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Christina J Kim

Publications and source records attributed to Christina J Kim.

8 recordsLinked to original sources
PubMed2005

Epigenetic silencing of DSC3 is a common event in human breast cancer.

INTRODUCTION: Desmocollin 3 (DSC3) is a member of the cadherin superfamily of calcium-dependent cell adhesion molecules and a principle component of desmosomes. Desmosomal proteins such as DSC3 are integral to the maintenance of tissue architecture and the loss of these components leads to a lack of adhesion and a gain of cellular mobility. DSC3 expression is down-regulated in breast cancer cell lines and primary breast tumors; however, the loss of DSC3 is not due to gene deletion or gross rearrangement of the gene. In this study, we examined the prevalence of epigenetic silencing of DSC3 gene expression in primary breast tumor specimens. METHODS: We used bisulfite genomic sequencing to analyze the methylation state of the DSC3 promoter region from 32 primary breast tumor specimens. We also used a quantitative real-time RT-PCR approach, and analyzed all breast tumor specimens for DSC3 expression. Finally, in addition to bisulfite sequencing and RT-PCR, we used an in vivo nuclease accessibility assay to determine the chromatin architecture of the CpG island region from DSC3-negative breast cancer cells lines. RESULTS: DSC3 expression was downregulated in 23 of 32 (72%) breast cancer specimens comprising: 22 invasive ductal carcinomas, 7 invasive lobular breast carcinomas, 2 invasive ductal carcinomas that metastasized to the lymph node, and a mucoid ductal carcinoma. Of the 23 specimens showing a loss of DSC3 expression, 13 (56%) were associated with cytosine hypermethylation of the promoter region. Furthermore, DSC3 expression is limited to cells of epithelial origin and its expression of mRNA and protein is lost in a high proportion of breast tumor cell lines (79%). Lastly, DNA hypermethylation of the DSC3 promoter is highly correlated with a closed chromatin structure. CONCLUSION: These results indicate that the loss of DSC3 expression is a common event in primary breast tumor specimens, and that DSC3 gene silencing in breast tumors is frequently linked to aberrant cytosine methylation and concomitant changes in chromatin structure.

Breast Neoplasms↗
PubMed2002

Effects of interleukin 2 therapy on lymphocyte magnesium levels.

Interleukin 2 (IL-2) can cause partial or complete tumor regression in approximately 20% of patients with renal cell carcinoma. Among the many physiologic effects of IL-2, decreased serum levels of the divalent cations magnesium (Mg) and calcium have been demonstrated, with corresponding decreases in their urinary excretion. We investigated the effect of IL-2 on lymphocyte Mg levels among patients receiving three different dosing regimens. Twenty-eight patients with metastatic renal cell carcinoma were treated with high-dose intravenous, low-dose intravenous, or subcutaneous IL-2 therapy. Serum ionized Mg, urinary Mg, and peripheral blood mononuclear cell Mg levels were measured in samples from patients during treatment and compared with pretreatment levels. Serum Mg and ionized Mg levels decreased for all patients within 12 hours of treatment (P <.005) and remained low for the duration of therapy. Urinary Mg decreased in parallel with serum levels in all patients (P <.005). The peripheral blood mononuclear cell Mg content per cell increased within 24 hours of treatment (P <.005). The magnitude of these changes was similar during the first week of treatment for patients receiving intravenous or subcutaneous administration of IL-2. During IL-2 therapy, lymphocyte Mg increases coincident with serum Mg depletion. Mg availability may have functional implications for lymphocyte proliferation and integrin function.

Adult↗
PubMedDate not supplied

The new melanoma staging system.

BACKGROUND: Classification schemas for cancers are useful for predicting overall survival and selecting patients for treatment. Historically, the most important factors in determining prognosis in patients with melanoma have been tumor thickness and lymph node status. Sentinel lymph node mapping defines a subset of patients with microscopic metastatic disease can be identified, offering greater accuracy in staging. METHODS: The authors reviewed studies evaluating the prognostic factors that are significant in predicting survival in patients with melanoma. The newly revised American Joint Committee on Cancer (AJCC) staging system for melanoma is compared with the 1997 AJCC staging system currently in use. RESULTS: The changes in the new AJCC melanoma staging system reflect the new prognostic factors that have been found to be important in predicting survival. These include primary tumor thickness (tumor depth in millimeters is more predictive than the level of invasion) and ulceration, number of metastatic lymph nodes, micrometastatic disease based on the sentinel lymph node biopsy technique or elective node dissection, the site(s) of distant metastatic disease and serum LDH levels. CONCLUSIONS: Major revisions have been made to form a new AJCC staging system for melanoma, which will become official in 2002. This system will provide more accurate and precise information regarding patient prognosis. Validation studies are needed to confirm the accuracy of this revised staging system.

Biopsy, Needle↗
PubMedDate not supplied

Immunotherapy for melanoma.

BACKGROUND: Immunotherapy for cancers is based on the principle that the host's immune system is capable of generating immune responses against tumor cells. Currently available treatments for melanoma patients are limited by poor response rates. Interferon-a has been approved for adjuvant treatment of stage III melanoma with improved survival. New and more innovative approaches with improved efficacy are needed. METHODS: We reviewed the various new approaches and strategies for immunotherapy for the treatment of melanoma. RESULTS: Immunotherapy for melanoma includes a number of different strategies with vaccines utilizing whole cell tumors, peptides, cytokine-mediated dendritic cells, DNA and RNA, and antibodies. CONCLUSIONS: A variety of approaches can be used to enhance immune reactivity in patients with melanoma. Preclinical studies and initial clinical trials have shown promising results. Additional clinical trials are currently ongoing to evaluate the clinical efficacy and the associated toxicities of these novel treatment strategies.

Cancer Vaccines↗
PubMedDate not supplied

Metastatic melanoma: chemotherapy to biochemotherapy.

BACKGROUND: Single-agent or combination chemotherapy regimens have not impacted the short median survival of patients with metastatic melanoma, and complete or durable responses are rare. Biologic response modifiers (interferon and interleukin-2) have produced durable remissions in a small cohort of patients, and phase II trials of biochemotherapy suggest more benefit. METHODS: The authors retrospectively reviewed the status of the current treatments of metastatic melanoma focusing on biochemotherapy. RESULTS: Regimens include both sequential and concurrent approaches for inpatient and outpatient treatment settings. Overall response rates in phase II trials are 40% to 60% with complete responses of 10% to 20% and median survivals in the 11- to 12-month range. Modifications of concurrent biochemotherapy regimens have maintained efficacy and reduced toxicity. Small phase III trials suggest a survival advantage of biochemotherapy (P=.05). CONCLUSIONS: Biochemotherapy remains a promising new treatment for metastatic melanoma. A large Intergroup trial E3695 comparing concurrent biochemotherapy to combination chemotherapy alone is powered to answer important survival questions.

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

The promise of microarray technology in melanoma care.

BACKGROUND: Genetic aberration is responsible for the development of neoplastic potential in a number of malignancies. These DNA alterations result in significant changes in gene expression that may now be measured and catalogued. The microarray technique screens and identifies expressed genes that may be responsible for tumorigenesis. METHODS: The authors review the application of the microarray technique in malignant melanoma. RESULTS: Candidate melanoma suppressor genes have been identified in melanoma cell lines using this technique. Furthermore, molecular classification using gene expression profiling may improve the accuracy of the staging system for determining prognosis. CONCLUSIONS: The microarray technique is in its initial development for clinical application in a variety of tumor models. Melanoma is an ideal system to study the genetic changes associated with the stepwise progression of malignancy. It may be possible to efficiently screen the entire human genome to identify the particular aberrations in gene expression responsible for tumorigenesis in melanoma.

Clinical Trials as Topic↗
PubMedDate not supplied

Aberrant methylation of the maspin promoter is an early event in human breast cancer.

The maspin gene functions as a tumor suppressor in human breasts, and its expression is frequently lost during breast cancer progression. In vitro models of human breast cancer indicate that the loss of maspin expression is closely linked to aberrant methylation of the maspin promoter. We conducted a study on 30 archival ductal carcinoma in situ (DCIS) specimens to determine if aberrant methylation of the maspin promoter occurred in vivo, and whether it occurred early in breast cancer evolution. Healthy tissue obtained from reduction mammoplasty was used as normal control. Results from immunohistochemical analysis indicate that maspin expression is lost in a substantial fraction of DCIS specimens (57%). Bisulfite sequencing of DNA isolated from laser capture-microdissected normal and neoplastic ducts showed that loss of maspin expression was often, but not always, linked to aberrant methylation of the maspin promoter, suggesting that other mechanisms, in addition to aberrant methylation, participate and/or cooperate to silence maspin gene expression. Taken together, these results indicate that aberrant methylation of the maspin promoter is an early event in human breast cancer.

Base Sequence↗