Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0278488 (metastatic breast cancer)
 7,812 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The development of new and effective marker substances has optimized tumor-marker-guided follow-up programs to monitor generalization of disease and to assess the therapeutic outcome. Isoferritins of placental origin were first determined in the serum of patients with lymphoproliferative disease by way of the recently developed monoclonal antibody CMH-9. We have set up an Austro-Israeli working group and analysed 64 patients in terms of the sensitivity of placental ferritin (PLF) compared with the standard markers carcinoembryonic antigen (CEA) and mucinous-like cancer-associated antigen (MCA) in patients with metastatic breast cancer. We have additionally evaluated the importance of combined marker determination. Analysis of the data in view of site of metastatic spread yielded satisfying results both for PLF (sensitivity 70.4%) as well as MCA (sensitivity 76.9%) for visceral metastases; a combination of these two markers revealed a striking sensitivity of 88.4%, which, however, could not be improved by adding the third marker (CEA). With regard to non-visceral metastases, CEA and MCA were clearly superior.
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PMID:Placental isoferritin (PLF) in comparison with MCA and CEA in advanced breast cancer--first data from a pilot study. 177 47

Forty-four patients with primary (n = 6), invasive (n = 19) and metastatic (n = 21) chest tumours underwent complete resection between 1986 and 1989 in a total of 46 consecutive procedures. Nineteen patients were female and 25 male; 2 patients, 1 male, 1 female, had second operations. The underlying disease was bronchial carcinoma in 17 (14 male), mesenchymal tumours in 17, metastatic breast cancer in 7 and miscellaneous in 5. The chest wall resection included up to 6 ribs. The manubrium was resected in 2 patients, the corpus sterni in 5. Pulmonary resection was performed in 36 cases in an en-bloc fashion. Other concomitant resections included the pericardium, diaphragm or transverse process of the vertebrae. Amputation of the right arm was necessary in two cases. Reconstruction of the thoracic cage was accomplished with PTFE soft tissue patches in 7, methyl methacrylate implants in 2, Marlex mesh in 1 and Vicryl net in 6 cases. In the majority of cases, particularly in dorso-apical and posterior defects, no substitutes were used. A variety of plastic procedures including the use of omentum, musculo- and fasciocutaneous flaps was employed for the reconstruction of the integument. There was no operative mortality. Fourteen patients died after surviving 2-25 months. Serious infection occurred in 1 patient and minor delay of healing in 2. Good palliation can be achieved at low risk. The effect on long-term survival remains uncertain, depending on the basic pathology.
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PMID:Surgery for primary, invasive and metastatic malignancy of the chest wall. 189 62

In 1976 we isolated a novel glycoprotein labeled EDC1, Mr 27,500, which is immunologically related to the normal plasma protein inter-alpha trypsin inhibitor (IATI, Mr 160,000) and which is the major component of cancer-associated proteinuria. Urinary excretion of EDC1 (mg/g creatinine) may be classified in four ranges: i) low (less than 15); ii) light (15-30); iii) intermediate (31-45); and iv) heavy (greater than 45). Normal healthy women excrete 8.0 +/- 2.2 mg/g creatinine (average +/- SEM), whereas patients with metastatic breast cancer excrete 98.2 +/- 11.6 mg/g creatinine. Patients with a variety of non-malignant disorders excreted 14.6 +/- 4 mg EDC1/g creatinine, but patients with renal failure, rheumatoid arthritis, and infectious diseases averaged 130.3 +/- 60. Sixty-five to 95 percent of urinary immunoreactive EDC1 in the latter group was of higher molecular weight, perhaps reflecting increased renal clearance of plasma IATI. In patients undergoing excisional biopsy of breast lesions, preoperative EDC1 excretion was 21.5 +/- 3.4 in those whose lesions were benign and 43.1 +/- 7.6 in those whose lesions were malignant. Eight of these latter patients were heavy excretors; EDC1 excretion fell postoperatively in these patients. In normal serum the immunoreactive IATI (IR-IATI) exists in three molecular weight forms 160,000, 120,000 and 58,000. In patients who were heavy excretors of EDC1, the IR-IATI corresponding to Mr 58,000 was absent and total serum IR-IATI was about two-thirds of normal. There was also a negative correlation between serum levels of IATI and urinary EDC1 in these patients. These data suggest that urinary EDC1 may arise as a result of interaction between IATI and tumor-associated proteases.
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PMID:Urinary cancer-related protein EDC1 and serum inter-alpha trypsin inhibitor in breast cancer. 608

Several investigators have shown that the expression of the sialyl-Tn (STn) epitope on cancer associated mucins is associated with a poor prognosis in several human cancers suggesting that STn may have functional significance in metastasis. We postulate that antibodies against the STn-epitope can inhibit metastasis. We generated a synthetic "mimic", NANA alpha (2-->6)GalNAc alpha-O-Crotyl (STn-crotyl), of the natural O-linked epitope on mucins, NANA alpha (2-->6)GalNAc alpha-O-Serine (STn-serine). STn-crotyl was conjugated to the carrier protein KLH through the crotyl linker arm and a "vaccine" containing STn-KLH plus Detox adjuvant was formulated. The immunogenicity of the vaccine was evaluated in BALB/c mice and in metastatic breast cancer patients. The specificity and titres of IgG antibodies were evaluated by ELISA on ovine submaxillary mucin (OSM) solid phases. OSM is a convenient source of repeating, natural O-linked STn-serine structures. Mice immunized three times with as little as 0.25 microgram of STn-KLH produced a median IgG titre of over 1:5000 on solid phase OSM. Anti-OSM IgG monoclonal antibodies generated from these mice were completely inhibited in their binding to solid phase OSM equally well by STn-serine and STn-crotyl synthetic haptens but not by several other closely related synthetic haptens. Breast cancer patients immunized 2-8 times with 25 or 100 micrograms of the same vaccine produced median peak IgG titres 1:1280 measured on STn-HSA and 1:80 on OSM. Once again, hapten inhibition experiments with the human sera demonstrated the specificities of the IgG antibodies for STn-crotyl and STn-serine, but not against several other related synthetic haptens. We found little or no evidence that the artificial linker arm (crotyl linker) contributed significantly to either the titre or affinity of the antibodies generated in either mice or human breast cancer patients. This suggests that the antibodies recognized the cancer-associated disaccharide NANA alpha (2-->6)GalNAc. Evidence of a clinical response was noted in several of the immunized breast cancer patients with other patients showing prolonged disease stability.
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PMID:Specificity of the IgG response in mice and human breast cancer patients following immunization against synthetic sialyl-Tn, an epitope with possible functional significance in metastasis. 752 78

We generated a synthetic epitope, NANA alpha(2-6) GalNAc alpha-O-Crotyl (STn-crotyl), designed to "mimic" the natural O-linked epitope expressed on human carcinoma cells, NANA alpha(2-6)GalNAc alpha-O-Serine (STn-serine). STn-crotyl was conjugated to the carrier protein KLH through the crotyl linker arm, and a "vaccine" containing STn-KLH plus DETOX adjuvant was formulated. The immunogenicity of the vaccine was evaluated preclinically in CAF1 mice and subsequently in patients with metastatic breast cancer. The specificity and titers of IgG antibodies were evaluated by kinetic ELISA on synthetic STn-HSA and on ovine submaxillary mucin (OSM) solid phases. Ovine submaxillary mucin is a convenient source of repeating, natural O-linked STn-serine structures. Mice immunized three times with as little as 0.25 micrograms of STn-KLH produced IgG titers ranging from 1:10(4) to 1:10(5) when tested on solid phase OSM. Anti-OSM IgG, both polyclonal and monoclonal antibodies, generated from these mice were completely inhibited in their binding to solid phase OSM equally well by STn-serine and STn-crotyl synthetic haptens but not by several other closely related synthetic haptens. These monoclonal antibodies also bound to STn determinants on human tumor cell surfaces. Breast cancer patients immunized with 100 micrograms of the same vaccine produced median peak IgG titers 1:1280 measured on STn-HSA and 1:160 on OSM. Hapten inhibition experiments with the human sera demonstrated the specificities of the IgG antibodies for STn-crotyl and STn-serine, but not against several other related synthetic haptens. We found little evidence that the artificial linker arm (crotyl linker) contributed substantially to either the titer or affinity of the antibodies generated in either mice or human breast cancer patients. This suggests that the antibodies recognized the cancer-associated disaccharide NANA alpha(2-->6)-GalNAc. Small but not large doses of STn-KLH immunogen induced anti-STn DTH responses in mice that were inversely proportional to the antibody responses. Evidence of a clinical response was noted in some of the immunized breast cancer patients, with other patients showing prolonged disease stability.
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PMID:Immune responses of mice and human breast cancer patients following immunization with synthetic sialyl-Tn conjugated to KLH plus detox adjuvant. 769 Feb 15

Real-time RT-PCR is a relatively new technology that uses an online fluorescence detection system to determine gene expression levels. It has the potential to significantly improve detection of breast cancer metastasis by virtue of its exquisite sensitivity, high throughput capacity and quantitative readout system. To assess the utility of this technology in breast cancer staging, we determined the relative expression levels of 12 cancer-associated genes (mam, PIP, mamB, CEA, CK19, VEGF, erbB2, muc1, c-myc, p97, vim and Ki67) in 51 negative-control normal lymph nodes and in 17 histopathology-positive ALNs. We then performed a receiver operating characteristic (ROC) curve analysis to determine the sensitivity and specificity levels of each gene. Areas under the ROC curve indicated that the most accurate diagnostic markers were mam (99.6%), PIP (93.3%), CK19 (91.0%), mamB (87.9%), muc1 (81.5%) and CEA (79.4.0%). mam was overexpressed in 16 of 17 lymph nodes known to contain metastatic breast cancer at levels ranging from 22- to 2.8 x 10(5)-fold above normal mean expression, whereas PIP was overexpressed from 30- to 2.2 x 10(6)-fold above normal in 13 lymph nodes. Real-time RT-PCR analysis of pathology-negative LN from breast cancer patients revealed evidence of overexpression of PIP (6 nodes), mam (3 nodes) and CEA (1 node) in 8 of 21 nodes (38%). Our results provide evidence that mam, PIP, CK19, mamB, muc1 and CEA can be applied as a panel for detection of metastatic and occult micrometastatic disease.
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PMID:Quantitative real-time RT-PCR detection of breast cancer micrometastasis using a multigene marker panel. 1141 Aug 61

The authors report their experience with 42 patients in whom anterior lumbar fusion was performed using titanium cages as a versatile adjunct to treat a wide variety of spinal deformity and pathological conditions. These conditions included congenital, degenerative, iatrogenic, infectious, traumatic, and malignant disorders of the thoracolumbar spine. Fusion rates and complications are compared with data previously reported in the literature. Between July 1996 and July 1999 the senior authors (C.I.S., R.P.N., and M.J.R.) treated 42 patients by means of a transabdominal extraperitoneal (13 cases) or an anterolateral extraperitoneal approach (29 cases), 51 vertebral levels were fused using titanium cages packed with autologous bone. All vertebrectomies (27 cases) were reconstructed using a Miami Moss titanium mesh cage and Kaneda instrumentation. Interbody fusion (15 cases) was performed with either the BAK titanium threaded interbody cage (in 13 patients) or a Miami Moss titanium mesh cage (in two patients). The average follow-up period was 14.3 months. Seventeen patients had sustained a thoracolumbar burst fracture, 12 patients presented with degenerative spinal disorders, six with metastatic tumor, four with spinal deformity (one congenital and three iatrogenic), and three patients presented with spinal infections. In five patients anterior lumbar interbody fusion (ALIF) was supplemented with posterior segmental fixation at the time of the initial procedure. Of the 51 vertebral levels treated, solid arthrodesis was achieved in 49, a 96% fusion rate. One case of pseudarthrosis occurred in the group treated with BAK cages; the diagnosis was made based on the patient's continued mechanical back pain after undergoing L4-5 ALIF. The patient was treated with supplemental posterior fixation, and successful fusion occurred uneventfully with resolution of her back pain. In the group in which vertebrectomy was performed there was one case of fusion failure in a patient with metastatic breast cancer who had undergone an L-3 corpectomy with placement of a mesh cage. Although her back pain was immediately resolved, she died of systemic disease 3 months after surgery and before fusion could occur. Complications related to the anterior approach included two vascular injuries (two left common iliac vein lacerations); one injury to the sympathetic plexus; one case of superficial phlebitis; two cases of prolonged ileus (greater than 48 hours postoperatively); one anterior femoral cutaneous nerve palsy; and one superficial wound infection. No deaths were directly related to the surgical procedure. There were no cases of dural laceration and no nerve root injury. There were no cases of deep venous thrombosis, pulmonary embolus, retrograde ejaculation, abdominal hernia, bowel or ureteral injury, or deep wound infection. Fusion-related complications included an iliac crest hematoma and prolonged donor-site pain in one patient. There were no complications related to placement or migration of the cages, but there was one case of screw fracture of the Kaneda device that did not require revision. The authors conclude that anterior lumbar fusion performed using titanium interbody or mesh cages, packed with autologous bone, is an effective, safe method to achieve fusion in a wide variety of pathological conditions of the thoracolumbar spine. The fusion rate of 96% compares favorably with results reported in the literature. The complication rate mirrors the low morbidity rate associated with the anterior approach. A detailed study of clinical outcomes is in progress. Patient selection and strategies for avoiding complication are discussed.
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PMID:Anterior lumbar fusion with titanium threaded and mesh interbody cages. 1691 6

An extensive family of UDP-N-alpha-d-galactosamine: polypeptide N-acetylgalactosaminyltransferases (polypeptide N-acetylgalactosaminyltransferases, ppGalNAc-T's) catalyse the attachment of the first N-acetylgalactosamine (GalNAc) monosaccharide to the polypeptide at the initiation of O-linked glycosylation of proteins. Some members of the family are broadly expressed while others are more restricted in their distribution, their expression and activity being confined to certain cells or tissues, being associated with physiological states or differentiation. Their careful regulation, which is not well understood, may mediate the synthesis of varied glycoforms of cellular proteins with different biological activities. Disruptions in glycosylation are a common feature of cancer and may have functional significance. Immunocytochemistry with confocal scanning laser microscopy was employed to detect members of the ppGalNAc-T family, ppGalNAc-T1, -T2, -T3, -T4 and -T6 in a range of breast cell lines. The cells were chosen to represent a range of phenotypes from 'normal'/benign (HMT 3,522), primary, non-metastatic breast cancer (BT 474), to aggressive, metastatic breast cancer (ZR75-1, T47D, MCF-7, DU 4,475). They stably synthesise varying levels, consistent with origin and phenotype, of aberrantly glycosylated glycoproteins featuring exposed, terminal GalNAc residues, including the cancer-associated Tn antigen, which, in numerous studies, have been associated with metastatic competence and poor cancer prognosis. GalNAc-T1 and -T2 were detectable at low levels in all cell lines studied. ppGalNAc-T4, which has never been described in breast, was very weakly detectable in BT 474, MCF7 and T47D. ppGalNAc-T3 and -T6 were weakly detectable or undetectable, respectively, in the cell line HMT 3,522 derived from 'normal'/benign breast epithelium, but were readily detectable in all malignant cell lines. Thus, a broader range of ppGalNAc-T's were detectable in the malignant cell lines in comparison to the 'normal'/benign cells, where only the 'housekeeping' ppGalNAc-T1 and -T2 were present. Expression of normally tightly restricted ppGalNAc-T's may result in initiation of O-linked glycosylation at normally unoccupied potential glycosylation sites leading to altered glycoforms of proteins with changed biological activity which may contribute to the pathogenesis of cancer.
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PMID:Immunolocalisation of members of the polypeptide N-acetylgalactosaminyl transferase (ppGalNAc-T) family is consistent with biologically relevant altered cell surface glycosylation in breast cancer. 1744 26

Carcinoma are complex societies of mutually interacting cells in which there is a progressive failure of normal homeostatic mechanisms, causing the parenchymal component to expand inappropriately and ultimately to disseminate to distant sites. When a cancer cell metastasizes, it first will be exposed to cancer associated fibroblasts in the immediate tumor microenvironment and then to normal fibroblasts as it traverses the underlying connective tissue towards the bloodstream. The interaction of tumor cells with stromal fibroblasts influences tumor biology by mechanisms that are not yet fully understood. Here, we report a role for normal stroma fibroblasts in the progression of invasive tumors to metastatic tumors. Using a coculture system of human metastatic breast cancer cells (MCF10CA1a) and normal murine dermal fibroblasts, we found that medium conditioned by cocultures of the two cell types (CoCM) increased migration and scattering of MCF10CA1a cells in vitro, whereas medium conditioned by homotypic cultures had little effect. Transient treatment of MCF10CA1a cells with CoCM in vitro accelerated tumor growth at orthotopic sites in vivo, and resulted in an expanded pattern of metastatic engraftment. The effects of CoCM on MCF10CA1a cells were dependent on small amounts of active TGF-beta1 secreted by fibroblasts under the influence of the tumor cells, and required intact ALK5-, p38-, and JNK signaling in the tumor cells. In conclusion, these results demonstrate that transient interactions between tumor cells and normal fibroblasts can modify the acellular component of the local microenvironment such that it induces long-lasting increases in tumorigenicity and alters the metastatic pattern of the cancer cells in vivo. TGF-beta appears to be a key player in this process, providing further rationale for the development of anti-cancer therapeutics that target the TGF-beta pathway.
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PMID:Transient tumor-fibroblast interactions increase tumor cell malignancy by a TGF-Beta mediated mechanism in a mouse xenograft model of breast cancer. 2035 26

We analyzed the expression and clinical role of endoglin (CD105) in breast carcinoma effusions. Endoglin levels were measured in 36 effusion supernatants by ELISA and studied for association with the cancer-associated markers calprotectin, VEGF, and the VEGF receptor sFlt1. Endoglin expression was further studied in 46 effusions and 22 primary carcinomas using immunohistochemistry. The four secreted molecules were detected in all specimens and their levels significantly correlated (p < 0.001). In effusions, endoglin was localized to carcinoma cells and reactive mesothelium using immunohistochemistry. Tumor cell expression was higher in effusions compared to primary carcinomas (p = 0.025), and in post-chemotherapy compared to pre-chemotherapy effusions (p = 0.017). Higher tumor endoglin expression was associated with poor overall (p = 0.021) and disease-free (p = 0.032) survival in univariate analysis, and was an independent predictor in Cox multivariate analysis (p = 0.001 and p = 0.038, respectively). Our data suggest that endoglin may be an important therapeutic target in metastatic breast cancer.
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PMID:CD105 (Endoglin) expression in breast carcinoma effusions is a marker of poor survival. 2107 85


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