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E Levine

Publications and source records attributed to E Levine.

At least 37 records · Page 2Linked to original sources
PubMed2000

Relationship between in vitro chromosomal radiosensitivity of peripheral blood lymphocytes and the expression of normal tissue damage following radiotherapy for breast cancer.

BACKGROUND AND PURPOSE: There is a need for rapid and reliable tests for the prediction of normal tissue responses to radiotherapy, as this could lead to individualization of patient radiotherapy schedules and thus improvements in the therapeutic ratio. Because the use of cultured fibroblasts is too slow to be practicable in a clinical setting, we evaluated the predictive role of assays of lymphocyte chromosomal radiosensitivity in patients having radiotherapy for breast cancer. MATERIALS AND METHODS: Radiosensitivity was assessed using a micronucleus (MN) assay at high dose rate (HDR) and low dose rate (LDR) on lymphocytes irradiated in the G(0) phase of the cell cycle (Scott D, Barber JB, Levine EL, Burril W, Roberts SA. Radiation-induced micronucleus induction in lymphocytes identifies a frequency of radiosensitive cases among breast cancer patients: a test for predispostion? Br. J. Cancer 1998;77;614-620) and an assay of G(2) phase chromatid radiosensitivity ('G(2) assay') (Scott D, Spreadborough A, Levine E, Roberts SA. Genetic predisposition in breast cancer. Lancet 1994; 344: 1444). In a study of acute reactions, blood samples were taken from breast cancer patients before the start of radiotherapy, and the skin reaction documented. 116 patients were tested with the HDR MN assay, 73 with the LDR MN assay and 123 with the G(2) assay. In a study of late reactions, samples were taken from a series of breast cancer patients 8-14 years after radiotherapy and the patients assessed for the severity of late effects according to the'LENT SOMA' scales. 47 were tested with the HDR assay, 26 with the LDR assay and 19 with the G(2) assay. For each clinical endpoint, patients were classified as being normal reactors or 'highly radiosensitive patients' (HR patients (Burnet NG. Johansen J, Turesson I, Nyman J. Describing patients' normal tissue reactions: Concerning the possiblity of individualising radiotherapy dose presciptions based on potential predictive assays of normal tissue radiosensitivity. Int. J. Cancer 1998;79:606-613)). RESULTS: The HR patients could be identified in some of the assays. For example, for acute skin reactions, 9/123 patients were judged as HR; they had significantly higher G(2) scores than normal reactors (P=0.004). For the late reactions, the mean HDR MN scores were higher for the 4/47 patients who had severe telangiectasia (P=0.042) and the 8/47 patients had severe fibrosis (P=0.055). However, there were no trends towards increased chromosomal radiosensitivity with the micronucleus scores at HDR or LDR, or with G(2) chromosomal radiosensitivity. CONCLUSIONS: While these results support the concept of using lymphocytes to detect elevated sensitivity to radiotherapy (as an alternative to fibroblasts), these assays are unlikely to be of assistance for the prediction of normal tissue effects in the clinic in their present form.

Adult↗
PubMed2000

October 18, 2000 8:30-8:45. Problem Solving with FDG Positron Emission Mammography.

Purpose: To examine one potential clinical application of dedicated devices for positron emission mammography.Background: Dedicated devices for breast imaging with FDG have technical specifications that appear well-suited for detecting small breast cancers, including registration with x-rays, high count sensitivity, and spatial resolution in the 2-3 mm range.Methods: In IRB-approved clinical trials, patients who were scheduled for biopsy for suspicious findings on x-ray mammograms were injected with 10-20 mCi FDG intravenously one to two hours prior to x-ray guided core biopsy or lumpectomy. Positron emission mammograms using a dedicated device were performed just before biopsy, and results compared to final histopathology.Results: Three patients whose cancers were missed on initial x-ray mammograms or whose mammograms contained subtle abnormalities that were not strongly suspicious for cancer, were shown to have very suspicious hot spots on positron emission mammograms. These patients were later confirmed to have cancer.Discussion: The role for dedicated devices for positron emission mammography is evolving. Finding cancers that are either mammographically occult or have low indices of suspicion is a potential application for this technique. Further clinical and technical work will be needed to better define the strengths and weaknesses of the device in this application.

Journal Article↗
PubMed2000

ATM heterozygosity and breast cancer: screening of 37 breast cancer patients for ATM mutations using a non-isotopic RNase cleavage-based assay.

Based upon the results of several epidemiologic studies, it has been suggested that women who are carriers for a mutation in the ataxia telangiectasia-mutated (ATM) gene are susceptible for the development of breast cancer. Therefore, 37 consecutive breast cancer patients were screened for the presence of a germline ATM mutation using a non-isotopic RNase cleavage-based assay (NIRCA). This paper reports the first use of NIRCA for detection of ATM mutations in breast cancer patients. Using this assay, no ATM mutations were found in our patient population. This result is similar to the findings of other studies that have employed approaches complementary to NIRCA.

Adult↗
PubMed2000

Obstetric outcomes in 102 pregnancies after preimplantation genetic diagnosis.

OBJECTIVE: We sought to determine whether preimplantation genetic diagnosis is associated with particular pregnancy or delivery complications. STUDY DESIGN: A total of 102 consecutive pregnancies after preimplantation genetic diagnosis by polar body removal performed at Illinois Masonic Medical Center resulting in 114 live births were analyzed. All patients were given a delivery and newborn questionnaire, and attempts were made to contact and question them regarding any pregnancy complications and type of delivery. Permission was obtained to examine medical records and discuss the patient's pregnancy with her obstetrician when questions existed with respect to complications or indication for cesarean delivery. RESULTS: Delivery and newborn questionnaires were completed or telephone contact was achieved for 100 of the 102 pregnancies. There were 85 singleton, 9 twin, and 7 triplet pregnancies. Of the 7 triplet gestations, 3 couples elected multifetal pregnancy reduction to twins and healthy triplets were born to 4 couples between 32 and 36 weeks by cesarean delivery. Of the 80 singleton deliveries, 60 (75%) progressed to term. Of these 60 term singleton deliveries, 34 were vaginal, 23 were cesarean (40%), and 3 delivery types were unknown. The incidence of small-for-gestational-age infants was 3% for neonates in the 60 term singleton deliveries and 7% in the entire cohort of 80 singleton deliveries. Only 3 pregnancy complications (other than premature delivery) were reported more than once. There were 3 instances each of gestational diabetes, intrauterine growth restriction, and pregnancy-induced hypertension. There was 1 case each of HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome, congestive heart failure, mild oligohydramnios, and abruptio placentae. The indications for cesarean delivery were (in descending order) failure of labor to progress (n = 7), fetal distress (n = 4), placenta previa (n = 4), elective repeat cesarean delivery (n = 4), triplets (n = 3), uterine scarring (n = 3), 1 twin in the breech position (n = 3), failed forceps delivery (n = 2), and a variety of other indications that occurred in only 1 patient each. All preimplantation genetic diagnoses were confirmed by prenatal or postnatal testing. No diagnostic errors were made in this cohort of patients or in any patients undergoing preimplantation genetic diagnosis having polar body removal in our center. CONCLUSIONS: Preimplantation genetic diagnosis is associated with a risk of multiple gestations, cesarean delivery, and placenta previa. Cesarean delivery rates and multiple gestation rates are comparable to those of patients undergoing in vitro fertilization in general. The preimplantation genetic diagnosis itself does not seem to cause an increased risk for any particular pregnancy complication, with the possible exception of placenta previa, which was seen in 4% of patients.

Cesarean Section↗
PubMed2000

Role of neurotropins in rat embryonic testis morphogenesis (cord formation).

The process of seminiferous cord formation is the first morphological event that differentiates a testis from an ovary and indicates male sex determination. Cord formation occurs by embryonic Day 14 (Day 0 = plug date; E14) in the rat. A series of experiments were conducted to determine if neurotropins and their receptors are important for the process of rat embryonic cord formation. The expression of low affinity neurotropin receptor (p75/LNGFR) was determined by immunohistochemistry on sections of both testis and ovary from E13 through birth (Day 0, P0) with an antibody to p75/LNGFR. The staining for p75/LNGFR was present in the mesonephros of E13 gonads and in a sex-specific manner appeared around developing cords at E14 in the embryonic testis. At birth, staining for p75/LNGFR was localized to a single layer of cells (i.e., peritubular cells) that surrounded the seminiferous cords. The genes for both neurotropin 3 (NT3) and for corresponding high affinity neurotropin trkC receptor were found to be expressed in the E14 rat testis, as well as other neurotropins and receptors. Immunocytochemical analysis of E14 rat testis demonstrated that NT3 was localized to the Sertoli cells and trkC was present in individual cells of the interstitium at E16 and in selected preperitubular cells at E18. Previously, the peritubular cells adjacent to the cords were demonstrated to be derived from migrating mesonephros cells around the time of cord formation. To determine if neurotropins were involved in cord formation, the actions of neurotropins were inhibited. A high affinity neurotropin receptor (trk)-specific kinase inhibitor, K252a, was used to treat organ cultures of testes from E13 rats prior to cord formation. Treatment of E13 testis organ cultures with K252a completely inhibited cord formation. K252a-treated organ cultures of E14 testis that contained cords did not alter cord morphology. A second experiment to inhibit neurotropin actions utilized a specific antagonist trk-IgG chimeric fusion protein and E13 testis organ cultures. The trk-IgG molecules dimerize with endogenous trk receptors and inhibit receptor signaling and activation of ligand function. Forty percent of E13 testis organ cultures treated with trkC-IgG had significantly reduced cord formation. TrkA-IgG had no effect on initiation of cords; however, in fifty percent of the treated organs, a "swollen" appearance of the cord structures was observed. Experiments using trkB-IgG chimeric protein on E13 organ cultures had no effect on cord formation or cord morphology. The testes from trkC and NT3 knockout mice were examined to determine if there were any morphological differences in the testis. NT3 knockouts appeared to have normal cord morphology in E15 and E17 testis. TrkC knockout mice also had normal cord morphology in E14 and P0 testis. Both NT3 and trkC knockout-mice testis had less interstitial area than wild-type controls. In addition, the trkC knockout mice have an increased number of cells expressing p75LNGFR within the cords when compared to controls or NT3 knockout mice. Combined observations suggest compensation between the different neurotropin ligands, receptors, and/or possibly different growth factors for this critical biological process. In summary, results suggest a novel nonneuronal role for neurotropins in the process of cord formation during embryonic rat testis development. The hypothesis developed is that neurotropins are involved in the progression of male sex differentiation and are critical for the induction of embryonic testis cord formation.

Animals↗
PubMed2000

Role of transforming growth factor-alpha and the epidermal growth factor receptor in embryonic rat testis development.

Embryonic testis development requires the morphogenesis of cords and growth of all cell populations to allow organ formation. It is anticipated that coordination of the growth and differentiation of various cell types involves locally produced growth factors. The current study was an investigation of the hypothesis that transforming growth factor-alpha (TGF-alpha) is involved in regulating embryonic testis growth. TGF-alpha has previously been shown to function in the postnatal testis. TGF-alpha and other members of the epidermal growth factor (EGF) family act through the epidermal growth factor receptor (EGFR) to stimulate cell proliferation and tissue morphogenesis. To understand the potential actions of TGF-alpha in the embryonic testis, general cell proliferation was investigated. Characterization of cell proliferation in the rat testis throughout embryonic and postnatal development indicated that each cell type has a distinct pattern of proliferation. Germ cell growth was transiently suppressed around birth. Interstitial cell growth was high embryonically and decreased to low levels around birth. A low level of Sertoli cell proliferation was observed at the onset of testis cord formation. Sertoli cell proliferation in early embryonic development was low; the levels were high later in embryonic development and remained high until the onset of puberty. Both TGF-alpha and the EGFR were shown to be expressed in the embryonic and postnatal rat and mouse testis. Perturbation of TGF-alpha function using neutralizing antibodies to TGF-alpha on testis organ cultures dramatically inhibited the growth of both embryonic and neonatal testis. TGF-alpha antibodies had no effect on cord formation. The TGF-alpha antibody was found to be specific for TGF-alpha in Western blots when compared to EGF and heregulin. Testis growth was also inhibited by perturbation of EGFR signaling using an EGFR kinase inhibitor. Therefore, TGF-alpha appears to influence embryonic testis growth but not morphogenesis (i.e., cord formation). Treatment of embryonic testis organ cultures with exogenous TGF-alpha also perturbed development, leading to an increased proliferation of unorganized cells. Testis from EGFR and TGF-alpha knockout mice were analyzed for testis morphology. TGF-alpha knockout mice had no alterations in testis phenotype, while EGFR knockout mice had a transient decrease in the relative amount of interstitial cells before birth. Observations suggest that there may be alternate or compensatory factors that allow testis growth to occur in the apparent absence of TGF-alpha actions in the mutant mice. In summary, the results obtained suggest that TGF-alpha is an important factor in the regulation of embryonic testis growth, but other factors will also be involved in the process.

Animals↗
PubMed2000

Coarsening of a class of driven striped structures

The coarsening process in a class of driven systems exhibiting striped structures is studied. The dynamics is governed by the motion of the driven interfaces between the stripes. When two interfaces meet they coalesce thus giving rise to a coarsening process in which l(t), the average width of a stripe, grows with time. This is a generalization of the reaction-diffusion process A+A-->A to the case of extended coalescing objects, namely, the interfaces. Scaling arguments which relate the coarsening process to the evolution of a single driven interface are given, yielding growth laws for l(t), for both short and long times. We introduce a simple microscopic model for this process. Numerical simulations of the model confirm the scaling picture and growth laws. The results are compared to the case where the stripes are not driven and different growth laws arise.

Journal Article↗
PubMed1999

TGF-beta1 levels in pre-treatment plasma identify breast cancer patients at risk of developing post-radiotherapy fibrosis.

A serious complication of radiotherapy in the treatment of cancer patients is the late onset of fibrosis in normal tissues. Transforming growth factor beta (TGF-beta) is emerging as a key mediator of the fibrotic process through its effects on stimulation of fibroblast proliferation, migration and extracellular matrix (ECM) synthesis. The fact that radiation-induced vascular injury tends to precede the development of fibrosis has led to the suggestion that vascular damage is crucial in its pathogenesis. CD105, the specific type III vascular receptor for TGF-beta1 and -beta3, modulates cell proliferation and ECM production in response to TGF-beta in vitro. In this study, we have quantified the levels of TGF-beta1 and soluble CD105-TGF-beta1 complex in 91 pre-radiotherapy plasma samples from early-stage (T1 or T2) breast cancer patients utilising an enhanced chemiluminescence ELISA system. During the follow-up period, 24 patients had developed moderate and one severe fibrosis of the breast. The mean TGF-beta1 level in these 25 patients was 203.2 +/- 37.3 pg/ml, which was significantly elevated above the level for those with no fibrosis. Furthermore, a significantly lower CD105-TGF-beta1 complex level was observed in the former compared to the latter. Spearman's correlation analysis showed that TGF-beta1 was positively correlated and the CD1O5-TGF-beta1 complex inversely correlated with the occurrence of breast fibrosis. Using a cut-off value of 96 pg/ml, the sensitivity and specificity of TGF-beta1 levels in predicting breast fibrosis were 76% and 74%, respectively. Our results indicate that TGF-beta1 and the receptor-ligand complex appear to be of clinical value in identifying patients at risk of developing post-radiotherapy fibrosis.

Adult↗
PubMed1999

Elevation of serum riboflavin carrier protein in breast cancer.

Presently available tumor markers have had a limited clinical impact. Riboflavin carrier protein (RCP) is an estrogen inducible protein that occupies a key position in riboflavin metabolism. Because other vitamin carrier proteins (VCP) have been shown to be overexpressed in patients with malignant disease, we evaluated serum RCP levels in patients with adenocarcinoma of the breast. In this prospective blinded study, patients with breast cancer, benign breast disease, and healthy controls were analyzed for RCP levels. Using a highly sensitive RIA, we observed that serum RCP levels were significantly elevated in women with breast cancer (n = 52) as compared with control subjects [n = 50; 6.06 +/- 7.27 ng/ml versus 0.70 +/- 0.19 ng/ml (mean +/- SD), respectively; P < 0.0001]. A serum RCP level of > or = 1.0 ng/ml was highly predictive of the presence of breast cancer, detecting 88% of tumors in stages I-II and 100% of tumors in stages III-IV. Overall, this RCP assay has a sensitivity of 92.3%, a specificity of 88%, a positive predictive value of 88.9%, and a negative predictive value of 91.7%. These results show increased serum levels of RCP in breast adenocarcinoma patients and suggest that RCP levels may be useful as a new marker for breast cancer. The positive predictive value in early-stage breast cancer suggests that the RCP assay may be a useful adjunct to present screening technology.

Adenocarcinoma↗
PubMed1998

Role of transforming growth factor beta3 in lymphatic metastasis in breast cancer.

Transforming growth factor-betas (TGFbetas) play a prominent role in tumour growth and metastasis by enhancing angiogenesis and suppressing immune surveillance. Despite the increased interest in the effect of TGFbetas on tumour progression, little is known about the importance of TGFbeta3 and its receptor CD105 in breast cancer. In the present study, we measured the plasma levels of TGFbeta3, CD105-TGFbeta3 complexes and TGFbeta1 in 80 patients with untreated early-stage breast cancer using an enhanced chemiluminescence ELISA method. Of the 80 patients, 14 were histologically confirmed as having axillary lymph node metastases, while the remainder had no evidence of lymph node involvement. The results showed that levels of both TGFbeta3 and CD105-TGFbeta3 complex were significantly elevated in patients with positive lymph nodes compared to those without node metastasis. Furthermore, the levels of both TGFbeta3 and CD105-TGFbeta3 complex correlated with lymph node status. The only patient who died of the disease had very high plasma levels of TGFbeta3 and CD105-TGFbeta3 complex and positive lymph nodes; this patient developed lung metastases within 2 years of diagnosis. No significant correlation was seen between either TGFbeta3 or CD105-TGFbeta3 complex levels and tumour stage, size or histological grade. Plasma TGFbeta1 levels were not correlated with node metastasis, tumour stage, grade or size. Our data suggest that plasma levels of TGFbeta3 and CD105-TGFbeta3 complex may be of prognostic value in the early detection of metastasis of breast cancer.

Adult↗
PubMed1998

Expression of cyclooxygenase-1 and cyclooxygenase-2 in human breast cancer.

BACKGROUND: Numerous studies have demonstrated that the levels of prostaglandins are greater in various cancers, including breast cancer and colon cancer, than in normal tissues. In particular, the inducible form of cyclooxygenase (COX), the rate-limiting enzyme in prostaglandin biosynthesis, is overexpressed in colon tumors. Epidemiologic studies have demonstrated that the use of aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs) can reduce the risk of colon cancer and, to a lesser extent, the risk of breast cancer. NSAIDs are known to inhibit COX, suggesting that the beneficial effect of NSAIDs in colon cancer may be related to COX overexpression in this disease. This possibility led us to ask whether COX is also overexpressed in breast cancers. METHODS: Surgical specimens from 44 patients with breast cancer who had undergone lumpectomy or mastectomy were analyzed by immunoblot analysis and immunohistochemical analysis to determine the expression profile of the constitutively expressed form of cyclooxygenase (COX-1) and the inducible form (COX-2); the specimens from 14 patients included normal breast tissue. RESULTS: Expression of COX-1 protein was substantially higher in 30 of 44 tumor samples than in any of the 14 normal tissue specimens. Immunoblot analysis revealed extremely high levels of COX-2 protein in two tumor samples. Immunohistochemical staining of specimens that expressed COX-1 and/or COX-2 revealed that COX-1 was localized in stromal cells adjacent to the tumor but not in tumor cells. In contrast, COX-2 was localized primarily in tumor cells but also appeared in stromal cells. CONCLUSION: Our results suggest that overexpression of COX may not be unique to colon cancer and may be a feature common to other epithelial tumors.

Breast Neoplasms↗
PubMed1998

Trunk reconstruction with the free vastus lateralis flap.

A case is presented of a massive, full-thickness, trunk-wall defect successfully reconstructed with a free-tissue transfer of the entire vastus lateralis muscle. Indications, technical details, and donor-site considerations are discussed.

Aged↗
PubMed1998

Upstairs downstairs: vertical integration of a pediatric service.

BACKGROUND: The combined effects of recent changes in health care financing and training priorities have compelled academic medical centers to develop innovative structures to maintain service commitments yet conform to health care marketplace demands. In 1992, a municipal hospital in the Bronx, New York, affiliated with a major academic medical center reorganized its pediatric service into a vertically integrated system of four interdependent practice teams that provided comprehensive care in the ambulatory as well as inpatient settings. One of the goals of the new system was to conserve inpatient resources. OBJECTIVE: To describe the development of a new vertically integrated pediatric service at an inner-city municipal hospital and to test whether its adoption was associated with the use of fewer inpatient resources. DESIGN: A descriptive analysis of the rationale, goals, implementation strategies, and structure of the vertically integrated pediatric service combined with a before-and-after comparison of in-hospital resource consumption. METHODS: A before-and-after comparison was conducted for two periods: the period before vertical integration, from January 1989 to December 1991, and the period after the adoption of vertical integration, from July 1992 to December 1994. Four measures of inpatient resource use were compared after adjustment for case mix index: mean certified length of stay per case, mean number of radiologic tests per case, mean number of ancillary tests per case, and mean number of laboratory tests per case. Difference-in-differences-in-differences estimators were used to control for institution-wide trends throughout the time period and regional trends in inpatient pediatric practice occurring across institutions. Results. In 1992, the Department of Pediatrics at the Albert Einstein College of Medicine reorganized the pediatric service at Jacobi Medical Center, one of its principal municipal hospital affiliates, into a vertically integrated pediatric service that combines ambulatory and inpatient activities into four interdependent practice teams composed of attending pediatricians, allied health professionals, house officers, and social workers. The new vertically integrated service was designed to improve continuity of care for patients, provide a model of practice for professional trainees, conserve scarce resources, and create a clinical research infrastructure. The vertically integrated pediatric service augmented the role of attending pediatricians, extended the use of allied health professionals from the ambulatory to the inpatient sites, established interdisciplinary practice teams that unified the care of pediatric patients and their families, and used less inpatient resources. Controlling for trends within the study institution and trends in the practice of pediatrics across institutions throughout the time period, the vertical integration was associated with a decline in 0.6 days per case, the use of 0.62 fewer radiologic tests per case, 0.21 fewer ancillary tests per case, and 2.68 fewer laboratory tests per case. CONCLUSIONS: We conclude that vertical integration of a pediatric service at an inner-city municipal hospital is achievable; conveys advantages of improved continuity of care, enhanced opportunities for primary care training, and increased participation of senior clinicians; and has the potential to conserve significant amounts of inpatient resources.

Academic Medical Centers↗
PubMed1998

AIDS in Staten Island.

Explore the source record for details and available documents.

Acquired Immunodeficiency Syndrome↗
PubMed1998

The first four years of the Uniformed Services University of the Health Sciences Graduate School of Nursing.

The Graduate School of Nursing (GSN) was established at the Uniformed Services University of the Health Sciences in 1993 to prepare advanced practice nurses, namely family nurse practitioners (FNPs) and nurse anesthetists (CRNAs), for the uniformed services. A study of needs for nurses in the uniformed services in these specialties indicated that by the year 2000 there would be a need requiring a total enrollment in educational programs of 268 CRNAs and 100 FNPs over a 5-year period. Offering the master of science in nursing degree, the GSN has enrolled 61 students in its two programs, and by the end of the 1997 academic year, it will have graduated 19 FNPs and 19 CRNAs. The GSN was authorized by the Department of Defense, Office of Health Affairs, in February 1996. Federal nursing chiefs serve as advisors to the GSN. The GSN received full accreditation from the Council on Accreditation of Nurse Anesthesia Educational Programs in 1994 and from the National League for Nursing in December 1996. All students who have graduated have successfully passed their certification examinations. Supplementing other educational resources, the GSN is helping to meet the educational needs of the uniformed nursing services by introducing pilot programs specifically designed to meet these needs.

Accreditation↗
PubMed1998

Flow cytometric DNA analysis of invasive carcinomas detected by screening mammography: use of specimen mammography-guided fine-needle aspirates.

Clinical studies of flow cytometric DNA analysis of breast carcinoma are often limited by the lack of fresh tissue samples from smaller, nonpalpable carcinomas. In addition, most studies measuring DNA in the current literature focus on larger palpable masses that may have less relevance to the smaller, nonpalpable lesions. A prospective study of flow cytometric DNA analysis of in vitro specimen mammography-guided fine-needle aspirates (FNAs) of 103 consecutive nonpalpable invasive carcinomas detected by screening mammography was performed to determine efficacy and explore associations with mammographic and pathological features. For 62 (60%) lesions for which DNA analysis on both FNA and standard tissue incision samples was performed, there was excellent (89%) agreement for ploidy determinations (kappa=0.77) and poor agreement for S-phase percentage determinations (kappa=0.23). Specimen mammography-guided FNA analysis detected aneuploidy in 36% of lesions overall, including 34% of 41 lesions for which standard tissue procurement was not possible. Mammographic microcalcifications had a higher aneuploid rate (14 of 28 lesions, 50%) as compared with soft tissue masses (22 of 75 lesions, 29%), P < 0.01. Lobulated masses with indistinct margins had a higher aneuploid rate (5 of 6 lesions, 83%) as compared with more irregular, spiculated masses (7 of 27 lesions, 26%), P < 0.01. The aneuploidy rate was independent of specific histological diagnosis, lesion size, nuclear grade, or nodal or estrogen receptor status. Flow cytometric DNA analysis of mammographic lesion-specific, fresh, cellular FNA samples obtained under specimen mammographic guidance can assess early invasive carcinomas when gross fresh tissue procurement is not possible. This technique could be incorporated into larger clinical follow-up studies to determine the prognostic significance of flow cytometric DNA analysis for these very early breast carcinomas.

Adult↗
PubMed1997

Melanoma cell-cell interactions are mediated through heterophilic Mel-CAM/ligand adhesion.

Mel-cell adhesion molecule (CAM), also known as MUC18 and CD146, is a novel member of the immunoglobulin supergene family. Mel-CAM was first identified as an integral membrane glycoprotein in human melanoma and is also abundantly expressed by endothelial cells of various origins. In a previous study (I. M. Shih et al., Cancer Res., 54: 2514-2520, 1994), we showed that Mel-CAM is a cell-cell adhesion molecule with a possible role in melanoma invasion and metastasis. Here, we define the molecular mechanism responsible for cell-cell adhesion of Mel-CAM and demonstrate its role in melanoma-endothelial cell interactions. Most of human melanoma cells, including Mel-CAM-negative SBcl-2 cells, adhered to nitrocellulose-immobilized Mel-CAM produced by baculovirus recombinants. This adhesion can be blocked by full-length Mel-CAM or polyclonal antiserum against Mel-CAM. Adhesion is not affected by the presence of EDTA, truncated Mel-CAM extracellular domain, or heparan sulfate proteoglycan. In cell aggregation assays, Mel-CAM-negative SBcl-2 cells cluster with U937TM cells (U937 transfected with Mel-CAM cDNA) but not with control nontransfectants, suggesting that SBcl-2 cells express the ligand for Mel-CAM. SBcl-2 cells also form heterotypic aggregates with Mel-CAM-positive human endothelial cells but not with Mel-CAM-negative but ligand-positive smooth muscle cells. Taken together, our results show that Mel-CAM mediates cell-cell adhesion through heterophilic adhesion to an as yet unidentified ligand present on melanoma but not on endothelial cells. Thus, melanoma-endothelial interactions during metastasis may occur through this novel mechanism.

Antigens, CD↗