Hamm-Ming Sheu - Academia.edu (original) (raw)

Papers by Hamm-Ming Sheu

Journal of dermatological science, 2015

Previous studies have shown that human sebum may play a role in barrier function but with much de... more Previous studies have shown that human sebum may play a role in barrier function but with much debate. To elucidate the effects of human sebum on skin barrier function. We used hairless mouse skin to study the functional and morphological alternation of epidermis after the application of human sebum. The results showed a significant increase in transepidermal water loss and erythema value, and a decrease in skin hydration, accompanied by epidermal hyperplasia with parakeratosis following sebum application. Nile red staining together with electron microscopic examination confirmed the underlying mechanisms for sebum-induced barrier disruption are related directly to the interaction of sebum with the intracellular lipid lamellae of the SC, thereby leading to the increase in the fluidity of SC intracellular lipids as demonstrated by ATR-FTIR measurement. An inflammatory reaction characterized by an enhanced cytokine cascade, including up-regulation of TNF-α, IL-1α and IL-6, was also ob...

Chemical Research in Toxicology, 2008

We have previously demonstrated that solamargine (SM), the major steroidal glycoalkaloid extracte... more We have previously demonstrated that solamargine (SM), the major steroidal glycoalkaloid extracted from Chinese herb Solanum plants, reveals down-regulation of HER2 and up-regulation of Fas and tumor necrosis factor receptor (TNFR) expressions, triggers the mitochondria-mediated cell apoptosis pathway, and sensitizes human nonsmall cell lung cancer (NSCLC) H441 and A549 adenocarcinoma cells to chemotherapy. The present study shows that SM enhances HER2 expression in NSCLC large cell carcinoma H661 and small cell lung cancer (SCLC) H69 cells and may increase the susceptibility of the cells to trastuzumab, the humanized anti-HER2 antibody. The combinational treatment of SM and trastuzumab synergistically augments and inhibits H661 and H69 cell proliferation. After treatment with SM, coexpression of HER2 and topoisomerase IIalpha (TOP2A) H661 and H69 cells is more sensitive to the TOP2 inhibitor, epirubicin. The combinatory use of low concentrations of SM with the low-toxic epirubicin accelerated greater apoptotic cell death than each drug did alone in H661 and H69 cells. Relevant studies have shown that HER2 overexpressing cancer cells are more resistant than HER2 low-expressing cells to the chemotherapeutic agent and tumor necrosis factor-induced apoptosis. These investigations have indicated that HER2 overexpression does not suffice to induce intrinsic and pleomorphic drug resistance. The data presented herein suggest that the expression of HER2 did not influence the SM-induced apoptosis of different types of lung cancer cells and that the SM up-regulation of HER2 and TOP2A expressions simultaneously augmented trastuzumab and epirubicin-induced deaths of lung cancer H661 and H69 cells.

Journal of …, 2011

Background: The Solanum species herbs have been used to treat cancer for centuries; however, the ... more Background: The Solanum species herbs have been used to treat cancer for centuries; however, the underlying mechanisms and effectiveness in vivo remain unclear. Objectives: SR-T100, extracted from the Solanum incanum, contains solamargine alkaloid as the main active ingredient. Here, we investigated the apoptosis-inducing effects of SR-T100 for targeting squamous cell carcinoma (SCC) in vitro and in vivo. Methods: We elucidated the mechanism by which SR-T100 induces apoptosis of human SCCs (A431, SCC4, SCC9, and SCC25) cells. The efficacy and safety issues were addressed regarding topical treatment of SR-T100 on UVB-induced cutaneous SCC of hairless mice and actinic keratoses (AKs) of human. Results: SR-T100 induces apoptosis in human SCCs cell lines by up-regulating the expressions of tumor necrosis factor receptors (TNFRs) and Fas, and downstream adaptors FADD/TRADD of the TNF-a and Fas ligand signaling cascades. SR-T100 also triggered the mitochondrial apoptotic pathway, as up-regulated cytochrome c and Bax, down-regulated Bcl-X L. Animal experiments showed that all papillomas (35/35) and 27 of 30 UVB-induced microinvasive SCCs in hairless mice disappeared within 10 weeks after oncedaily application of topical SR-T100. Furthermore, 13 patients, who suffered with 14 AKs, were treated with once-daily topical SR-T100 gel and 10 AKs cured after 16 weeks, showing negligible discomforts. Conclusion: Our studies indicate that SR-T100 induces apoptosis of SCC cells via death receptors and the mitochondrial death pathway. The high efficacy of SR-T100 in our preclinical trial suggests that SR-T100 is a highly promising herb for AKs and related disorders.

Dermatologica Sinica, 2015

Pharmaceutical research, 2003

To investigate the mechanisms underlying the regional variations in drug transport into human str... more To investigate the mechanisms underlying the regional variations in drug transport into human stratum corneum (SC) of two model compounds of different lipophilicity and molecular size, 4-cyanophenol (CP) and cimetidine (CM), in vivo by non-invasive, quantitative attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy. Saturated solutions of CP and CM were applied to the skin surface of eleven Chinese men, at five anatomical sites, including forearm, back, thigh, leg, and abdomen, for 10-15 min and 3-5 h, respectively. After the skin surface was cleansed of remaining chemicals, the SC was tape-stripped sequentially up to 20 times, and the drug concentration profiles in the tape-stripped SC were determined using ATR-FTIR spectroscopy. Thickness of the SC was estimated simultaneously using two-point measurements of transepidermal water loss before and after completion of tape stripping. Estimation of partition, diffusion, and permeability coefficients was achiev...

The Journal of dermatology, 1991

The expression of the various markers for terminal epidermal differentiation in atrophic skin of ... more The expression of the various markers for terminal epidermal differentiation in atrophic skin of patients after long-term topical corticosteroids (TCS) was studied by electron microscopy, immunofluorescence using antibody to profilaggrin/filaggrin (PF/FG), immunoperoxidase staining using antibody to involucrin, and oil red O stain for neural lipids of the stratum corneum. Thirty-nine patients were subdivided into two groups: (A) 19 patients suffering from rebound phenomenon after stopping TCS and (B) 20 patients without rebound phenomenon. Biopsy specimens were taken before ending the use of TCS in both groups. In group A, both the morphological markers (including the different epidermal strata, keratohyalin granules, lamellar granules, and cornified cell envelopes) and the molecular markers (including involucrin, PF/FG, and neutral lipids) of terminal epidermal differentiation were significantly suppressed. On the other hand, the differentiational markers in the atrophic skin of pa...

International Journal of Dermatology, 2006

The vesicular variant of bullous pemphigoid is a clinical entity in which the principal type of l... more The vesicular variant of bullous pemphigoid is a clinical entity in which the principal type of lesions are multiple small tense vesicles in a symmetric distribution, instead of the classical large, more randomly distributed large bullae. We describe a 62-year-old female who developed a vesicular variant of bullous pemphigoid, with intensely pruritic vesiculopapular eruptions and erythematous irregularly outlined patches confluent on the face, neck, trunk, extremities and oral mucosa. Direct immunofluorescence revealed a linear deposition of IgG and C3 at the basement membrane zone of the skin, and indirect immunofluorescence detected circulating IgG autoantibodies reacting with antigens located on the epidermal side of skin split with 1 M NaCl. Indirect immunogold electron microscopy revealed IgG deposition at the underneath membrane of the basal cells and in the lamina lucida. In addition to the 230-kDa and 180-kDa bullous pemphigoid antigen, immunoblot analysis also demonstrated the presence of IgG antibodies reactive with 97-kDa and 45-kDa protein. Treatment with systemic corticosteroid, minocycline and antihistamines plus topical steroid resulted in moderate improvement. A few vesicles, however, continued to appear intermittently during the past year of treatment.

Experimental dermatology, 2015

Adipose tissue encircles the lower portion of anagen hair follicles and may regulate hair cycle p... more Adipose tissue encircles the lower portion of anagen hair follicles and may regulate hair cycle progression. As leptin is a major adipokine, its level of expression from the dermal white adipose tissue during hair cycle progression was studied. The result shows that leptin level is differentially expressed during hair cycle, the lowest in early anagen phase, upregulated in late anagen phase and the highest in the telogen phase. On the other hand, leptin receptor is detected in keratin 15-positive hair bulge epithelium of both anagen- and telogen-phase hair follicles of mice pelage and vibrissa hair, and hair from human scalp. Leptin contributes to adipocyte-mediated growth inhibition of anagen-phase vibrissa hair as demonstrated in organ culture and coculture system. Our data suggest that leptin of dermal white adipose tissue might regulate hair growth and, therefore, hair cycle progression via leptin receptor on the hair follicle epithelium.

Annals of Dermatology, 2013

Background: Spontaneous recovery of severe alopecia areata is rare and the condition is difficult... more Background: Spontaneous recovery of severe alopecia areata is rare and the condition is difficult to treat. Objective:

PLoS ONE, 2014

Chromium hypersensitivity (chromium-induced allergic contact dermatitis) is an important issue in... more Chromium hypersensitivity (chromium-induced allergic contact dermatitis) is an important issue in occupational skin disease. Hexavalent chromium (Cr (VI)) can activate the Akt, Nuclear factor kB (NF-kB), and Mitogen-activated protein kinase (MAPK) pathways and induce cell death, via the effects of reactive oxygen species (ROS). Recently, cell death stimuli have been proposed to regulate the release of inflammatory cytokines, such as tumor necrosis factor-a (TNF-a) and interleukin-1 (IL-1). However, the exact effects of ROS on the signaling molecules and cytotoxicity involved in Cr(VI)-induced hypersensitivityhave not yet been fully demonstrated. N-acetylcysteine (NAC) could increase glutathione levels in the skin and act as an antioxidant. In this study, we investigated the effects of NAC on attenuating the Cr(VI)-triggered ROS signaling in both normal keratinocyte cells (HaCaT cells) and a guinea pig (GP) model. The results showed the induction of apoptosis, autophagy and ROS were observed after different concentrations of Cr(VI) treatment. HaCaT cells pretreated with NAC exhibited a decrease in apoptosis and autophagy, which could affect cell viability. In addition, Cr (VI) activated the Akt, NF-kB and MAPK pathways thereby increasing IL-1a and TNF-a production. However, all of these stimulation phenomena could be inhibited by NAC in both of in vitro and in vivo studies. These novel findings indicate that NAC may prevent the development of chromium hypersensitivity by inhibiting of ROS-induced cell death and cytokine expression.

Urology, 2003

Objectives. Penile verrucous carcinoma is characterized by aggressive local growth and a low meta... more Objectives. Penile verrucous carcinoma is characterized by aggressive local growth and a low metastatic potential. Lower abdominal aortic infusion chemotherapy has the main advantage of delivering a very high concentration of an anticancer drug to the whole pelvic area, including the penis, and is especially suitable to treat penile verrucous carcinoma. Methods. From 1991 to 2000, 4 cases of penile verrucous carcinoma were treated by continuous intra-aortic infusion with methotrexate (50 mg) every 24 hours, for an average of 10 days. Citrovorum factor (6 mg) was given intramuscularly every 6 hours during the period of methotrexate infusion. Results. After treatment, 3 patients achieved complete remission. They were living disease free 10 years, 10 months, 6 years, 9 months, and 1 year, 8 months after therapy. Conclusions. Intra-aortic infusion chemotherapy is a simple and effective method for penile verrucous carcinoma with the unique advantage of preserving cosmetic and functional integrity. It may be considered an effective alternative treatment for penile verrucous carcinoma. By using this simple method many unnecessary penectomies can be avoided. UROLOGY 61: 1216-1220, 2003.

Trends in Molecular Medicine, 2007

Common fragile site gene WWOX encodes a candidate tumor suppressor WW domain-containing oxidoredu... more Common fragile site gene WWOX encodes a candidate tumor suppressor WW domain-containing oxidoreductase. Alteration of this gene, along with dramatic downregulation of WWOX protein, is shown in the majority of invasive cancer cells. Ectopic WWOX exhibits proapoptotic and tumor inhibitory functions in vitro and in vivo, probably interacting with growth regulatory proteins p53, p73 and others. Hyaluronidases regulate WWOX expression, increase cancer invasiveness and seem to be involved in the development of hormone-independent growth of invasive cancer cells. Estrogen and androgen stimulate phosphorylation and nuclear translocation of WWOX, although binding of WWOX to these sex hormones is unknown. We propose that suppression of WWOX expression by overexpressed hyaluronidases might contribute in part to the development of hormone independence in invasive cancer.

Toxicology Letters, 2010

19 Chromium hypersensitivity 20 Mitogen-activated protein kinase 21 Nuclear factor B 22 Tumor nec... more 19 Chromium hypersensitivity 20 Mitogen-activated protein kinase 21 Nuclear factor B 22 Tumor necrosis factor-␣ 23 a b s t r a c t

The Kaohsiung Journal of Medical Sciences, 2013

The Journal of Urology, 2010

Traditional treatment for advanced penile verrucous carcinoma is penectomy. This mostly leads to ... more Traditional treatment for advanced penile verrucous carcinoma is penectomy. This mostly leads to remarkable psychosexual problems and greatly affects quality of life, especially in young patients. To preserve the penis we used intra-aortic infusion chemotherapy for advanced verrucous carcinoma. From 1991 to 2009 we treated 6 men with penile verrucous carcinoma with continuous intra-aortic infusion of 50 mg methotrexate every 24 hours (average 550 mg, range 400 to 800). Citrovorum factor (6 mg) was given intramuscularly every 6 hours during methotrexate infusion. After continuous methotrexate infusion no further anticancer drug was given to complete responders. Partial responders subsequently received long-term, intermittent, intra-aortic infusion of 50 mg methotrexate or 2 mg mitomycin C plus 250 mg 5-fluorouracil every 1 to 2 weeks until tumors disappeared and all wounds healed. After treatment 4 patients achieved a complete response and were disease-free 3 years 9 months to 17 years 10 months (median 11 years 3 months) after therapy. Two patients had a partial response. The patient with a shaft tumor subsequently underwent total penectomy due to unbearable penile pain 4 years after infusion with various drugs without an appreciable response. He has survived 12 years 5 months after initial treatment. The other patient with glans and prepuce tumors had progression with bilateral inguinal metastases despite 1 1/2 years of infusion therapy. Total penectomy was done. Histological examination of the glans mass revealed moderately differentiated squamous cell carcinoma. Patient condition progressed rapidly and he died 11 months after penectomy. Intra-aortic infusion chemotherapy is a simple, effective method to treat penile verrucous carcinoma with the uniqueness of preserving the anatomical structure and sexual function in complete responders. For penile verrucous carcinoma, especially in younger patients, intra-aortic infusion chemotherapy may be considered organ sparing treatment before penectomy.

Journal of the American Academy of Dermatology, 2014

Background: Obesity is a risk factor for multiple health problems, but its association with andro... more Background: Obesity is a risk factor for multiple health problems, but its association with androgenetic alopecia (AGA) remains controversial.

Journal of the American Academy of Dermatology, 2013

Journal of Pharmaceutical Sciences, 2001

The permeability of compromised skin barrier was investigated in vitro using acetone-disrupted ha... more The permeability of compromised skin barrier was investigated in vitro using acetone-disrupted hairless mouse skin as a model membrane. The effect of compound lipophilicity was studied using sucrose, caffeine, hydrocortisone, estradiol, and progesterone as model compounds. The results demonstrated that permeability barrier disruption by acetone treatment signi®cantly enhanced the permeability of the skin to both hydrophilic and amphipathic compounds, including sucrose, caffeine and hydrocortisone. This effect was more prominent with caffeine and hydrocortisone at different transepidermal water loss (TEWL) levels. Acetone treatment, however, didn't appear to alter the percutaneous penetration of highly lipophilic compounds, such as estradiol and progesterone. The characteristics of skin permeability were described by parabolic relationships between log P WS (permeability coef®cient of whole skin) and log K O/W (octanol/water partition coef®cient) at different degrees of permeability barrier disruption. The optimal log K O/W of compounds for skin penetration appeared to decrease with an increase in TEWL levels. The maximal permeability achieved was similar through skin displaying different TEWL levels. In an attempt to explore the underlying mechanisms for the changes in skin permeability, the stratum corneum/ normal saline partition coef®cients of water, caffeine, and hydrocortisone either decreased or remained unaffected with an increase in TEWL. Electron microscopic examinations have revealed reductions in stratum corneum lipid content and alterations in intercellular membrane structures as a result of acetone treatment, whereas negligible changes in the number of horny layers were observed by safranin staining of the stratum corneum. We have concluded that the enhancement in skin permeability to both hydrophilic and amphipathic compounds by acetone treatment arose mainly because of the increase in stratum corneum diffusivity at higher TEWL levels. The results imply the possibility of using both TEWL and drug lipophilicity to predict alterations in skin permeability and hence the dose adjustment of topically applied medication for patients with impaired skin barrier function. ß

Journal of Pharmaceutical Sciences, 2004

The United States Food and Drug Administration recommends pilot dose duration-response and pivota... more The United States Food and Drug Administration recommends pilot dose duration-response and pivotal bioequivalence studies to be conducted using reflectance colorimetry for assessment of the in vivo bioequivalence of topical dermatologic corticosteroids. The major objectives of the present studies were to examine the applicability of the standardized pharmacodynamic modeling-based methodology to super-potent clobetasol 17-propionate (CP) in the Chinese population and to evaluate the bioequivalence of two generic ointments and four generic creams containing 0.05% (w/w) CP with respect to Dermovate formulations using such methodology. In the pilot dose duration-response study, although the E max model (where E max is the maximum fitted value of AUEC, which is the area under the baseline-corrected, untreated control-sitecorrected a* scale data from 0 to 24 h after drug removal) did not provide acceptable model fits, E max parameter estimates of À38.97 AE 3.62 and À41.89 AE 11.28 a*-scale Á h, and ED 50 (dose duration required to achieve 50% of the fitted E max value) estimates of 0.40 AE 0.37 and 0.42 AE 0.16 h were obtained for Dermovate ointment and cream, respectively, by population analyses. The estimates for the two formulations were not statistically different, so in vivo bioequivalence studies were conducted at an ED 50 dose duration of $0.5 h for both Dermovate formulations. The results demonstrated that one generic ointment was bioequivalent to Dermovate, whereas the other was not. None of the generic creams were shown to be bioequivalent to Dermovate cream. The in vivo bioequivalence data from the vasoconstriction assay were linearly correlated with stratum corneum uptake of the drug at the same dose duration until the maximal vasoconstriction response was achieved. The studies illustrated the applicability of the standardized pharmacodynamic modeling-based methodology in detecting the product differences between a variety of generic 0.05% CP formulations and reference Dermovate formulations in Chinese skin. ß

Journal of Investigative Dermatology, 2008

The prevalence of childhood eczema is increasing in many countries. Epidemiological studies, howe... more The prevalence of childhood eczema is increasing in many countries. Epidemiological studies, however, say little of its association to outdoor air pollution and climate factors. We conducted a nationwide survey of middle-school students in Taiwan from 1995 to 1996. The 12-month prevalence of eczema was compared with air monitoring station data of temperature, relative humidity, and criteria air pollutants. A total of 317,926 children attended schools located within 2 km of 55 stations. Prevalence rates of recurrent eczema were 2.4 and 2.3% in boys and girls, respectively, with prevalence rates of flexural eczema 1.7% in both sexes. After adjustment for possible confounders, flexural eczema was found to be associated with traffic-related air pollutants, including nitrogen oxides and carbon monoxide. Recurrent eczema was associated with traffic-related air pollution only in girls. There were no associations for the highest monthly means of temperature, whereas the annual means and the lowest monthly means of temperature were negatively related to flexural eczema, but only in girls. The lowest monthly mean relative humidity was positively related to eczema. The results suggest that air pollution and climatic factors, which showed stronger associations in girls than boys, may affect the prevalence of childhood eczema.