LINE-1 hypomethylation status of circulating cell-free DNA in plasma as a biomarker for colorectal cancer.

Colorectal cancer (CRC) is a serious public health problem and non-invasive biomarkers improving diagnosis or therapy are strongly required. Circulating cell-free DNA (cfDNA) has been a promising target for this purpose. In this study, we evaluated the potential of long interspersed nuclear element-1 (LINE-1) hypomethylation as a blood biomarker for CRC.

Skin-sparing mastectomy. specialty bias and worldwide lack of consensus.

Background: Skin-sparing mastectomy (SSM) is a variation of modified radical mastectomy (MRM) optimized for reconstruction. The authors attempted to determine SSM attitudes and biases within different specialties and countries throughout the world.

Methods: The authors polled 11,485 individuals via e-mail, including members of surgical, medical, and breast oncology societies, about SSM.

Detection of metastases in sentinel lymph nodes of breast cancer patients by multiple-marker RT-PCR.

This study was undertaken to assess a multiple-marker RT-PCR and Southern blot assay for detection of metastases in frozen sections of sentinel lymph nodes from breast cancer patients. Sentinel lymphadenectomy was performed in 41 AJCC (American Joint Committee on Cancer) stage I-IIIA breast cancer patients and 57 sentinel nodes (SNs) were excised. The SN, which is the first node in the lymphatic basin to receive metastases from the primary tumor, was identified using isosulfan blue dye.

Endothelial-selectin ligands sialyl Lewis(x) and sialyl Lewis(a) are differentiation antigens immunogenic in human melanoma.

Background: Sialyl Lewis(x) (sLe(x)) and sialyl Lewis(a) (sLe(a)), the endothelial-selectin ligands involved in extravasation of neutrophils and carcinomas, have been identified in human melanoma. This study explored the following issue: If these ligands are immunogenic tumor-differentiation antigens, they would be potential targets for immunotherapy because of their putative roles in extravasation and metastasis.

Methods: Using a cell-suspension enzyme-linked immunosorbent assay (ELISA), the expression of sLe(x) and sLe(a) on the surface of normal melanocytes, melanoma cells from biopsies, and cell lines (M10-v, M24, and M101) constituting melanoma cell vaccine (MCV) were quantitated.

Melanoma-associated antigens as messenger RNA detection markers for melanoma.

Melanoma is heterogeneous for its biological properties and melanoma-associated antigens (MAAs). This diversity is partially observed in the expression of the MAAs involved with the melanin synthesis pathway. We therefore developed a sensitive multimarker reverse transcription-PCR plus Southern blot assay using five MAAs as molecular markers to detect primary and metastatic melanoma cells.

Tamoxifen activates cellular phospholipase C and D and elicits protein kinase C translocation.

The antiestrogen tamoxifen is widely used for endocrine therapy of breast cancer; however, the mechanisms of estrogen receptor-independent interactions of tamoxifen remain ill defined. Here we examine the effect of tamoxifen on the initial steps of cell signal transduction. To this end, phospholipid metabolism and protein kinase C (PKC) translocation were assessed in CCD986SK human mammary fibroblasts treated with tamoxifen.

The role of lymphoscintigraphy and sentinel node mapping in assessing patient risk in melanoma.

The presence or absence of regional nodal metastases is one of the most important prognostic factors for the survival of patients with primary cutaneous melanoma. The successful outcome of treatment is thus critically dependent on accurate staging of the primary tumor and detection of any occult micrometastases in the regional lymph nodes draining that tumor. Preoperative cutaneous lymphoscintigraphy to identify and visualize the lymphatic drainage patterns from primary tumors and intraoperative lymphatic mapping to identify the first ("sentinel") lymph node in direct communication with the primary tumor are valuable diagnostic tools.

Agents that reverse multidrug resistance, tamoxifen, verapamil, and cyclosporin A, block glycosphingolipid metabolism by inhibiting ceramide glycosylation in human cancer cells.

We have previously shown that multidrug-resistant cancer cells display elevated levels of glucosylceramide (Lavie, Y., Cao, H., Bursten, S.

Current status of human melanoma vaccines: can they control malignant melanoma?

The characterisation of human melanomas as immunogenic and the observation of spontaneous regression have led to the development of active specific immunotherapy in the form of vaccines for treatment of malignant melanoma. These vaccines have recently been the subject of considerable interest, particularly since the introduction of melanoma antigen cloning, the identification of specific peptide sequences recognised by the immune system, and better understanding of antigen presentation. Today, melanoma vaccines are a significant therapeutic agent in treatment of malignant melanoma.

Metastasis of primary melanoma to two separate lymph node basins: prognostic significance.

Background And Methods: Depending on the location of the primary lesion, melanoma patients may develop metastases in more than one regional lymph node basin. To determine whether this is prognostically significant, we reviewed our experience with melanoma patients who had undergone regional lymphadenectomy (RLND) in two separate basins.

Results: Of 3,603 patients who underwent RLND between April 1971 and January 1993, 406 underwent procedures in two separate basins; of these, 120 (30%) had metastases in both basins and 124 (30%) had metastases in one basin.

Detection of metastatic breast cancer by beta-hCG polymerase chain reaction.

Reverse transcriptase-polymerase chain reaction (RT-PCR) for detection of occult malignancies in breast cancer patients is evolving as a useful diagnostic tool. However, no reliable molecular mRNA markers are available. We developed an RT-PCR plus Southern blot assay using beta-hCG (beta-subunit of human chorionic gonadotropin) gene expression as a tumor marker for detection of breast malignancies metastatic to tumor-draining lymph nodes and blood.

Quantitation of the density of cell surface carbohydrate antigens on cancer cells with a sensitive cell-suspension ELISA.

The density of carbohydrate epitopes on the surface of tumor cells is a governing factor for immune recognition and antibody-mediated targeting of tumor-associated carbohydrate antigens in cancer immunotherapy. A sensitive cell-suspension ELISA (cs-ELISA) is developed for quantitation of the functionally exposed carbohydrate epitopes on the cell surface. The factors affecting the measurement of tumor-cell surface glycoconjugates are evaluated using three human melanoma cell lines before and after exposure to various cell preservation treatments.

Tamoxifen retards glycosphingolipid metabolism in human cancer cells.

In this study we provide evidence that tamoxifen, the widely used breast cancer drug, is a potent antagonist of glycolipid metabolism. When added to the medium of cultured multidrug resistant (MDR) KB-V-1 carcinoma cells, tamoxifen, at 5.0 microM, drastically lowered the levels of glucosylceramide (glc-cer), as evidenced by a reduction in glc-cer mass.

Paget's disease of bone possible viral basis.

In 1974, the first report of the presence of viral-like inclusions in the osteoclasts of patients with Paget's disease appeared (Rebel et al 1974). This observation, first made in France, was followed by confirmatory reports from North America, Europe, and Asia. Although no more compelling hypothesis than a viral etiology has been proposed subsequently, definitive proof of viral etiology is still lacking.

Immune response to polyvalent melanoma cell vaccine in AJCC stage III melanoma: an immunologic survival model.

Background: Our polyvalent, allogeneic melanoma cell vaccine (MCV) induces immunoglobulin M (IgM) and immunoglobulin G (IgG) class antibodies to a 90-kDa glycoprotein melanoma-associated antigen (MAA). Additionally, MCV induces delayed-type hypersensitivity (DTH) responses that we previously correlated with survival. We hypothesized that early DTH responses to MCV and early humoral responses to the 90-kDa MAA expressed on MCV cells may be predictive of overall survival.

Incidence and predictors of axillary metastasis in T1 carcinoma of the breast.

Background: The relatively low incidence (6 to 31 percent) of axillary metastasis in patients with T1 carcinoma of the breast (20 mm or smaller) has led some surgeons to question routine axillary lymphadenectomy (ALND) for patients with no palpable axillary metastases and T1 tumors. This study was undertaken to determine the incidence and predictors of axillary lymph node metastasis in patients with T1 carcinoma of the breast and evaluate the role of sentinel lymphadenectomy (SLND) in this context.

Study Design: All patients with T1 invasive carcinoma of the breast treated at the John Wayne Cancer Institute between January 1988 and June 1994 were prospectively studied.

Accumulation of glucosylceramides in multidrug-resistant cancer cells.

Multidrug-resistant (MDR) tumors and cancer cell lines demonstrate a wide variety of biochemical changes. In this study we used drug-sensitive wild-type (wt) cancer cell lines and respective MDR subclones, and we demonstrate the accumulation of distinct lipids in MDR cells. These lipids were either absent or present at very low levels in drug-sensitive cells.

Feasibility of breast-conserving therapy for younger women with breast cancer.

Objective: To determine if breast-conserving therapy (BCT) consisting of segmentectomy, axillary lymph node dissection, and postoperative irradiation is a feasible approach to breast cancer in younger women, whose breast tissue is dense and whose tumors can be difficult to detect and successfully excise.

Design And Patients: We studied BCT in 59 women 35 years old or younger (mean age, 31.7 years) treated for breast cancer since 1982.

Nonpalpable versus palpable invasive breast tumors treated with breast-conserving surgical management.

Most mammographically detected breast cancers are small, nonpalpable malignancies that should be amenable to cure by definitive breast-conserving therapy (BCT) consisting of tumor excision and postoperative radiation. We examined this hypothesis by retrospectively comparing the incidence of local recurrence and the rate of survival in breast cancer patients undergoing BCT for nonpalpable versus palpable lesions. Between 1982 and 1991, 345 patients at the John Wayne Cancer Institute, a large referral center for breast diseases, underwent BCT for invasive ductal and/or invasive lobular breast carcinomas: 120 (35%) had nonpalpable lesions detected by mammography (MG group), and 225 (65%) had palpable lesions detected by physical exam (PE group).

Nipple-areolar preservation during breast-conserving therapy for subareolar breast carcinomas.

Objective: To determine if women with subareolar breast carcinoma can be successfully treated by breast-conserving therapy consisting of segmental mastectomy that preserves the nipple-areolar complex, axillary lymph node dissection, and postoperative irradiation.

Design: Prospective study.

Setting: Tertiary care cancer center.

Percutaneous core biopsy of the breast: effect of operator experience and number of samples on diagnostic accuracy.

Objective: The purpose of our study was to assess the degree of operator experience and the number of core biopsy samples required to achieve an accurate histologic diagnosis for each of five common mammographically defined lesions, using percutaneous core breast biopsy performed on a dedicated prone biopsy table.

Subjects And Methods: A prospective multisite study was performed that involved nine institutions (academic and private) with experienced breast radiologists and the use of dedicated prone biopsy table units with digital assistance and standardized protocol. Asymptomatic women evaluated during a 2-year study period were assigned a mammographic diagnosis reported in a manner prescribed by the American College of Radiology Breast Imaging Reporting and Data System lexicon.

Desmoid tumor occurring after reconstruction mammaplasty for breast carcinoma.

We present a case of desmoid tumor associated with prior alloplastic breast reconstruction. Wide local excision that includes chest wall resection, if necessary, is the primary treatment of choice. Patients with extensive nonresectable or recurrent disease may benefit from radiation therapy.

Current management of ductal carcinoma in situ.

Ductal carcinoma in situ represents a biologically and histologically heterogeneous group of lesions characterized by the proliferation of neoplastic epithelial cells confined to the ducts of the breast. Before screening mammography, ductal carcinoma in situ was considered uncommon; patients were usually diagnosed by a breast mass or bloody nipple discharge, and their treatment was mastectomy. Today it represents 20% to 30% of mammographically detected breast cancers and 10% to 15% of all diagnosed breast cancers in the United States.

Prognostic factors in 1,521 melanoma patients with distant metastases.

Background: Although over 7,000 people die from malignant melanoma each year, there are limited prognostic data for patients with metastatic disease. A retrospective analysis was undertaken to identify variables that accurately predict outcome and to determine if the survival rate of patients with melanoma treated for distant metastases (American Joint Committee on Cancer [AJCC] stage IV disease) at the authors' institution changed between 1971 and 1993.

Study Design: Data for 1,521 patients with AJCC stage IV melanoma treated by the staff of the John Wayne Cancer Institute were reviewed, and a univariate and multivariate survival analysis against ten clinical and pathological variables was performed using the Cox proportional hazard regression model.