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Conway C Huang

Publications and source records attributed to Conway C Huang.

11 recordsLinked to original sources
PubMed2005

KLF4 and PCNA identify stages of tumor initiation in a conditional model of cutaneous squamous epithelial neoplasia.

KLF4 is induced upon growth-arrest in vitro and during epithelial maturation in vivo, and is essential for proper cell fate specification of post-mitotic cells. In spite of a normal role in post-mitotic cells, expression is upregulated and constitutive in certain tumor types. KLF4 functions as an oncogene in vitro, and enforced expression in basal cells of mouse skin rapidly induces lesions similar to hyperplasia, dysplasia and squamous cell carcinoma (SCC). Here we used conditional expression to characterize early steps in KLF4-mediated tumor initiation. In contrast to SCC-like lesions that result when using a conditional, keratin 14 promoter-dependent strategy, lower conditional expression achieved using a MMTV promoter induced only epidermal cycling within morphologically normal skin, a process we termed occult cell turnover. Surprisingly, KLF4-induced hyperplastic lesions showed increased transgene-derived mRNA and protein in maturing, PCNA-negative cells, a property of endogenous KLF4. In contrast, hyperplastic lesions induced by GLI1, a control, showed uniform transgene expression. In KLF4-induced dysplasia and SCC the complementarity of KLF4 and PCNA was replaced by concordance of the two proteins. These studies show that KLF4 transcripts are normally suppressed in cycling cells in a promoter-independent fashion, consistent with a post-transcriptional control, and reveal loss of this control in the transition from hyperplasia to dysplasia. Like the mouse tumors, human cutaneous SCCs and adjacent dysplasias frequently showed maturation-independence of KLF4, with co-expression of KLF4 and PCNA. A smaller subset of human SCCs showed complementarity of KLF4 and PCNA, similar to hyperplastic mouse skin. The results identify parallels between a mouse model and human primary tumors, and show that successive increases of KLF4 in the nuclei of basal keratinocytes leads to occult cell turnover followed by hyperplasia, dysplasia, and invasive SCC.

Animals↗
PubMed2005

Microstaging accuracy after subtotal incisional biopsy of cutaneous melanoma.

BACKGROUND: A significant portion of cutaneous melanoma may remain after subtotal incisional biopsy. The accuracy of microstaging and impact on clinical practice in this scenario are unknown. OBJECTIVE: Our purpose was to examine microstaging accuracy of an initial incisional biopsy with a significant portion of the clinical lesion remaining (> or =50%). METHODS: Patients with cutaneous melanoma, diagnosed by incisional biopsy with > or =50% of the lesion remaining, were prospectively evaluated for microstaging accuracy, comparing initial Breslow depth (BD1) to final depth (BD2) after excision of the residual lesion. Impact on prognosis and treatment was also evaluated. RESULTS: Two hundred fifty of 1783 patients (14%) presented with > or =50% residual clinical lesion after incisional biopsy. The mean BD1 was 0.66 mm; the mean BD2, 1.07 mm (P = .001). After complete excision of the residual lesion, upstaging occurred in 21% and 10% became candidates for sentinel node biopsy. CONCLUSION: An incisional biopsy with > or =50% clinical lesion remaining afterward may be inadequate for accurate microstaging of melanoma. This scenario is relatively uncommon but clinically significant.

Aged↗
PubMed2004

Randomized, controlled surgical trial of preoperative tumor curettage of basal cell carcinoma in Mohs micrographic surgery.

BACKGROUND: The use of preoperative tumor curettage in Mohs micrographic surgery has never been prospectively systematically assessed. OBJECTIVE: To assess the utility of preoperative tumor curettage in Mohs micrographic surgery for primary or recurrent, well-defined basal cell carcinoma less than 2 cm in diameter located on the head or neck. METHODS: Patients were randomized to either preoperative tumor curettage or control group and were compared in terms of percent surface area increase from tumor surface area to wound surface area, absolute surface area increase, number of tissue layers removed, types of repairs performed, and postoperative complications. Multivariate analysis was performed to see if tumor location, appearance (exophytic or flat), or histology affected any of the above. RESULTS: The preoperative tumor curettage group had a 399% (95% confidence interval [CI] 346-452) mean surface area increase from tumor to wound surface area versus 263% (95% CI 216-311) for control group (P=.0002). The preoperative tumor curettage group had a mean absolute surface area increase of 1.78 cm2 (95% CI 1.57-1.99) versus 1.40 cm2 (95% CI 1.15-1.65) for control group (P=.02). The preoperative tumor curettage group had fewer tissue layers removed (P=.3). Preoperative tumor curettage had no effect on types of repairs performed or number or type of postoperative complications. Tumor appearance and histology had no effect on any of the above end points. CONCLUSION: Preoperative tumor curettage was associated with significantly greater percent surface area increase and absolute surface area increase from tumor surface area to wound surface area. This difference did not affect type of repair performed or postoperative complications.

Basal Cell Carcinoma↗
PubMed2004

Surgical margins of excision for basal cell carcinoma and squamous cell carcinoma.

In excising basal and squamous cell carcinomata, the surgical margin that is wide enough to completely remove the tumor an acceptable percentage of the time and narrow enough to minimize removal of excessive normal tissue must be selected. This task can be reliably accomplished with comprehensive knowledge of factors that affect subclinical tumor extension such as tumor appearance, diameter, histology, location, treatment status, and, in the case of squamous cell carcinoma, vertical invasion depth and involvement of subcutaneous fat. Information regarding these factors along with specific recommendations about excisional margins for basal cell and squamous cell carcinomata is presented.

Basal Cell Carcinoma↗
PubMed2004

Dry eyes and superficial punctate keratitis: a complication of treatment of glabelar dynamic rhytides with botulinum exotoxin A.

BACKGROUND: Dry eyes and superficial punctate keratitis are potential complications of periocular botulinum exotoxin A treatment. OBJECTIVE: To report a patient who had these side effects after being treated with botulinum exotoxin A for glabelar rhytides and discuss possible causes including excessive paralysis of the orbicularis oculi leading to lagophthalmos and direct paralysis of the lacrimal gland. METHODS: A case report and brief literature review is presented. CONCLUSION: Paralytic lagophthalmos caused dry eyes and superficial punctate keratitis in our patient. To avoid this complication, if an injection is to be done in the lateral brow area, it should be done 1 cm above the orbital rim.

Botulinum Toxins, Type A↗
PubMed2004

Pyogenic granuloma caused by exposed sternotomy wires.

BACKGROUND: This case describes a 75-year-old African American man who developed a pyogenic granuloma on the chest due to trauma induced by exposed sternotomy wires from his coronary bypass procedure. OBJECTIVE: To describe a previously unreported cause of pyogenic granuloma. MATERIALS AND METHODS: The pyogenic granuloma was excised and during the procedure, exposed sternotomy wires were uncoiled at the base of the lesion. The sternotomy wires were retightened and reappositioned along the sternum, and the wound was closed primarily. RESULTS: The pyogenic granuloma has not recurred after 15 months of follow-up. CONCLUSIONS: Pyogenic granulomas are vascular benign tumors that commonly appear secondary to trauma. The source of the trauma in this case was the exposed sternotomy wires.

Aged↗
PubMed2002

Comparative gene expression profile analysis of GLI and c-MYC in an epithelial model of malignant transformation.

Transcription factor oncogenes such as GLI and c-MYC are central to the pathogenesis of human tumors. GLI encodes a zinc finger protein that is activated by Sonic Hedgehog signaling. Mutations in this pathway induce GLI expression in basal cell carcinoma, and expression of GLI in mice is sufficient to induce these skin tumors. We used microarrays to identify transcripts regulated by GLI or c-MYC after retroviral transduction and short-term culture of epithelial RK3E cells. Although each of these oncogenes induces malignant transformation of RK3E, two distinct sets of genes were identified. Of approximately 17,500 transcripts represented on the microarrays, GLI up-regulated the expression of 158 and repressed the expression of 52. In contrast, transcripts regulated by c-MYC were mainly repressed (424 of 682 regulated transcripts). Transcripts induced by the GLI transgene are likewise expressed in association with endogenous GLI in Ptch-deficient murine fibroblasts or in human skin tumors, but are not up-regulated in RK3E cells transformed by c-MYC, KLF4, or HRAS1. Unlike these other oncogenes, GLI induced the expression of mesenchymal cell markers including Snail, a zinc finger protein implicated in epithelial-mesenchymal transition in development and during tumor progression. A novel GLI-estrogen receptor fusion protein rapidly induced Snail mRNA expression in a manner like Ptch, a known direct transcriptional target gene. Induction of Snail expression and epithelial-mesenchymal transition by GLI may account for certain histopathological features of basal cell carcinoma, such as the absence of a well-defined, intraepithelial precursor lesion. In addition, consistent expression of the newly identified GLI-induced transcripts within GLI-expressing tumors in vivo indicates that oncogene-specific transcriptional profiles may be useful diagnostic tools for analysis of human tumors.

Animals↗