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A Slominski

Publications and source records attributed to A Slominski.

At least 37 records · Page 2Linked to original sources
PubMed2000

Experimental ruthenium plaque therapy of amelanotic and melanotic melanomas in the hamster eye.

The effects of beta-radiation on melanoma implanted into the hamster's eye were investigated. Two Bomirski hamster melanomas (BHMs), differing in their melanin content, were compared with regard to their radiosensitivity to ruthenium-106 (106Ru) radiation. Tumours growing in the iris were irradiated with 3, 6 or 10 Gy of 106Ru given as a single dose or in four fractions at 24 h Intervals. Tumour growth kinetics and distant metastases were studied, and the eyeballs were examined histologically. Dose-dependent delay of tumour growth was observed in both melanomas. After treatment with a dose of 6 Gy, the Ab amelanotic tumours grew 2.6 times slower, and the Ma melanotic tumours 1.4 times slower than untreated ones. The location of metastases differed in the two tested lines--pigmented metastases were found mainly in the lungs, while unpigmented metastases were found mainly in the kidneys. Histopathological analysis showed signs of blood vessel damage such as endothelial cells swelling, erythrocyte extravasation and tumour necrosis. This last finding increased with the rising dose of beta-radiation. Pigmented tumours were found to be two times more resistant to beta-radiation than amelanotic ones. The pattern of metastases of BHMs is determined by the type of melanoma (Ab or Ma). Exposure to beta-radiation from 106Ru did not significantly affect either the number or size of metastases except at a dose of 10 Gy. This dose caused a statistically significant decrease in the number of metastases in the Ma melanotic subline.

Animals↗
PubMed1999

UV light and MSH receptors.

Ultraviolet B (UVB) radiation in the skin induces pigmentation that protects cells from further UVB damage and reduces photocarcinogenesis. Although the mechanisms are not well understood, our laboratory has shown that UVB radiation causes increased MSH receptor activity by redistributing MSH receptors from internal pools to the external surface, with a resultant increase in cellular responsiveness to MSH. By this means, UVB and MSH act synergistically to increase melanin content in the skin of mice and guinea pigs. In humans, MSH causes increased skin pigmentation, predominantly in sun-exposed areas. We have shown recently that UVB irradiation and exposure to MSH or to dbcAMP, stimulates production of mRNAs for both alpha MSH receptors and POMC in human melanocytes and keratinocytes. This indicates that at least one action of UVB on the pigmentary system is mediated through increased MSH receptor production, as well as through the production of the signal peptides, MSH and ACTH, that can further activate MSH receptors. The results add support to the hypothesis that the effects of UVB on cutaneous melanogenesis are mediated through a series of coordinated events in which MSH receptors and POMC-derived peptides play a central role.

Animals↗
PubMed1999

The skin POMC system (SPS). Leads and lessons from the hair follicle.

Human and murine skin are prominent extrapituitary sources and targets for POMC products. The expression of, for example, ACTH, alpha-MSH, beta-endorphin, and MC-1-receptors fluctuates during synchronized hair follicle cycling in C57BL/6 mice. Since hair growth can be induced by ACTH injections in mice and mink, and since high doses of MSH peptides modulate epidermal and/or follicle keratinocyte proliferation in murine skin organ culture, some POMC products may operate as locally generated growth modulators, in addition to their roles in cutaneous pigment and immunobiology. Intrafollicularly generated ACTH and alpha-MSH as well as their cognate receptors may assist in the maintenance of the peculiar immune privilege of the anagen hair bulb. Possibly, they are also involved in the development of the follicle pigmentary unit, with whose generation their expression coincides. Given that murine skin also expresses (in a hair-cycle-dependent way) CRH and CRH-R, which control pituitary POMC expression and in view of the fact that CRH arrests follicles in telogen, this suggests the existence of a local skin POMC system (SPS). This may be an integral component of cutaneous stress response-systems, and may most instructively be studied using the murine hair cycle as a model.

Adrenocorticotropic Hormone↗
PubMed1999

Metabolism of progesterone to DOC, corticosterone and 18OHDOC in cultured human melanoma cells.

We are now showing that cultured human melanoma cells can synthesize steroids such as corticosterone from progesterone or deoxycorticosterone. Corticosterone production is strongly responsive to deoxycorticosterone substrate addition (12-fold increase), but unresponsive to the adrenal stimulating factors ACTH and angiotensin II. This is the first demonstration that skin cells (malignant melanocytes) have the capability to synthesize 11-deoxycorticosterone, corticosterone, and 18-hydroxydeoxycorticosterone.

Adrenal Glands↗
PubMed1999

Expression of proopiomelanocortin (POMC)-derived melanocyte-stimulating hormone (MSH) and adrenocorticotropic hormone (ACTH) peptides in skin of basal cell carcinoma patients.

We proposed that local expression and production of proopiomelanocortin (POMC) peptides may play a role in human skin physiology and pathology, including the development and progression of skin cancers. Reverse transcription polymerase chain reaction (RT-PCR) and Northern blotting hybridization techniques were used to study gene expression. Reversed-phase (RP) high-pressure liquid chromatography (HPLC) separation with subsequent radioimmunoassays were used to identify alpha-melanocyte-stimulating hormone (alpha-MSH) and adrenocorticotropic hormone (ACTH) peptides. Immunocytochemistry (IHC) was used to localize ACTH, alpha-MSH, and beta-MSH antigens in skin. RT-PCR, RP-HPLC, and IHC analyses documented the expression of POMC mRNA and production of ACTH and alpha-MSH peptides in lesional and perilesional skin of basal cell carcinoma (BCC) patients and in cultured keratinocytes, which was accompanied by the expression of the MC1-R gene encoding the receptor activated by MSH and ACTH. Thirty specimens were analyzed by IHC. Immunoreactive alpha-MSH, beta-MSH, and ACTH were detected, in 21 of 21, in 11 of 20, and in 6 of 8 of lesional skin, and in 6 of 6, in 5 of 7, and in 6 of 8 perilesional skin specimens analyzed, respectively. Antigen distribution was heterogenous and present in BCC, epidermis, hair follicles, dermal mononuclear cells, and extracellular matrix. We conclude that messenger RNA for POMC, MC1-R, and the peptides MSH and ACTH are produced in skin of BCC patients. Because keratinocytes are a target for MSH and ACTH bioregulation, the production of these peptides is stimulated by UVB, and the peptides can act as immunosupressors, we suggest that MSH and ACTH may facilitate development of BCC.

Adrenocorticotropic Hormone↗
PubMed1999

The fate of hair follicle melanocytes during the hair growth cycle.

The fate of the follicular pigmentary unit during the hair growth cycle has long been one of the great enigmas of both hair follicle and pigment cell biology. Although melanocytes are distributed in several different compartments of the anagen hair follicle, melanogenically active cells are located only in the hair bulb, where they are directly involved in hair shaft pigmentation. These pigment cells are readily detectable only when they become melanogenically active during anagen III of the hair growth cycle. Thus, their status during hair follicle regression (catagen), when melanogenesis is switched off, until they re-appear again as pigment-producing cells in the anagen III hair follicle, has remained poorly defined. Historically, it has been proposed that hair bulb melanocytes adopt a self-perpetuating, catagen-resistant strategy of de-differentiation during hair follicle regression and re-differentiation upon entry into a new anagen phase; however, this explanation remains problematic in the absence of evidence for de-differentiation/re-differentiation plasticity in most nonmalignant cell systems.

Animals↗
PubMed1999

Down-regulation of the expression of O-acetyl-GD3 by the O-acetylesterase cDNA in hamster melanoma cells: effects on cellular proliferation, differentiation, and melanogenesis.

The composition of the gangliosides of hamster melanoma cells is closely related to their cellular growth and degree of differentiation, with slow-growing, highly differentiated melanotic melanoma MI cells expressing GM3 and fast-growing, undifferentiated amelanotic Ab melanoma cells having a preponderance of GD3 and O-acetyl-GD3. To study the putative function of O-acetyl-GD3, we established stably transfected AbC-1 amelanotic hamster melanoma cells with O-acetylesterase gene from influenza C virus to hydrolyze the O-acetyl group from O-acetyl-GD3. The content of O-acetyl-GD3 in the transfected cells expressing O-acetylesterase gene was reduced by >90%. These O-acetyl-GD3-depleted cells differed from the parental ones in their cellular morphology, growth behavior, and melanogenesis activity. The absence of O-acetyl-GD3 in the transfected cells was accompanied by increased thick dendrite formation with an enlarged cell body, which is in striking contrast to the control cells, which were rounded and flattened, with few processes. Their growth was significantly slower than that of the control cells. They also demonstrated significantly lower tyrosinase activity and melanogenic potential. We suggest that the enhanced expression of melanoma-associated O-acetyl-GD3 ganglioside may stimulate cellular growth and suppress certain differentiated phenotypes such as dendrite formation but not melanogenesis.

Acetylesterase↗
PubMed1999

Melanocytic matricoma: a report of two cases of a new entity.

Many reports exist of pigmented adnexal tumors containing dendritic melanocytes such as pigmented basal cell carcinomas and pigmented pilomatricomas. Correspondingly, melanocytes are a known component of the bulbs of anagen follicles. The phenomenon of melanization of adnexal tumors highlights the interrelationship between melanocytes and adnexal epithelium and may represent normal melanocytes colonizing a neoplastic proliferation. We report on two cases of a unique tumor composed of neoplastic matrical cells with a significant component of melanocytes. Both cases presented as pigmented papules in older men (66 and 80 years, forearm and pectoral region, respectively). Histologically, these were well-defined nodular proliferations composed of variably melanized, pleomorphic, and mitotically active matrical and supramatrical cells forming clusters of "shadow cells." Admixed with the epithelial cells were numerous melanized dendritic melanocytes. Shadow cells expressed keratin 13, and a subpopulation of S-100 protein-positive dendritic cells were evident. No recurrence of any type was found after reexcisions 4 months and 2 years later. We propose the name of melanocytic matricoma for these two heretofore unreported cases of a unique neoplasm composed of matrical cells and melanocytes recapitulating epithelial-melanocyte interaction in the follicular anagen bulb. Although their small size, circumscription and clinical course suggest a benign nature, melanocytic matricomas' cytologic atypia disclose the potential for malignant behavior.

Aged↗
PubMed1999

Molecular pathology of soft tissue and bone tumors. A review.

OBJECTIVE: To present recent concepts on the molecular pathogenesis of tumors of soft tissue and bone, and on the use of molecular genetic methods, including their significance as diagnostic markers and prognostic indicators. DATA SOURCES AND STUDY SELECTION: Reports on tumors of bone and/or soft tissue published in the English language literature and observations made using specimens available at the Departments of Pathology at Albany Medical College and Loyola University Medical Center. DATA EXTRACTION AND SYNTHESIS: Studies on bone and soft tissue tumors containing chromosomal or genetic evaluation were selected for further analysis. Specific chromosomal abnormalities, such as numerical aberrations or translocations with production of fusion genes, were classified according to the tumor of origin. Data were also collected on mutations in tumor suppressor genes, genes coding for growth factors or their receptors, and genes coding for tyrosine kinases. Also noted were mutations of uncertain significance, for which the pathogenic connection between tumor production and mutated gene function is still unclear. CONCLUSIONS: In general, the mutations reported interfere with the action of peptide growth factors coordinating mesenchyme proliferation and differentiation, although membrane-bound receptors expressing the intracellular signaling modifier, tyrosine kinase activity, have also been involved. Functional types of genes most commonly affected include tumor suppressors, oncogenes, and nuclear transcription factors. Thus, the mutations involved in the pathogenesis of soft tissue and bone tumors have affected multiple genes. Moreover, aberrant fusion gene products may be formed in tumoral tissue and may then act as transcription regulators stimulating cellular proliferation. Cytogenetic studies help at the clinical level by demonstrating aneuploidy and increased ploidy, which may correlate with malignant behavior. Diagnostic tumor-specific chromosomal translocations may be detected with Southern hybridization analysis, polymerase chain reaction, reverse-transcription polymerase chain reaction, or with the fluorescence in situ hybridization technique. Notably, early metastatic disease may be detectable in blood specimens using polymerase chain reaction or reverse-transcription polymerase chain reaction techniques.

Bone Neoplasms↗
PubMed1998

Hair cycle-dependent production of ACTH in mouse skin.

We investigated the functional determinants of the cutaneous expression of elements of the hypothalamic-pituitary-adrenal axis. In the present work, the presence of adrenocorticotropin (ACTH) peptide in skin of C57/BL6 mouse was demonstrated by reversed-phase HPLC analysis combined with specific radioimmunoassay. ACTH concentration that was low in telogen, increased during anagen in two steps: a rapid phase in anagen I, and a slower rise that reached its peak in anagen VI. Immunofluorescence localized the ACTH antigen to the basal layer of epidermis, outer root sheath of hair follicle and subcutaneous muscle of anagen VI skin. At physiological plasma concentration (10-9 M), ACTH selectively stimulated DNA synthesis in dermis, while pharmacological doses (10-7-10-6 M) inhibited DNA synthesis in both dermis and epidermis. In conclusion, we suggest that local production of ACTH may represent a regulatory element in the control of skin functions including hair growth.

Adrenocorticotropic Hormone↗
PubMed1998

Effect of CRF and related peptides on calcium signaling in human and rodent melanoma cells.

Corticotropin releasing factor (CRF) induces a rapid, within seconds, and dose-dependent increase in the intracellular Ca2+ in both human and hamster melanoma cells. This effect is inhibited by depletion of extracellular calcium using 3 mM EGTA and is attenuated by the CRF receptor antagonist, alpha-helical-CRF(9-41). Other peptides of the CRF superfamily, sauvagine and urocortin, also induce increases in cytoplasmic calcium concentration but at higher concentrations than CRF. We conclude that malignant melanocytes express CRF receptors, which are coupled to activation of plasma membrane calcium channels.

Amphibian Proteins↗
PubMed1998

Cutaneous immunomodulation and coordination of skin stress responses by alpha-melanocyte-stimulating hormone.

The capacity of the skin immune system to mount various types of immune responses is largely dependent on their ability to release and respond to different signals provided by immunoregulatory mediators such as cytokines. There is recent evidence that neuropeptides such as alpha-melanocyte-stimulating hormone (alpha MSH), upon stimulation, are released by epidermal cells including keratinocytes, Langerhans cells, and melanocytes as well as immunocompetent cells. Moreover, alpha MSH recently has been recognized as a potent immunomodulating agent, which inhibits the production and activity of immunoregulatory and proinflammatory cytokines such as IL-1, IL-2, interferon-gamma, downregulates the expression of costimulatory molecules (B7) on antigen-presenting cells; and recently turned out to be a potent inducer of inhibitory mediators such as cytokine synthesis inhibitory factor interleukin-10. Recently, it also was discovered that monocytes among the five known melanocortin (MC) receptors only express MC-1, which is specific for alpha MSH. The expression of MC-1 on monocytes is upregulated by mitogens, endotoxins, and proinflammatory cytokines. There is also recent evidence for the in vivo relevance of the immunosuppressing capacity of alpha MSH. Accordingly, in animals alpha MSH has been shown to inhibit the induction of contact hypersensitivity reactions and to induce hapten-specific tolerance. These findings indicate that, in addition to the cytokine network, neurohormones within the cutaneous microenvironment are a crucial element for the induction, elicitation, and regulation of cutaneous immune and inflammatory responses.

Animals↗