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Biomedical subjects

James M Grichnik

Publications and source records attributed to James M Grichnik.

At least 19 recordsLinked to original sources
PubMed2006

Melanoma, a tumor based on a mutant stem cell?

Stem cells play a critical role in normal tissue maintenance, and mutations in these stem cells may give rise to cancer. We hypothesize that melanoma develops from a mutated stem cell and therefore residual stem cell characteristics should be able to be identified in melanoma cell lines. We studied three metastatic melanoma cell lines that exhibited multiple morphologic forms in culture and demonstrated the capacity to pigment. We used the ability to efflux Hoechst 33342 dye, a technique known to enrich for stem cells in many tissues, to segregate cell populations. The cells with the greatest ability to efflux the dye were (1) small in size, (2) had the capacity to give rise to larger cell forms, and (3) had the greatest ability to expand in culture. The small cells were found to have a decreased proliferative rate and were less melanized. Large dendritic cells that appeared to be nonproliferative were identified in cultures. Treatment with cytosine beta-D-arabinofuranoside hydrochloride (Ara-C) expanded the large cell population but the residual proliferative capacity, both in vitro and in vivo, remained concentrated in the smaller cell fraction. Antigenic staining patterns were variable and heterogeneous. Nestin (a neural stem cell marker) and gp100 (premelanosomal marker) favored the smaller cell population, while nerve growth factor receptor often labeled larger cells. Morphologic and antigenic heterogeneity remained intact after clonal purification. These findings are consistent with the behavior expected for a tumor based on stem cell biology; this finding has diagnostic and therapeutic implications for melanocytic neoplasias.

Antigens, Neoplasm↗
PubMed2006

Kit and melanocyte migration.

As described in this issue, Alexeev and Yoon introduced a Kit-activating mutation into melanocytes. Although mitogenic in mast cells, this mutation was motogenic in melanocytes. Further, melanocytes had a reduced proliferative rate and were less differentiated. The disparate response may be due to differences in the cellular milieu of melanocytes and may have implications for normal melanocytic integration into the epidermis, nevogenesis, and melanoma.

Animals↗
PubMed2006

Genomic instability and tumor stem cells.

Wang et al. point to the existance of a common progenitor tumor stem cell that gives rise to genomically unstable progeny in malignant melanoma. Although it is not known what creates this genomic instability, given the presence of testis antigens in melanoma, it is tempting to speculate that it is caused by a collision of meiotic and mitotic pathways.

Genomic Instability↗
PubMed2005

Ferulic acid stabilizes a solution of vitamins C and E and doubles its photoprotection of skin.

Ferulic acid is a potent ubiquitous plant antioxidant. Its incorporation into a topical solution of 15%l-ascorbic acid and 1%alpha-tocopherol improved chemical stability of the vitamins (C+E) and doubled photoprotection to solar-simulated irradiation of skin from 4-fold to approximately 8-fold as measured by both erythema and sunburn cell formation. Inhibition of apoptosis was associated with reduced induction of caspase-3 and caspase-7. This antioxidant formulation efficiently reduced thymine dimer formation. This combination of pure natural low molecular weight antioxidants provides meaningful synergistic protection against oxidative stress in skin and should be useful for protection against photoaging and skin cancer.

Animals↗
PubMed2003

Dermoscopy of pigmented skin lesions: results of a consensus meeting via the Internet.

BACKGROUND: There is a need for better standardization of the dermoscopic terminology in assessing pigmented skin lesions. OBJECTIVE: The virtual Consensus Net Meeting on Dermoscopy was organized to investigate reproducibility and validity of the various features and diagnostic algorithms. METHODS: Dermoscopic images of 108 lesions were evaluated via the Internet by 40 experienced dermoscopists using a 2-step diagnostic procedure. The first-step algorithm distinguished melanocytic versus nonmelanocytic lesions. The second step in the diagnostic procedure used 4 algorithms (pattern analysis, ABCD rule, Menzies method, and 7-point checklist) to distinguish melanoma versus benign melanocytic lesions. kappa Values, log odds ratios, sensitivity, specificity, and positive likelihood ratios were estimated for all diagnostic algorithms and dermoscopic features. RESULTS: Interobserver agreement was fair to good for all diagnostic methods, but it was poor for the majority of dermoscopic criteria. Intraobserver agreement was good to excellent for all algorithms and features considered. Pattern analysis allowed the best diagnostic performance (positive likelihood ratio: 5.1), whereas alternative algorithms revealed comparable sensitivity but less specificity. Interobserver agreement on management decisions made by dermoscopy was fairly good (mean kappa value: 0.53). CONCLUSION: The virtual Consensus Net Meeting on Dermoscopy represents a valid tool for better standardization of the dermoscopic terminology and, moreover, opens up a new territory for diagnosing and managing pigmented skin lesions.

Algorithms↗
PubMed2003

Early melanoma detection: nonuniform dermoscopic features and growth.

BACKGROUND: Dermoscopy alone is not sufficient to detect all early melanomas. Total body photos reveal growth of melanomas but also reveal growth of melanocytic nevi. OBJECTIVE: We set out to determine whether a simplified algorithm on the basis of nonuniform dermoscopic features combined with growth noted from baseline total body photos targeted the early melanocytic neoplasms most likely to be malignant. METHODS: Lesions removed during follow-up of patients with total body photographs were reviewed and 169 melanocytic lesions were identified for which both gross clinical and dermoscopic photos were available. The images were evaluated separately by 3 academic dermatologists, without knowledge of the given pathologic diagnosis, for uniformity (consistent gradient of features from center to edge) and change (specifically, that which could indicate melanoma growth in normal skin or within a nevus). RESULTS: Using a minimum of 2 out of 3 agreement for uniformity and change, 12 of 16 melanomas (including all 5 superficially invasive tumors) were graded as nonuniform and changed. The 4 melanomas not included in this category were in situ. The predicted odds of melanoma for lesions scored as both nonuniform and changed was 4.06 (P >.0195). If 3 out of 3 agreement was used, the odds ratio increased to 6 (P >.0010). CONCLUSION: An algorithm on the basis of dermoscopic nonuniformity and change suggestive of growth as determined by total body photography segregates melanocytic neoplasms most likely to be malignant.

Algorithms↗
PubMed2003

UV photoprotection by combination topical antioxidants vitamin C and vitamin E.

BACKGROUND: Virtually all plants and animals protect themselves from the sun using vitamins C and E. OBJECTIVE: The purpose of this study was to see if a combination of topical vitamins C and E is better for UV protection to skin than an equivalent concentration of topical vitamin C or E alone. METHODS: We developed a stable aqueous solution of 15% L-ascorbic acid (vitamin C) and 1% alpha-tocopherol (vitamin E). We applied antioxidant or vehicle solutions to pig skin daily for 4 days. We irradiated (1-5x minimal erythema dose) control- and antioxidant-treated skin using a solar simulator with a 295-nm band-pass filter. On day 5, we measured antioxidant protection factor, erythema, sunburn cells, and thymine dimers. RESULTS: The combination of 15% L-ascorbic acid and 1% alpha-tocopherol provided significant protection against erythema and sunburn cell formation; either L-ascorbic acid or 1% alpha-tocopherol alone also was protective but the combination was superior. Application during 4 days provided progressive protection that yielded an antioxidant protection factor of 4-fold. In addition, the combination of vitamins C and E provided protection against thymine dimer formation. CONCLUSION: Appreciable photoprotection can be obtained from the combination of topical vitamins C and E. We suggest that these natural products may protect against skin cancer and photoaging.

Animals↗