PubMed Health⌕ Search

Biomedical subjects

H Tsao

Publications and source records attributed to H Tsao.

At least 19 recordsLinked to original sources
PubMed2001

Evidence for an association between cutaneous melanoma and non-Hodgkin lymphoma.

BACKGROUND: Over the past 2 decades both cutaneous melanoma (CM) and non-Hodgkin lymphoma (NHL) incidence rates have increased substantially. One approach to better understanding the etiologic basis for these increases is to examine the risk of NHL in CM survivors and the risk of CM in NHL survivors. METHODS: To explore the possible association between CM and NHL, the authors followed cohorts of CM and NHL patients registered through the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program between 1973 and 1996 and identified patients who developed CM after NHL and NHL after CM. The number of observed cases then were compared with the number of expected cases to see if CM survivors were at an increased risk of NHL or if NHL survivors were at an increased risk of CM. RESULTS: Between 1973 and 1996, 54,803 CM patients and 62,597 NHL patients who met the authors' inclusion criteria were identified through SEER. The authors found statistically significant elevated risks of NHL among CM survivors (standardized incidence ratio [SIR], 1.42; 95% confidence interval [CI], 1.23-1.63) and CM among NHL survivors (SIR, 1.75; 95% CI, 1.48-2.07). CONCLUSIONS: These results support an association between CM and NHL. Although detection bias and posttherapy effects may explain part of this association, shared genetic or etiologic factors, such as sunlight exposure, also may play a role.

Female↗
PubMed2001

Effect of stent on radiation dosimetry in an in-stent restenosis model.

Purpose: Intravascular brachytherapy is the leading modality being evaluated for treatment of in-stent restenosis. Stent struts may have an effect on the dose distributions of various radiation sources. We evaluated dosimetry in a stented coronary artery model using a variety of beta and gamma sources and stent materials.Methods: We determined the dose distributions with and without stent in the in-stent restenosis model. Three beta-particle emitting radionuclides, 90Y (2.3 MeV), 144Pr (3.0 MeV), and 106Rh (3.5 MeV), and two gamma-ray emitters, 192Ir (380 keV) and 125I (30 keV), were studied. Stent materials included stainless steel, nitinol, and tantalum. Monte Carlo dose calculations were performed in a stent model of multiple stent struts placed at 1.5 mm from the source. Isodose curves were generated and the ratios of dose rates with and without stent, the stent factors, were evaluated. A stent factor of greater or less than unity represents dose enhancement or reduction in the presence of a stent.Results: For the three beta radionuclides, dose reduction was found on the adventitial side of the stent strut and dose enhancement was noted on the luminal side. On the luminal side, the maximum dose enhancement ranges from 7% to 29%, and the dose reduction on the adventitial side ranges from 13% to 43%. Both the reduction and enhancement effects were most pronounced for the high atomic number material, tantalum. For a given stent material, the dose reduction and enhancement are similar for the three beta radionuclides. For the gamma sources, the stent had no effect for the high-energy 192Ir, but for the low-energy 125I, drastic dose reduction on the adventitial side was observed (up to 86% for tantalum stent), and about 10% dose enhancement on the luminal side was also noted. The dose reduction with 125I was more pronounced than that seen with the beta sources.Conclusions: The presence of stent struts significantly affects dose distributions of 90Y, 106Rh, 144Pr, and 125I. The maximum dose reduction can be as much as 86%. 192Ir was unaffected. These factors need to be considered in choosing radionuclides and dose prescriptions in treating in-stent restenosis.

Journal Article↗
PubMed2001

Genetics of nonmelanoma skin cancer.

Cancer is in essence a genetic disease characterized by genomic instability. Unlike classic genetic syndromes in which a single inherited mutation is often sufficient to determine the perturbed phenotype, most cancers, especially solid tumors, develop after an accumulation of multiple genetic lesions. Inherited mutations that predispose individuals to cancer formation are termed germline, while acquired mutations that contribute to tumor development are designated somatic. Bona fide hereditary cancers account for only a small proportion of all documented cancers. Most tumors result from mutations caused by inherent infidelities in DNA replication, carcinogens, or defects in the DNA reparative apparatus. When mutations occur in critical growth regulatory genes, variations in cellular proliferation and survival contribute to the selection of dominant tumor population(s). Furthermore, these mutations may alter the antigenic properties of the cancerous cell and encourage escape from the host response. Thus, cancer is evolution at the microscopic level.

Carcinoma, Adenoid Cystic↗
PubMed2001

A meta-analysis of reverse transcriptase-polymerase chain reaction for tyrosinase mRNA as a marker for circulating tumor cells in cutaneous melanoma.

OBJECTIVE: To systematically review the use of reverse transcriptase-polymerase chain reaction (RT-PCR) for tyrosinase messenger RNA as a molecular serum marker for metastatic melanoma. DATA SOURCES: Computerized searches (1966-1999) of the PubMed and MDConsult databases and a manual search of retrieved article references. STUDY SELECTION: Cohort studies containing test subjects and negative controls were reviewed. DATA EXTRACTION: Three investigators independently screened abstracts for relevant studies and 2 investigators independently reviewed all eligible studies. DATA SYNTHESIS: Of 127 identified studies, 50 were reviewed in detail and 23 met all inclusion criteria. From these 23 studies, the PCR methods, the total number of patients, the number of control subjects, and the number of RT-PCR-positive patients per stage were analyzed. Results of RT-PCR for tyrosinase messenger RNA were positive in 18% (95% confidence interval [CI], 3%-22%) patients for stage I disease, 28% (95% CI, 23%-34%) for stage II disease, 19% (95% CI, 16%-21%) for stage I/II localized disease, 30% (95% CI, 26%-34%) for stage III disease, and 45% (95% CI, 41%-50%) for stage IV disease. Specificities were 100% in all but 1 study. Results of RT-PCR were positive in only 0.4% of healthy controls and patients with nonmelanoma cancer. CONCLUSIONS: The lack of data on the outcome of stage I, II, and III patients who were RT-PCR positive and the low prevalence of RT-PCR positivity in patients with known stage IV disease limit the applicability of this test at this time. Ongoing and future studies on a quantitative RT-PCR, amplification of multiple melanoma-associated antigens, and use of the test as a prognostic indicator might improve the utility of this molecular serologic tool.

Biomarkers, Tumor↗
PubMed2000

Relative reciprocity of NRAS and PTEN/MMAC1 alterations in cutaneous melanoma cell lines.

Both inactivation of the tumor suppressor gene, PTEN/MMAC1, and oncogenic activation of RAS have been described in human cutaneous melanoma. In mice, activation of a RAS-containing pathway is a necessary step in the pathogenesis of murine melanomas. Because PTEN negatively regulates on the downstream effects of phosphatidylinositol-3-kinase (PI3-K), we hypothesized that the loss of PTEN/MMAC1 and the activation of RAS may be largely equivalent because RAS is a known positive upstream regulator of PI3-K. We expanded our previous survey of PTEN/MMAC1 mutations and analyzed the RAS status of 53 cutaneous melanoma cell lines, 18 glioma cell lines, and 17 uncultured cutaneous melanoma metastasis. Overall, 51% of the cell lines had alterations in either PTEN/MMAC1 or RAS. We found 16 cell lines (30%) with alterations in PTEN/MMAC1 and 11 cell lines (21%) with activating NRAS mutations; only 1 cell line had concurrent alterations in both genes. Moreover, glioma cell lines with a high frequency of PTEN/MMAC1 inactivation had no identifiable RAS alterations. Ectopic expression of PTEN in several cutaneous melanoma cell lines suppressed colony formation irrespective of PTEN/MMAC1 status; furthermore, PTEN expression in cell lines carrying activated RAS also suppressed colony formation. The relative reciprocity of PTEN/MMAC1 abrogation and NRAS activation suggests that the two genetic changes, in a subset of cutaneous melanomas, are functionally overlapping.

Alternative Splicing↗
PubMed2000

Low prevalence of germline CDKN2A and CDK4 mutations in patients with early-onset melanoma.

BACKGROUND: In patients with cutaneous melanoma, early age at disease onset is characteristic in familial cases and in individuals with multiple primary melanomas. Both subsets of patients with melanoma are at risk for harboring germline CDKN2A or CDK4 mutations. OBJECTIVE: We set out to prospectively determine the prevalence of CDKN2A and CDK4 mutations in a group of young patients with melanoma. DESIGN: We prospectively screened 913 patients over a 6-month period and identified 519 patients with invasive melanomas. We invited 172 patients with melanoma who were younger than 40 years to participate in the study, and 49 patients consented and donated peripheral blood samples. Forty-nine percent (n = 24) of our patients developed cutaneous melanoma before the age of 30 years. SETTING: A melanoma clinic in the Boston, Mass, area. MAIN OUTCOME MEASURE: We used a combination of single-strand conformation analysis and direct sequencing of samples of peripheral blood leukocyte DNA to search for mutations in exons 1alpha, 1beta, 2, and 3 of CDKN2A and in exon 2 of CDK4. RESULTS: The mean and median ages at diagnosis in our group were 30 and 32 years, respectively. Among a group of 49 patients, we detected 1 (2%; 95% confidence interval, 0.07%-10.8%) Met 53 Ile CDKN2A mutation, which was found in a patient with a strong family history of melanoma. This alteration has been previously shown to impair p16 function. One patient had an Ala 148 Thr change in CDKN2A, which has also been shown to be a polymorphism. We also detected a sequence polymorphism (in the 3' untranslated region [3'UTR] of CDKN2A) in 27% of our patients. A similar incidence of this 3'UTR polymorphism was observed in a control population. We found no CDK4 mutations. CONCLUSIONS: Germline CDKN2A and CDK4 mutations are not common in patients who develop melanoma at an early age. This finding contrasts with other cancer-predisposition syndromes, in which there is an increased incidence of germline mutations among young patients. Selection of patients with melanoma for genetic testing based solely on age at onset may not be warranted at the current time.

Adolescent↗
PubMed2000

Pigmented purpuric eruption associated with injection medroxyprogesterone acetate.

Pigmented purpuric eruptions are characterized clinically by purpura, most commonly petechial, and brownish pigmentation. Although there are several idiopathic variants, several drugs have been associated with these eruptions. We present a patient who experienced pigmented purpura on her lower extremities several months after initiating medroxyprogesterone acetate injection. The eruption cleared several weeks after discontinuation of the medication.

Adult↗
PubMed2000

Update on familial cancer syndromes and the skin.

UNLABELLED: Familial cancer syndromes reflect an inherited predisposition to develop benign and malignant tumors. Clinically, the cancers occur at an earlier age and involve multiple foci of tumor formation at multiple sites. In the past 10 years, the molecular basis of many of these cancer syndromes have been unraveled with the advent of powerful genetic technologies. Entities which were hypothesized to be related on the basis of clinical features have now been shown to be linked or disparate through genetic analysis. This article reviews some of the recent advances in the clinical and molecular aspects of familial cancer syndromes that involve the skin. (J Am Acad Dermatol 2000;42:939-69.) LEARNING OBJECTIVE: After completing this article, the reader should become (1) fluent with some basic genetic principles underlying the mechanisms of cancer predisposition and positional cloning and (2) aware of the recent breakthroughs in the identification of familial cancer syndrome disease genes.

Basal Cell Carcinoma↗
PubMed1999

Identification and mutation analysis of DOC-1R, a DOC-1 growth suppressor-related gene.

The tumor suppressor gene MEN1 and several oncogenes including CCND1/cyclin D1/PRAD1 map to chromosome 11q13. However, molecular and cytogenetic analysis suggests the presence of a second tumor suppressor locus at this chromosome region. We have identified a novel gene from chromosome 11q13, which encodes a protein of 126 amino acids sharing an overall 57% identity with the p12(DOC-1) protein encoded by the DOC-1 gene, the human homolog of hamster putative tumor suppressor doc-1 (deleted in oral cancer-1). We therefore designated the novel gene as DOC-1R for DOC-1-related. The cytogenetic location was confirmed by chromosome fluorescent in situ hybridization. Northern blot analysis indicated that it was expressed in all the tissues examined. DOC-1R protein showed heterogeneous subcellular localization. RT-PCR-SSCP analysis failed to detect deleterious mutations of the DOC-1R transcript in four premalignant oral keratinocyte lines and 20 different cancer cell lines from tumor types which frequently harbor LOH at chromosome 11q13.

Amino Acid Sequence↗
PubMed1999

Mutational and expression analysis of the p73 gene in melanoma cell lines.

A novel p53-related gene, p73, was recently isolated and cytogenetically mapped to chromosome region 1p36. Functionally, p73 expression induces p21waf and suppresses tumor cell growth. We mapped p73 using radiation hybrids and localized the gene to an interval that putatively harbors a melanoma tumor suppressor locus. We then analyzed p73 transcripts from 24 melanoma cell lines using reverse transcription-PCR/single strand conformation polymorphism and identified nine polymorphic sequence changes (three novel and six previously published polymorphisms); furthermore, we found evidence of biallelic transcription in our cell lines. However, we did not detect any deleterious mutations. These data suggest that the p73 gene is unlikely to be essential in melanoma tumorigenesis.

Chromosome Mapping↗
PubMed1998

Identification of PTEN/MMAC1 alterations in uncultured melanomas and melanoma cell lines.

A novel tumor suppressor gene, PTEN/MMAC1, has been recently shown to be mutated in gliomas, breast, prostate, kidney cancers and melanomas. Loss-of-heterozygosity studies in melanoma have suggested the presence of at least one chromosome 10q locus lost early in tumor progression. In this study, we screened 45 melanoma cell lines and 17 paired uncultured metastatic melanoma and peripheral blood specimens for PTEN/ MMAC1 alterations using PCR-SSCP and direct sequencing. We found nine melanoma cell lines with homozygous deletions (five with intragenic loss) and four cell lines with mutations (one nonsense and one frameshift; two intronic); from among our uncultured melanoma specimens, we found one tumor with a somatic 17 bp duplication in exon 7 leading to a premature stop codon and one tumor with a possible homozygous deletion. Furthermore, we have identified a novel intragenic polymorphism within intron 4 of PTEN/MMAC1. Taken together, these data suggest that PTEN/MMAC1 may be a chromosome 10q tumor suppressor important in melanoma tumor formation or progression.

Chromosomes, Human, Pair 10↗
PubMed1998

Sequence dependence and characteristics of bends induced by site-specific polynuclear aromatic carcinogen-deoxyguanosine lesions in oligonucleotides.

The tumorigenic metabolite of benzo[a]pyrene, the (+)-7R,8S,9S,10R enantiomer, and the nontumorigenic mirror-image isomer, (-)-7S,8R,9R, 10S, of r7,t8-dihydroxy-t9,10-epoxy-7,8,9, 10-tetrahydrobenzo[a]pyrene (anti-BPDE) bind covalently to the exocyclic amino group of deoxyguanosine (N2-dG) in native DNA. These adducts can cause structural perturbations such as DNA bends, which in turn may influence the cellular processing of these lesions. The characteristics of bends in site-specifically modified oligodeoxyribonucleotide duplexes induced by single (+)- and (-)-anti-[BP]-N2-dG lesions were examined by self-ligation and gel electrophoresis techniques. The modified residues (dG*) were centrally positioned in the 11-mer oligonucleotide d(CACAXG*XACAC) complexed with the natural complementary strands, with X = T or C, or in oligonucleotides 16 or 22 base pairs long with the same centrally positioned 11-mer. Among the four stereochemically distinct lesions, the 10S(+)-trans-anti-[BP]-N2-dG adducts were significantly more bent than any of the other three stereoisomeric adducts and were selected for detailed studies. In the TG*T sequence context (X = T), the retardation factor RL (apparent length of multimer/sequence length) is approximately independent of the phasing (distance, in base pairs, between the lesions) of the adducts with respect to the helical repeat (10.5 base pairs/helix turn). In contrast, in the CG*C sequence context (X = C), RL is markedly lower in the case of ligated 16-mers than in the case of ligated 11-mer duplexes. The dependence of RL on the phasing of the bends as a function of the helical repeat, indicate that the bends associated with (+)-trans-anti-[BP]-N2-dG lesions are relatively rigid in the d(...CG*C...).d(...GCG...) sequences, and flexible in the d(...TG*T...).d(...ACA...) sequence context. These differences are attributed to the orientations of the pyrenyl residues on the 5'-side of the modified deoxyguanosine residues in the minor groove and to the intrinsic roll and tilt characteristics of DNA dinucleotide steps CG, GC, TG, and GT. The influence of flanking bases on the extent and character of DNA bending suggest that base sequence effects may be important in the cellular processing of (+)-trans-anti-[BP]-N2-dG lesions.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1998

Novel mutations in the p16/CDKN2A binding region of the cyclin-dependent kinase-4 gene.

Mutations in genes that lie in the retinoblastoma pathway have been implicated in the pathogenesis of many tumor types. Two critical components that determine progression from G1 to S include p16/CDKN2A and CDK4. Alterations in p16/CDKN2A have been well documented in multiple cancers, including melanoma. However, changes in CDK4 are apparently more rare. Only two alterations, both at codon 24, have been identified in CDK4: an activating arginine-to-cysteine transition and a germ-line arginine-to-histidine substitution in one French kindred. In a survey of 20 neuroblastomas, 17 uncultured metastatic melanomas, 33 uncultured primary uveal melanomas, 8 colon cancer cell lines, and 20 primary colon cancer samples, we found no evidence of mutations in exon 2 of CDK4. From our cell lines derived from metastatic melanomas, we detected two alterations in the functionally critical exon 2 of CDK4: a lysine-to-glutamine transition at codon 22 and the arginine-to-histidine mutation at codon 24. These findings document several novel changes in the p16-binding region of CDK4.

Binding Sites↗
PubMed1998

An estimate of the annual direct cost of treating cutaneous melanoma.

BACKGROUND: Although the survival benefits of early stage melanoma have been clearly documented, the potential economic impact of early versus late stage disease has not been assessed. OBJECTIVE: Our purpose was to estimate the annual direct cost of diagnosing and treating melanoma, based on the number of projected cases of melanoma entering each stage in 1997. METHODS: A model was constructed with assumptions derived from the literature and clinical experience at the Massachusetts General Hospital Melanoma Center and the Boston University Medical Center. Cost estimates were based on 1997 Boston area Medicare reimbursements. RESULTS: The annual direct cost of treating newly diagnosed melanoma in 1997 was estimated to be $563 million. Stage I and II disease each comprised about 5% of the total cost; stage III and stage IV disease consumed 34% and 55% of the total cost, respectively. About 90% of the total annual direct cost of treating melanoma in 1997 was attributable to less than 20% of patients (those patients with advanced disease, that is, stage III and stage IV). CONCLUSION: In addition to the potential survival advantages, aggressive primary prevention through sun protection and intensive screening to enhance earlier detection should reduce the economic burden of melanoma care.

Biopsy↗
PubMed1998

Failure of Q-switched ruby laser to eradicate atypical-appearing solar lentigo: report of two cases.

Cutaneous lasers, including argon, Q-switched Nd:YAG, Q-switched ruby, Q-switched alexandrite, and short pulsed dye lasers, have been used to treat solar lentigines and other benign melanocytic lesions. However, the effects of these lasers at standard fluences on atypical melanocytic lesions have not been examined. We describe two patients in whom the Q-switched ruby laser failed to successfully treat clinically atypical-appearing solar lentigines. In both, clinically atypical-appearing melanocytic lesions were treated with excellent initial cosmetic results. In the first patient, the pigmentation returned several months after treatment and continued to increase in size and color. A biopsy specimen 30 months after Q-switched ruby laser therapy revealed a lentigo maligna melanoma. In the second patient, the lesion recurred 6 months after Q-switched ruby laser therapy, and a biopsy specimen 1 year after treatment showed an early lentigo maligna. Thus Q-switched ruby lasers and other cutaneous lasers capable of targeting melanin may be inadequate to eliminate lentigo maligna and other atypical melanocytic lesions completely. These cases emphasize the importance of careful clinical assessment before any laser surgery and the need to advise patients to return for evaluation should pigmentation return.

Aged↗