Melanin content, however, remained unchanged at 4 d. In separate experiments, tyrosinase activity in white subjects (n = 25) was increased 16% (p = 0.01) in sodium lauryl sulfate-treated skin, and 77% (p = 0.0005) in retinoic acid-treated skin, compared to vehicle-treated skin. The effect of retinoic acid on tyrosinase activity could be differentiated from non-specific irritation, because tyrosinase activity in retinoic acid-treated skin was significantly greater (52%, p = 0.004) than sodium lauryl sulfate-treated skin. Similar results were obtained with the dihydroxyphenylalanine reaction done on vehicle, sodium lauryl sulfate-, and retinoic acid-treated white skin. Northern analysis (n = 6) and semi-quantitative polymerase chain reaction (n = 6) demonstrated that retinoic acid treatment did not alter tyrosinase mRNA levels in white skin. Western analysis revealed that induction of tyrosinase activity by retinoic acid also was not associated with increased tyrosinase protein content (n = 9), indicating that regulation of tyrosinase activity by retinoic acid occurs through a post-translational mechanism. These data demonstrate that low tyrosinase activity in white skin in vivo is retinoic acid inducible and high tyrosinase activity in black skin in vivo is neither further induced nor reduced by retinoic acid.
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PMID:Differential regulation of tyrosinase activity in skin of white and black individuals in vivo by topical retinoic acid. 849 19

A cell line was established from a Mongolian gerbil's (Meriones unguiculatus) homotransplantable malignant melanoma. Ascitic tumor cells detected in a gerbil when transplanted intraperitoneally were adapted to culture. In primary culture, cells were divided into 2 types, multipolar and polygonal cells. Cell masses which adhered to polygonal cells were observed after the 6th passage. The adhering cells were removed and transferred into another flasks. The cells showed multipolar and possessed projections. Then after, the cells increased in number vigorously and formed acinous structures. At early passages, abundant melanin granules in some of the cells were demonstrated by light and electron microscopical observations. Most of the cells were positive by DOPA reaction. Melanin pigments were gradually decreased through the 20th to 30th passage and most of cells became amelanotic. The doubling time of the cell line was 32 hr. Chromosome number of the cell line ranged from 68 to 82. Whitish tumors were produced in the abdominal cavity within 30 days when intraperitoneally inoculated the cells to gerbils. This cell line, designated as MGM-A, has been subcultured for more than 100 passages during 2 years.
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PMID:Characterization of cultured cells derived from Mongolian gerbil's (Meriones unguiculatus) ascitic malignant melanoma. 851 2

Sodium 5,6-benzylidene ascorbate (SBA) is a conjugate of ascorbic acid (Asc) with benzyaldehyde. It has been found that the antioxidant activity of SBA is more stable and has a longer lifetime in living cells and organs than Asc. In this study, we investigated the effect of SBA on the induction of melanin in cultured melanoma (B-16) cells irradiated by UV-A. Melanin content of B-16 cells was significantly increased by UV-A irradiation. The induction was abolished by mannitol and particularly by superoxide dismutase, suggesting the involvement of O2- in the biosynthesis of melanin in cultured melanoma cells. This was theorized by the fact that the induction was also observed in B-16 cells treated with superoxide anion radicals chemically generated in the hypoxanthine/xanthine oxidase-reaction system, instead of UV-A irradiation. The induction of melanin caused by UV-A irradiation was suppressed by SBA in a dose-dependent manner. To elucidate the mechanism of this suppressive effect, the scavenging activity against O2-, and the inhibitory effect of SBA on tyrosinase activity were examined. ESR spectrometric analysis showed that SBA strongly scavenged O2-, and the presence of SBA in the medium remarkably inhibited the tyrosinase activity in cultured B-16 melanoma cells. It can be concluded that SBA effectively inhibits the melanin biosynthesis in B-16 melanoma cells induced by reactive oxygen species (ROS) generated by UV-A irradiation via tyrosinase.
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PMID:Inhibitory effect of sodium 5,6-benzylidene ascorbate (SBA) on the elevation of melanin biosynthesis induced by ultraviolet-A (UV-A) light in cultured B-16 melanoma cells. 853 99

4 clonal sublines of Cloudman S91 melanoma cells, S91/mel, S91/I3, S91/6 and S91/amel, were evaluated for changes in growth, pigment content and plating efficiency during and after treatment with a cyclic-AMP phosphodiesterase inhibitor-melanin-stimulating agent, 3-isobutyl-1-methyl-xanthine (IBMX) plus beta-melanocyte stimulating hormone (beta-MSH) or IBMX alone. After combined treatment, increases in melanin content on day 3 were 48, 27, 11, and 2 pg/cell in the four cell lines respectively. In each case IBMX alone was less effective than IBMX plus beta-MSH. Doubling time increased and plating efficiency decreased with increased melanization. The increases in doubling time and decreases in plating efficiency were cell line dependent. The greatest rate of increase in doubling time and decrease in plating efficiency as a function of melanin content were seen in S91/amel, which produced the least pigment. The lowest rates of increase/decrease were seen in S91/mel, which produced the most pigment. Melanin pigment induced in the cells was classified as eumelanin by EPR determination. The differential response to induction of pigmentation makes these cell lines suitable models for comparative studies on the role of melanin in pigment cell biology.
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PMID:Growth and pigmentation in genetically related Cloudman S91 melanoma cell lines treated with 3-isobutyl-1-methyl-xanthine and beta-melanocyte-stimulating hormone. 853 13


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