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Biomedical subjects

Julian A Kim

Publications and source records attributed to Julian A Kim.

15 recordsLinked to original sources
PubMed2005

The Fourth International Symposium on the Intraductal Approach to Breast Cancer, Santa Barbara, California, 10-13 March 2005.

Intraductal approaches encompass procedures and technologies that are designed to access and interrogate the ductal-alveolar systems of the human breast, and include nipple aspiration, ductal lavage, random periareolar fine needle aspiration, and ductoscopy. These approaches are being used to collect and analyze fluids and cells to develop methods for breast cancer detection and risk assessment; to introduce imaging technologies to explore the mammary tree for abnormalities; to administer therapeutic and/or preventive agents directly to the breast tissue; and to explore the biology of the normal mammary gland. The latest research findings in these areas, presented at The 4th International Symposium on the Intraductal Approach to Breast Cancer in 2005, are summarized in this report.

Breast Neoplasms↗
PubMed2004

Adoptive immunotherapy of cancer with polyclonal, 108-fold hyperexpanded, CD4+ and CD8+ T cells.

T cell-mediated cancer immunotherapy is dose dependent and optimally requires participation of antigen-specific CD4+ and CD8+ T cells. Here, we isolated tumor-sensitized T cells and activated them in vitro using conditions that led to greater than 108-fold numerical hyperexpansion of either the CD4+ or CD8+ subset while retaining their capacity for in vivo therapeutic efficacy. Murine tumor-draining lymph node (TDLN) cells were segregated to purify the CD62Llow subset, or the CD4+ subset thereof. Cells were then propagated through multiple cycles of anti-CD3 activation with IL-2 + IL-7 for the CD8+ subset, or IL-7 + IL-23 for the CD4+ subset. A broad repertoire of TCR Vbeta families was maintained throughout hyperexpansion, which was similar to the starting population. Adoptive transfer of hyper-expanded CD8+ T cells eliminated established pulmonary metastases, in an immunologically specific fashion without the requirement for adjunct IL-2. Hyper-expanded CD4+ T cells cured established tumors in intracranial or subcutaneous sites that were not susceptible to CD8+ T cells alone. Because accessibility and antigen presentation within metastases varies according to anatomic site, maintenance of a broad repertoire of both CD4+ and CD8+ T effector cells will augment the overall systemic efficacy of adoptive immunotherapy.

Journal Article↗
PubMed2004

Nipple-sparing mastectomy: technique and results of 54 procedures.

HYPOTHESIS: The rationale for removal of the nipple-areolar complex (NAC) during total mastectomy centers on long-standing concerns about possible neoplastic involvement of the NAC and its postoperative viability. Nipple-sparing mastectomy (NSM) combines a skin-sparing mastectomy with preservation of the NAC, intraoperative pathological assessment of the nipple tissue core, and immediate reconstruction, thereby permitting better cosmesis for patients undergoing total mastectomy. Neoplastic involvement of the NAC can be predicted before surgery and assessed during the operation, and sustained postoperative viability of the NAC is likely with appropriate surgical technique. RESULTS: Fifty-four NSMs with immediate reconstruction were attempted among 44 patients. Six NAC core specimens revealed neoplastic involvement on frozen section analysis, resulting in conversion to total mastectomies. Forty-five of the 48 completed NSMs maintained postoperative viability of the NAC; 3 NACs had partial loss. CONCLUSION: Nipple-sparing mastectomy is a reasonable option for carefully screened patients.

Adult↗
PubMed2004

Prospective study of intraoperative mammary ductoscopy in patients undergoing partial mastectomy for breast cancer.

BACKGROUND: The purpose of this study was to critically evaluate the added benefit of intraoperative mammary ductoscopy on margin assessment and identification of occult intraductal pathology in patients undergoing therapeutic partial mastectomy for in-situ and invasive breast carcinoma. METHODS: Eligible patients underwent intraoperative mammary ductoscopy before partial mastectomy. In patients where an intraductal abnormality was identified and the mammary ductoscope was not within the partial mastectomy cavity, an additional ductoscopy-directed margin of tissue was analyzed. RESULTS: Nineteen of 30 (63%) patients yielded nipple aspirate fluid and were able to undergo mammary ductoscopy; an intraductal abnormality was identified in 15 of 19 (79%) patients. Only 1 patient had an occult infiltrating carcinoma, which was outside of the resection cavity and identified by ductoscopy. CONCLUSIONS: Although mammary ductoscopy can identify intraductal abnormalities during partial mastectomy in a significant number of patients, many of these findings may be either benign or within the standard field of resection, thus adding no benefit to the patient.

Breast Neoplasms↗
PubMed2004

CD40 monoclonal antibody activation of antigen-presenting cells improves therapeutic efficacy of tumor-specific T cells.

OBJECTIVE: The goal of this study was to determine whether CD40 ligation of antigen presenting cells (APCs) enhances the anti-tumor effector function of tumor draining lymph node (TDLN) T lymphocytes in an adoptive immunotherapy model. STUDY DESIGN: MCA 205 TDLNs were culture activated both in the presence and absence of a stimulatory anti-CD40 monoclonal antibody (mAb) and effector cell phenotype, cytokine secretion in vitro and therapeutic efficacy in vivo were compared. RESULTS: Anti-CD40 mAb induced upregulation of APC cell surface activation markers that promoted generation of T cells that demonstrated an increase in tumor-specific IFN-gamma secretion and a statistically significant reduction in the number of pulmonary tumors (p< 0.01) after adoptive transfer. CONCLUSION: CD40 ligation of APCs in vitro results in the generation of T cells with enhanced effector function against established pulmonary tumors in vivo. SIGNIFICANCE: These findings have direct implications in the development of effective T cell-based immunotherapy of malignant conditions in human beings.

Animals↗
PubMed2004

CDR3 spectratyping identifies clonal expansion within T-cell subpopulations that demonstrate therapeutic antitumor activity.

BACKGROUND: Antigen-specific T cells undergoing clonal expansion share common rearrangements of the variable complementary determining region 3 (CDR3) of the T-cell receptor (TCR), which can be identified using polymerase chain reaction-based V beta (VB) spectratyping. The purpose of this study was to determine whether CDR3 spectratyping identifies clonal expansion within tumor-draining lymph node (TDLN) subpopulations with antitumor therapeutic activity. METHODS: Recently sensitized T cells from 4T1 murine mammary carcinoma TDLN were fractionated based on CD62L (L-selectin) surface expression before RNA isolation and culture. L-selectinlow and L-selectinhigh TDLN were analyzed for T-cell receptor usage by immunophenotyping and CDR3 spectratyping, and then culture activated with anti-CD3/IL-2 to assess therapeutic efficacy after adoptive transfer. RESULTS: Adoptive transfer experiments confirmed that mice treated with culture-activated L-selectinlow TDLN cells exhibited delayed subcutaneous tumor growth and prolonged survival as compared to control or L-selectinhigh-treated mice (P < .01). CDR3 spectratyping demonstrated oligoclonal skewing of the CDR3 regions within several VB families including VB3, VB5.2, and VB17 in L-selectinlow but not in L-selectinhigh TDLN. Although fluorescence-activated cell sorter analysis demonstrated the highest percentage of cells expressing VB13 usage in both populations, CDR3 spectratyping did not identify the presence of clonal expansion. CONCLUSIONS: These data suggest that CDR3 spectratyping may be useful in identifying T cells undergoing clonal expansion that demonstrate antitumor therapeutic activity.

Animals↗
PubMed2003

Targeted therapies for the treatment of cancer.

BACKGROUND: In contrast to conventional cytotoxic chemotherapy and radiation therapy, a new method of targeted cancer therapeutics is being directed towards molecular pathways that underlie the malignant phenotype. These therapies target specific tumor cell receptors or signaling events that are critical to tumor progression while reducing toxicity to normal cells. DATA SOURCES: The purpose of this review is to highlight several examples of novel targeted therapeutics that are currently approved by the FDA for treatment of patients with cancer. Rituxan is a humanized monoclonal antibody that binds to the CD20 antigen present on B cell lymphomas and is currently approved for the treatment of patients with relapsed or refractory low-grade CD20 positive follicular lymphoma. The humanized anti-HER-2/neu herceptin is approved for use in patients with metastatic breast cancer that demonstrates overexpression of HER-2/neu. Finally, Gleevec is a tyrosine kinase inhibitor that inhibits abl-specific phosphorylation and is approved for use in select patients with chronic myelogenous leukemia that is refractory to interferon therapy. CONCLUSIONS: The lessons learned from the use of these therapeutics will add to the growing knowledge of mechanistic approaches to the treatment of patients with cancer based upon targeted therapies, and herald a bright future that will improve the lives of patients with cancer.

Antibodies, Monoclonal↗
PubMed2003

Low-risk palpable breast masses removed using a vacuum-assisted hand-held device.

BACKGROUND: This study evaluates the safety, efficacy, and patient acceptance of a vacuum-assisted, hand-held biopsy device (Mammatome) in the percutaneous removal of breast masses using ultrasound guidance. METHODS: A multicenter, nonrandomized study evaluated 216 women with low-risk palpable lesions. Lesions 1.5 to 3.0 cm in size were removed using an 8-gauge probe. Those lesions <1.5 cm were removed with the 11-gauge probe. Follow-up evaluation was performed at 10 days and 6 months after biopsy. RESULTS: A total of 127 patients had biopsies using the 8-gauge probe, and 89 patients had biopsies using the 11-gauge probe. At 6-month follow-up, 98% of the lesions remained nonpalpable, 73% with no ultrasonographically visible evidence of the original lesion. Most complications were mild and anticipated. Most patients (98%) were satisfied with incision appearance, and 92% of patients would recommend the procedure to others. CONCLUSIONS: Percutaneous removal of palpable benign breast masses using the Mammotome system is feasible and safe, and yields high patient satisfaction. The results at 6 months after biopsy demonstrated the effectiveness of benign lesion removal, with correlative clinical data demonstrating lack of palpability and no need for additional procedures. Continuing evaluation of long-term efficacy is ongoing.

Adult↗
PubMed2003

Axillary lymph node metastases in patients with a final diagnosis of ductal carcinoma in situ.

BACKGROUND: Recent studies report the incidence of axillary metastases in patients with ductal carcinoma in-situ (DCIS) approaches 13%. The purpose of this study was to define the incidence of axillary micrometastases in patients with pure DCIS before and after the introduction of sentinel lymph node biopsy. METHODS: Patients with a final diagnosis of DCIS form the basis of this study. Data were entered prospectively into an Institutional Review Board approved Oracle database from January 1997 through July 2002. RESULTS: One hundred and thirty-four patients had lymph nodes evaluated. Ninety-eight percent of patients had no evidence of metastatic disease and 2% were found to have micrometastases. This was consistent in those who had level I or II lymph node sampling or both and those who had lymphatic mapping and a sentinel lymph node biopsy procedure. CONCLUSIONS: These data do not support axillary lymph node removal of any type in patients with pure DCIS.

Axilla↗
PubMed2003

Does ultrasound core breast biopsy predict histologic finding on excisional biopsy?

BACKGROUND: The purpose of this study was to determine whether ultrasound-guided core breast biopsy accurately predicts the histologic finding of a subsequent excisional procedure. METHODS: Data were collected prospectively from 1997 to 2001 for 832 ultrasound-guided core breast biopsies (USB) that were followed by excisional breast procedure (EP) within 1 year at our institution. The principal histologic finding obtained at USB and EP was identified for each procedure and the degree of agreement was assessed. RESULTS: The USB histology predicted EP histology in 90% (n = 746) of the procedures. The USB histology was more significant than EP histology in 3% (n = 22) of procedures; USB histology underdetermined EP histology in 7% (n = 64) of procedures. Overall, our results indicate moderate agreement between the principal histology identified at USB relative to that identified at EP. CONCLUSIONS: Ultrasound-guided core breast biopsy is an effective diagnostic method, but sampling limitations do exist.

Biopsy↗
PubMed2003

Does core needle breast biopsy accurately reflect breast pathology?

BACKGROUND: Core needle breast biopsy (CB) has replaced excisional biopsy as the initial diagnostic biopsy procedure for many suspicious breast lesions; however, CB remains a sampling procedure. The purpose of this study was to determine the degree of agreement between histology obtained at CB and that obtained at a subsequent excisional procedure (EP). We hypothesized a high degree of agreement. METHODS: Data were collected prospectively for 3035 CBs performed by breast radiologists using either ultrasound or stereotactic guidance between January 1995 and July 2002, 1410 (46%) of which had a subsequent EP within 1 year. Histologic categories were defined as invasive breast cancer, duct carcinoma in-situ, atypia/lobular carcinoma in-situ, and benign. The principal histology (PH) from CB and EP was identified and compared. RESULTS: Overall, there was moderate agreement (kappa=0.669) between CB and EP histology. Complete agreement occurred in 1168 (83%) procedures. For the remaining 242, the PH was identified only at CB for 78 (5%) procedures, and only after EP for 164 (12%) procedures. CONCLUSIONS: Although the majority (83%) of CB and EP demonstrated exact histologic agreement, CB was diagnostic for 1246 (88%) procedures.

Biopsy↗
PubMed2002

Percutaneous removal of benign breast masses using a vacuum-assisted hand-held device with ultrasound guidance.

BACKGROUND: This study evaluates the safety, efficacy, and patient acceptance of a vacuum-assisted, hand-held biopsy device (Mammotome) in percutaneous removal of breast masses using ultrasound guidance. METHODS: A multicenter, nonrandomized study evaluated 124 women with low-risk palpable lesions. Lesions 1.5 cm but <or=3.0 cm were removed using 1-gauge or 8-gauge probes, respectively. Follow-up evaluation was performed at 10 days postbiopsy. RESULTS: The 8-guage probe was used to obtain biopsies from 75 patients, and the 11-gauge was used for 49 patients. Complete removal of the imaged lesion was similar between groups (99% 8-gauge versus 96% 11-gauge). Most complications were mild and anticipated. Most patients (97%) were satisfied with incision appearance, and 98% of patients would recommend the procedure to others. CONCLUSIONS: Percutaneous removal of palpable benign breast masses using the Mammotome system is feasible, safe, and yields high patient satisfaction. Long-term efficacy is being evaluated in the ongoing study.

Adolescent↗
PubMed2002

Directed duct excision by using mammary ductoscopy in patients with pathologic nipple discharge.

BACKGROUND: Duct excision for pathologic nipple discharge (PND) often requires "blind" surgical resection. Intraoperative mammary ductoscopy can allow for direct visualization of intraductal abnormalities during surgical resection. METHODS: We reviewed our experience with 119 patients with PND undergoing ductoscopy-directed duct excision. The variables that could interfere with a successful procedure were analyzed. RESULTS: Cannulation of the discharging duct was successful in 105 of 119 (88%) of patients, and ductoscopy-directed duct excision could be performed in 104 of 119 (87%). A preoperative ductogram was obtained in 70 patients and was positive in 53 of 70 (76%). In this same group, ductoscopy was positive in 63 of 70 (90%). The pathologic diagnoses were as follows: cancer (5), papilloma (84), and hyperplasia (16), for an abnormal pathology yield of 88%. Hyperplasia and cancer were significant predictors of unsuccessful cannulation. In 22 patients, ductoscopy visualized multiple lesions or abnormalities beyond 4 cm. CONCLUSIONS: Mammary ductoscopy for PND is a safe, effective procedure that offers advantages of a high lesion localization rate and intraoperative guidance, therefore negating the need for a preoperative ductogram. Lesions deep within the ductal system can be identified and removed, which would likely have been missed by blind duct excision.

Adolescent↗
PubMedDate not supplied

Race is a fundamental prognostic indicator for 2325 northeastern Ohio women with infiltrating breast cancer.

The goal of this research was to determine if race, independent of socioeconomic status, is a prognostic indicator for women diagnosed with infiltrating breast cancer. We hypothesized that black patients would present with breast cancers having less favorable prognostic indicators relative to white patients, regardless of socioeconomic status. Using data collected prospectively in our institutional review board approved breast center patient registry and 2000 Census Tract data for northeastern Ohio, we compared tumor size, node status, hormone receptor status, clinical outcomes, and socioeconomic status for patients who were self-described as either black or white and who had been diagnosed with infiltrating breast cancer. The chi-square test, t-test, log-rank test, and Cox proportional hazards analysis were used to analyze the data. Kaplan-Meier outcome curves were generated. Data were available for 2325 women, including 313 who were black and 2012 who were white. Compared to white patients, black patients were more likely to have positive axillary nodes and to have hormone receptor-negative tumors. Black patients were also more likely to have positive axillary nodes associated with smaller tumors. Independent of socioeconomic status, black patients were more likely to have poorer overall survival and disease-free survival rates for breast cancer relative to white patients. The prognostic significance of race was not dependent on a concomitant relationship with socioeconomic status.

Black or African American↗