Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.10.1 (ERK)
95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report two cases treated with primary chemotherapy containing trastuzumab with a review of some important papers. The first patient was a 43-year-old female. A 33-mm left breast invasive ductal carcinoma (ER (-), PgR (-), HER2 3+(IHC) ) with several lymph node metastases in the Ax, Ic and Sc was found. After primary chemotherapy with 6 courses of EC and 4 courses of weekly paclitaxel + trastuzumab, the efficacy for the local tumor was judged as PR. However, brain metastases appeared, so the operation was canceled. Brain metastases were then treated by gamma-knife three times, but systemic chemotherapy was not administered. Eight months later, carcinomatous meningitis appeared. Intrathecal chemotherapy with MTX+Ara-C was started, but the patient died after 20 months from the beginning of the treatment. Local efficacy was judged as CR. The second patient was a 41-year-old female. A 39-mm right breast invasive ductal carcinoma (ER (-), PgR (-), HER2 3+(IHC) ) with two lymph node metastases in the Ax was found. After primary chemotherapy with 6 courses of FEC and 4 courses of weekly paclitaxel + trastuzumab, the efficacy was judged as PR. The operation was scheduled, but he patient wished to continue chemotherapy for cosmetic reasons. Later, because of mild tumor regrowth, we used 2 courses of vinorelbine in combination with trastuzumab. The tumor grew more, so Bp + Ax was done. The woman is alive at this writing with no recurrence.
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PMID:[Two cases treated with trastuzumab as primary chemotherapy]. 1794 Mar 91

We report a case of elderly metastatic breast cancer with a complete response to the treatment with XC (X: capecitabine and C: cyclophosphamide). A 78-year-old woman, who presented with left breast cancer, underwent pectoralis-preserving mastectomy when she was 76 years old. Pathological findings were as follows: invasive ductal carcinoma (scirrhous type), pT1c (2.0 cm), n (1/10), ly3, v1, ER (-), PgR (-), HER2: score 1. After one year and a half, a left supraclavicular lymph node metastasis, a left interpectoral lymph node metastasis, and mediastinal lymph nodes metastasis were noted. Capecitabine and cyclophosphamide were administered as first-line chemotherapy. After 8 cycles, all metastases responded, and this therapy is now being continued (19 cycles) on an outpatient basis. The complete response has continued for nine months. XC therapy can be the first-line chemotherapy for elderly metastatic breast cancer patients since it has been effective and no serious side effects have been encountered while maintaining quality of life.
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PMID:[A case of elderly metastatic breast cancer with a complete response to treatment with capecitabine and cyclophosphamide]. 1794 Mar 94

Basal-like breast carcinoma is an aggressive form of breast cancer, characterized by the absence of oestrogen receptor and HER2 expression, the presence of cytokeratin 5 and epidermal growth factor receptor expression, and by the up-regulation of stem cell regulatory genes. We show here that tumour tissues expressing high levels of SLUG mRNA show a basal-like breast carcinoma phenotype and that such tumours also express high levels of stem cell-regulatory genes, ie CD133, Bmi1. Further, we show that stem/progenitor cells, isolated from ductal breast carcinoma and from normal mammary gland as mammospheres, express SLUG, CD133, and Bmi1 mRNA and show a phenotype similar to that of basal-like breast carcinoma. We also report that SLUG expression in tumour tissues correlates with that of the hypoxia survival gene carbonic anhydrase IX. In this regard, we report that the exposure of SLUG-negative/luminal-like MCF-7 cells to a hypoxic environment promotes the onset of the basal-like breast carcinoma phenotype, together with up-regulation of the SLUG gene, which in turn blunts oestrogen receptor-alpha and boosts carbonic anhydrase IX gene expression. Finally, we show that SLUG expression promotes the invasiveness of MCF-7 cells exposed to hypoxia and sustains the in vivo aggressiveness of hypoxia-selected, MCF-7-derived cells in xenografts. These data indicate that SLUG gene expression is part of a hypoxia-induced genetic programme which sets up a basal/stem cell-like, aggressive phenotype in breast cancer cells.
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PMID:The basal-like breast carcinoma phenotype is regulated by SLUG gene expression. 1797 39

Programmed cell death 4 gene (PDCD4), an in vivo repressor of transformation, was originally isolated from a human glioma library by screening it with an antibody against a nuclear antigen in proliferating cells. PDCD4 functions as a transformation repressor by inhibiting the activity of the RNA helicase, eIF4A. We previously showed that retinoids, anti-estrogens and HER2/neu antagonist induce PDCD4 expression in human breast cancer cell lines. Very little is known about the expression of PDCD4 in human breast cancer tissues or the significance of the PDCD4 expression in breast cancer. To gain insight into the pattern of the PDCD4 expression in breast tissues, we performed an immunohistochemical analysis of the PDCD4 expression in 80 archived, normal and ductal breast carcinoma tissues (invasive and carcinoma in situ) (DCIS) and correlated PDCD4 expression with expression of known prognostic markers in breast cancer (ER, PR and HER2/neu). To assess the role of methylation on PDCD4 expression in breast cancer cells, breast cancer cell lines were treated with the demethylating agent 5-deoxy-azacytidine and analyzed for PDCD4 expression. We observed primarily nuclear localization of PDCD4 in ductal carcinoma in situ compared to normal breast tissues where the PDCD4 expression was predominantly cytoplasmic. This was seen more frequently in DCIS cases that were ER positive and HER2/neu negative samples. PDCD4 expression was markedly decreased in the invasive ductal carcinoma. We did not observe any significant relationship between PDCD4 expression and the expression of RAR or PR. In T-47D, MDA-MB-435 and MDA-MB-231 cells, treatment with 5-deoxy-azacytidine did not result in an increased expression of PDCD4. The present study demonstrated altered cellular localization of PDCD4 when comparing normal breast to neoplastic breast tissues. In addition, there was a decreased expression of PDCD4 in breast cancer when compared with normal breast tissue. A loss of the PDCD4 expression in breast cancer cell lines does not appear to result from hypermethylation of the PDCD4 promoter.
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PMID:Alterations in the expression of PDCD4 in ductal carcinoma of the breast. 1798 21

Spontaneous mammary gland carcinomas occurred in five baboons during a 13-year period at Southwest Foundation for Biomedical Research. The affected baboons ranged in age from 21 to 33 years. Menopause in the baboon occurs at approximately 26 years of age. All five animals had typical invasive ductal carcinoma. Morphologically, the tumors were characterized by neoplastic cells arranged from pseudopapillary and cribiform to more poorly differentiated solid cellular growth patterns. Additional features included lack of tubule formation (4/5), marked nuclear pleomorphism (5/5), a high mitotic rate (4/5) and tumor necrosis (4/5). Applying a grading system used for breast cancer in women, four tumors were graded as poorly differentiated carcinomas and one was graded as moderately differentiated. Co-existent ductal carcinoma in situ (DCIS) was observed in three of the mammary tumors. Metastases to the regional lymph nodes were confirmed in two animals, both with histological evidence of lymphovascular invasion in the primary tumor. Distant metastases were observed in only one animal. Immunohistochemical staining for human therapeutic markers revealed 2/5 tumors strongly positive for estrogen receptor, 1/5 strongly positive for progesterone receptor and 4/4 negative for HER2 expression. Although the incidence appears to be low, these five cases of mammary carcinoma in female baboons suggest that when present baboon mammary carcinoma is usually of ductal origin and behaves similar to a human breast carcinoma.
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PMID:Characterization of spontaneous mammary gland carcinomas in female baboons. 1819 73

We report a case of advanced breast cancer (T4b, N3c, M1) achieving a significant improvement on QOL by multi-disciplinary therapy and S-1 administration. The patient was a 59-year-old woman who had ulcerative breast lump with bleeding. A core needle biopsy for breast tumor led to a diagnosis of an invasive ductal carcinoma negative for estrogen receptor, progesterone receptor, and HER2/neu protein expression. The aspiration biopsy cytology was performed from skin lesion, the diagnosis was class V. She received 6 cycles of tri-weekly CEF (C: 500 mg, E: 60 mg, F: 500 mg/m2) therapy. The effect of the breast tumor was partial response, and the bleeding from the breast lump was improved. But the response from metastatic skin tumor was less satisfactory. We performed a radiation therapy (20 Gy) to metastatic skin tumor, and the lesion disappeared after the radiation therapy. Then, we tried docetaxel, but the side effect appeared. So, we started administering S-1 after docetaxel. One year later, she was estimated to be in the long stable disease. Multi-disciplinary therapy can improve a patient QOL and the clinical outcomes in Stage IV advanced breast cancer.
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PMID:[A case of advanced breast cancer successfully treated with multi-disciplinary therapy and S-1 administration]. 1821

There are 4 major molecular classifications in the literature that divide breast carcinoma into basal and nonbasal subtypes, with basal subtypes associated with poor prognosis. Basal subtype is defined as positive for cytokeratin (CK) 5/6, CK14, and/or CK17 in CK classification; negative for ER, PR, and HER2 in triple negative (TN) classification; negative for ER and negative or positive for HER2 in ER/HER2 classification; and positive for CK5/6, CK14, CK17, and/or EGFR; and negative for ER, PR, and HER2 in CK/TN classification. These classifications use similar terminology but different definitions; it is critical to understand the precise relationship between them. We compared these 4 classifications in 195 breast carcinomas and found that (1) the rates of basal subtypes varied from 5% to 36% for ductal carcinoma in situ and 14% to 40% for invasive ductal carcinoma. (2) The rates of basal subtypes varied from 19% to 76% for HG carcinoma and 1% to 7% for NHG carcinoma. (3) The rates of basal subtypes were strongly associated with tumor grades (P < .001) in all classifications and associated with tumor types (in situ versus invasive ductal carcinomas) in TN (P < .001) and CK/TN classifications (P = .035). (4) These classifications were related but not interchangeable (kappa ranges from 0.140 to 0.658 for HG carcinoma and from 0.098 to 0.654 for NHG carcinoma). In conclusion, although these classifications all divide breast carcinoma into basal and nonbasal subtypes, they are not interchangeable. More studies are needed to evaluate to their values in predicting prognosis and guiding individualized therapy.
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PMID:Molecular classifications of breast carcinoma with similar terminology and different definitions: are they the same? 1828 38

BRCA1 is a tumor suppressor gene which, when mutated, is associated with the development of hereditary breast cancers. In sporadic tumors, although inherent gene mutations are rare, loss of BRCA1, resulting from reduced expression or incorrect subcellular localization, is postulated to be important. The purpose of the current study was to examine the expression and localization of BRCA1 protein and to assess its prognostic value, in a well-characterized series of unselected breast carcinomas. We have examined BRCA1 in a series of invasive breast carcinoma (1940 cases) using tissue microarray and immunohistochemistry, to evaluate its expression pattern and to correlate this with clinicopathologic variables and patient outcome. In breast cancer, complete loss of nuclear expression was observed in 223 cases (15%) and cytoplasmic expression was found in 541 breast cancers (36.6%). Absent or reduced nuclear BRCA1 expression was observed more frequently in ductal carcinoma of no special type and medullary-like carcinoma and less frequently in lobular and tubular mixed carcinomas. It was also associated with high-grade, advanced lymph node stage, larger size, vascular invasion, negative estrogen receptor, progesterone receptor and androgen receptor expression, and positive p53 and P-cadherin expression, and with the basal-like class of breast cancer. Altered BRCA1 was associated with shorter disease-free interval. Cytoplasmic expression was also associated with development of recurrence and positive EGFR and HER2 expression. It showed an inverse association with survival particularly in low-grade, small-size, and estrogen receptor-positive subgroups. In the grade 1 subgroup, multivariate analysis with adjustment for other prognostic factors showed that cytoplasmic expression of BRCA1 was an independent predictor of disease-free interval. BRCA1 alteration may play a significant role in the development and progression of breast cancer. Immunohistochemical assessment of BRCA1 expression could provide additional clinically relevant information in routine classification of breast cancer.
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PMID:Expression of BRCA1 protein in breast cancer and its prognostic significance. 1840 Feb 53

A 60-year-old woman was admitted to the hospital with left thigh pain. She had undergone mastectomy and axillary lymph node dissection for right breast cancer (T3N2M0) five years and two months earlier. The pathological diagnosis then was invasive ductal carcinoma with axillaryly mph node metastases. Hormone receptors and HER2 status were negative and positive (3+), respectively. The patient received adjuvant chemotherapy and radiotherapy, but bone metastases appeared 18 months after surgery. Although trastuzumab-combination chemotherapy with taxane and/or capecitabine was given, bone metastases in thoracic vertebra resulted in incomplete paralysis in both legs. She underwent thoraco-lumbar vertebral fixation 10 months before admission. A PET/CT revealed multiple bone metastases in the left femur as well as vertebrae, and CEA rose markedly. She received radiotherapy and trastuzumab monotherapy in addition to bisphosphonate. Temporarily, CEA decreased, but because recurrence nests were recognized in the supraclavicle and mediastinum after the eight-month treatment, trastuzumab monotherapy was followed by trastuzumab plus vinorelbine combined therapy. This regimen markedly reduced CEA after three months, but it rose again over the following three months. As S-1-combined therapy was not effective, trastuzumab+gemcitabine (1 g/week and two weeks on/one week off) combined therapy was started. CEA decreased markedly after 4 cycles, and FDG accumulation in the recurrence region was markedly improved. The adverse event during this treatment was minor, and PS was sufficiently maintained. These results suggest that trastuzumab plus gemcitabine combination therapy is effective for HER2-positive metastatic breast cancer.
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PMID:[A case of HER2-positive metastatic breast cancer responding to trastuzumab plus gemcitabine combination therapy]. 1840 45

Pleomorphic lobular carcinomas (PLC) of the breast display histological features associated with classic invasive lobular carcinoma (ILC), yet they also exhibit more conspicuous nuclear atypia and pleomorphism, and an aggressive clinical behaviour. From a breast cancer progression perspective, it is unclear whether PLC is a variant of ILC or is a high-grade invasive ductal carcinoma (IDC) that has lost E-cadherin. The molecular features of 26 PLC were studied using immunohistochemistry [oestrogen receptor (ER), progesterone receptor (PR), HER2, p53 and E-cadherin], 0.9 Mb resolution, microarray-based comparative genomic hybridization (aCGH), fluorescent (FISH) and chromogenic (CISH) in situ hybridization and loss of heterozygosity. Comparative analysis was performed with aCGH data from PLC with classic ILC (16 cases) and high grade IDC (35 cases). PLCs were frequently ER- and PR-positive, E-cadherin-negative and occasionally HER2- and p53-positive. Recurrent copy number changes identified by aCGH included gains on 1q, 8q, 11q, 12q, 16p and 17q and losses on 8p, 11q, 13q, 16q and Xq. Highly recurrent 1q+ (100% of cases), 16p+ (93%), 11q- (53%) and 16q- (93%) and evidence of the der(1;16)/der(16)t(1;16) rearrangement, as detected by FISH, suggested that PLC had a 'lobular genotype'. Focal amplifications were evident at 8p12-p11, 8q24, 11q13.1-q14.1, 12q14, 17q12 and 20q13. Loss of BRCA2 was detected in 40% of PLC by LOH. Comparative analysis of aCGH data suggested the molecular features of PLC (ER/PR-positive, E-cadherin-negative, 1q+, 11q(-), 16p+ and 16q(-)) were more closely related to those of ILC than IDC, implicating an overlapping developmental pathway for these lobular tumour types. Molecular alterations found in PLC that are more typical of high-grade IDC than ILC (p53 and HER2 positivity, 8q+, 17q24-q25+, 13q(-) and amplification of 8q24, 12q14, 17q12 and 20q13) are likely to drive the high-grade and more aggressive biology of PLC.
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PMID:Molecular profiling pleomorphic lobular carcinomas of the breast: evidence for a common molecular genetic pathway with classic lobular carcinomas. 1847 30


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