1/37. Isolation and characterization of a new human breast cancer cell line, KPL-4, expressing the Erb B family receptors and interleukin-6.A new human breast cancer cell line, KPL-4, was recently isolated from the malignant pleural effusion of a breast cancer patient with an inflammatory skin metastasis. This cell line can be cultured under serum-free conditions and is tumorigenic in female athymic nude mice. Flow cytometric analysis revealed the expression of Erb B-1, -2 and -3. Dot blot hybridization showed a 15-fold amplification of the erb B-2. reverse transcription-polymerase chain reaction analysis showed a detectable level of mRNA expression of all the Erb B family receptors. In addition, all the receptors were autophosphorylated under a serum-supplemented condition. Unexpectedly, transplanted KPL-4 tumours induced cachexia of recipient mice. A high concentration of interleukin-6 (IL-6) was detected in both the culture medium and the serum of mice. The weight of tumours significantly correlated with the serum IL-6 level. The antiproliferative effect of a humanized anti-Erb B-2 monoclonal antibody, rhuMAbHER2, was investigated. This antibody significantly inhibited the growth of KPL-4 cells in vitro but modestly in vivo. Loss of mouse body weight was partly reversed by rhuMAbHER2. These findings suggest that KPL-4 cells may be useful in the development of new strategies against breast cancer overexpressing the Erb B family receptors and against IL-6-induced cachexia.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
2/37. Characterization of human MMTV-like (HML) elements similar to a sequence that was highly expressed in a human breast cancer: further definition of the HML-6 group.Previously, we found a retroviral sequence, HML-6.2BC1, to be expressed at high levels in a multifocal ductal breast cancer from a 41-year-old woman who also developed ovarian carcinoma. The sequence of a human genomic clone (HML-6.28) selected by high-stringency hybridization with HML-6.2BC1 is reported here. It was 99% identical to HML-6.2BC1 and gave the same restriction fragments as total dna. HML-6.28 is a 4.7-kb provirus with a 5'LTR, truncated in RT. Data from two similar genomic clones and sequences found in GenBank are also reported. Overlaps between them gave a rather complete picture of the HML-6.2BC1-like human endogenous retroviral elements. work with somatic cell hybrids and FISH localized HML-6.28 to chromosome 6, band p21, close to the MHC region. The causal role of HML-6.28 in breast cancer remains unclear. Nevertheless, the ca. 20 Myr old HML-6 sequences enabled the definition of common and unique features of type A, B, and D (ABD) retroviruses. In Gag, HML-6 has no intervening sequences between matrix and capsid proteins, unlike extant exogenous ABD viruses, possibly an ancestral feature. Alignment of the dUTPase showed it to be present in all ABD viruses, but gave a phylogenetic tree different from trees made from other ABD genes, indicating a distinct phylogeny of dUTPase. A conserved 24-mer sequence in the amino terminus of some ABD envelope genes suggested a conserved function.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
3/37. Cushing's syndrome secondary to ectopic ACTH secretion from metastatic breast carcinoma.breast carcinoma is a rare cause of ectopic ACTH syndrome. There are only two previously reported cases in which ACTH secretion is documented. We describe the case of a 56-year-old woman who presented with clinical and biochemical features of ectopic ACTH syndrome in the setting of metastatic breast carcinoma. Despite aggressive management of her ectopic ACTH syndrome, her course was complicated by opportunistic infection, respiratory failure and death. Immunostaining of the breast metastases for ACTH was positive and in situ hybridization revealed proopiomelanocortin gene expression. This is the first reported case of ectopic ACTH syndrome associated with metastatic breast cancer in which the technique of in situ hybridization has been used to confirm the breast cancer metastases as the source of ectopic ACTH secretion.- - - - - - - - - - ranking = 2keywords = hybridization (Clic here for more details about this article) |
4/37. Lymphoepithelioma-like carcinoma of the breast. An unusual pattern of infiltrating lobular carcinoma.A case of breast carcinoma, showing both lymphoepithelioma-like and lobular infiltrating carcinoma, is described, which must be distinguished from the medullary carcinoma with which it shares some features, such as the strong lymphocytic infiltration, but not sharp circumscription, syncytial growth pattern, nuclear pleomorphism, and high mitotic rate. Unlike the lymphoepithelial carcinoma of the nasopharynx and some lympho-epithelioma-like carcinomas of the lung, stomach, salivary glands, and thymus, it does not seem to be connected with Epstein-Barr virus (EBV) infection, as shown by negative results of both in situ hybridization and polymerase chain reaction. This neoplasia may be defined as a peculiar form of lobular carcinoma, therefore, more representative of an unusual microscopic pattern than a distinctive clinicopathologic entity in itself.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
5/37. Primary hepatic leiomyosarcoma in a woman after renal transplantation: report of a case.In contrast to malignant lymphomas or skin cancer, smooth muscle tumors including leiomyosarcoma are rarely associated with transplant recipients. We herein present a 33-year-old woman with end-stage renal disease who received a transplant at 27 years of age. Four years after the transplantation, at age 31, she underwent a mastectomy because of primary right breast cancer, which was found to be a 5-mm-sized mucinous carcinoma with no regional lymph node metastasis. Six years after the transplantation, a liver tumor was unexpectedly discovered. An explorative laparotomy revealed a well-encapsulated tumor occupying the posterior portion of the right lobe of the liver. The patient underwent a posterior segmentectomy. Histologically, the tumor possessed intermingling fascicles of spindle cells with eosinophilic cytoplasm and elongated nuclei. Based on an immunohistochemical examination, the tumor cells were positive for the muscle-associated antibody. In addition, rna probes for Epstein-Barr virus were negative based on in situ hybridization. The histologic, immunohistochemical findings were considered to be diagnostic for leiomyosarcoma, which is a low-grade malignancy. Two years after surgery, the patient is doing well with no recurrence of liver tumors or breast cancer.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
6/37. Atypical t(15;17)(q13;q12) in a patient with all-trans retinoic acid refractory secondary acute promyelocytic leukemia: a case report and review of the literature.A 69-year-old woman developed microgranular acute promyelocytic leukemia (APL-M3) 10 months after receiving adjuvant cyclophosphamide, doxorubicin, and paclitaxel for breast cancer. Replicate bone marrow aspirate karyotypes contained a translocation between the long arms of chromosomes 15 and 17, but not at breakpoints typical for APL. fluorescence in situ hybridization paints and RARalpha/PML cosmid probes verified that the breakpoints on chromosomes 15 and 17 were proximal to both the PML and RARalpha genes; t(15;17)(q13;12). Although the patient received induction chemotherapy and a several month trial of all-trans retinoic acid (ATRA), there was no clinical improvement or hematological remission. We suspect that this patient developed postchemotherapy secondary APL with an atypical t(15;17), which rendered her leukemic cells unresponsive to ATRA therapy.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
7/37. Chronic active Epstein-Barr virus infection in an adult.We report a rare adult case of chronic active Epstein-Barr virus (EBV) infection. A 54-year-old woman was admitted to our hospital with intermittent fever, weight loss, hepatosplenomegaly, pancytopenia and liver disturbance. In serological tests for EBV, anti-virus capsid antigen (VCA)-IgG antibody and anti-early antigen (EA)-IgG antibody were markedly elevated and anti-EBV nuclear antigen (EBNA) antibody was negative. EBV genome was detected in the bone marrow nucleated cells and peripheral lymphocytes by Southern blot hybridization. The patient developed left facial edema, bilateral breast tumor and pneumonia. She died one year after admission in spite of the administration of prednisolone, interferon and acyclovir.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
8/37. Cytogenetic findings in a breast stromal sarcoma. Application of fluorescence in situ hybridization to characterize the breakpoint regions in an 11;19 translocation.cytogenetic analysis of a stromal breast sarcoma revealed a complex karyotype that included a reciprocal 11;19 translocation, along with multiple numerical changes, deletions, and other unbalanced structural rearrangements. Karyotypic abnormalities have not been reported previously in this rare neoplasm that arises from mesenchymal breast tissue, and the t(11;19) is of interest because various types of sarcoma are characterized by specific reciprocal translocations. Because of the pericentric nature of the breakpoints on chromosomes 11 and 19 in the t(11;19), classical cytogenetic banding could not reveal the centromeric origin of the translocation derivatives. Using nonisotopic in situ hybridization with chromosome 11 and 19 alpha-satellite probes, the centromere of each derivative chromosome was determined, and the rearrangement was interpreted as a balanced translocation, t(11;19)(q12 or q13.1;p12 or p13.1). This abnormality has not been described previously in any breast tumor.- - - - - - - - - - ranking = 5keywords = hybridization (Clic here for more details about this article) |
9/37. Cytogenetic and comparative genomic hybridization findings in four cases of breast cancer after neoadjuvant chemotherapy.To assess a potential common pattern of genetic alterations in chemotherapy-resistant tumors we analyzed four tumors from breast cancer patients (patients 1-4) after neoadjuvant chemotherapy, by comparative genome hybridization (CGH) and conventional chromosome banding analysis. All patients showed structural aberrations involving chromosomes 1, 5, 11, 16, and 17. In CGH analysis, the patients showed typical imbalances for ductal breast cancer: gains of 1q (3 patients), 5q (2 patients), 8q (3 patients), and X (4 patients) and losses of 1p33 approximately p36 (3 patients), 16q (3 patients), 17p (3 patients), 19 (4 patients), and 22q (4 patients). Other recurrent imbalances of atypical pattern for ductal breast cancer were gain of 4q21 approximately q32 (2 patients), 20q21 approximately q22 (2 patients), and 21 (2 patients) and loss of 20p (3 patients). Three patients showed involvement of several regions bearing genes of drug resistance (MDR1 [HUGO symbol: ABCB1], BCRP [HUGO symbol: ABCG2], MRP1 [HUGO symbol: ABCC1], RFC1); the fourth patient displayed an amplification in the region of MYC (alias c-myc), thus providing--at the level of the light microscope--an explanatory background for the ability of their tumors to survive anthracycline-, taxane- and cyclophosphamide-based chemotherapy. Conventional cytogenetic analysis and CGH displayed highly coincidental findings in the tumors of four patients after neoadjuvant chemotherapy for breast cancer.- - - - - - - - - - ranking = 5keywords = hybridization (Clic here for more details about this article) |
10/37. A case of metastatic breast cancer with outgrowth of HER2-negative cells after eradication of HER2-positive cells by humanized anti-HER2 monoclonal antibody (trastuzumab) combined with docetaxel.A 38-year-old woman with cancer of the left breast underwent a modified radical mastectomy with lymph node dissection. Twenty-one months later, massive liver metastases and pleural carcinomatosis occurred. The liver metastases responded completely to chemotherapy with trastuzumab combined with docetaxel, but the pleural carcinomatosis was refractory to the therapy. fluorescence in situ hybridization showed that both the primary tumor and the metastatic tumors of the lymph nodes were composed of HER2 amplification-positive and HER2 amplification-negative cancer cells. This analysis also detected a single cell with HER2 amplification in the pleural effusion that was taken at the completion of the chemotherapy, but four follow-up tests showed no amplified cells. It is speculated that in the liver metastases, the trastuzumab was cytotoxic to both HER2-amplified and nonamplified cancer cells and may have acted through its antiangiogenic effect. However, in the pleural effusion, the effect of trastuzumab was more specific to HER2-amplified cells and caused outgrowth of cancer cells lacking expression of HER2 receptors.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
| | Next -> |