Search

We report four cases of mixed mu¨llerian tumors of the endometrium arising in postmenopausal women taking tamoxifen for breast carcinoma. Various histopathologic features were encountered: one mu¨llerian adenosarcoma and three malignant mixed mu¨llerian tumors so called carcinosarcomas (in one case the sarcomatous component was homologous composed of tissues normally found in the uterus, while the others were heterologous because they were containing some elements normally not found in the uterus). Concern has been raised about prolonged tamoxifen treatment and subsequent occurrence of endometrial adenocarcinoma.  Then, attention has been drawn through high-risk histologic subtypes including poorly differentiated patterns, uterine sarcomas and such mixed mu¨llerian tumors. There is no consensus regarding internal surveillance of women receiving tamoxifen. The usefulness of pelvic sonography has not been demonstrated. [Copyright &y& Elsevier]

Tumour growth is associated with modifications to the structure of glycan residues belonging to the glycoproteins and glycolipids present at the cell surface. These aberrant glycosylations, arising from dysfunction of glycosyltransferases and (or) glycosidases, most often result in a shortening of the glycan chains or an over-expression of structures on the cells that are normally absent or discrete. Some of these changes, such as the expression of antigen Tn in cancers of the breast or colon, appear very early in the evolution of the disease, and can indeed be found in pathologies that are generally considered benign. Most of the cell proteins are glycosylated, including the molecules involved in inter-cell recognition, attachment, cell cycle regulation and apoptosis. The consequences of these disturbances therefore affect many aspects of the biology of the cell and its fate in the body. The impact is particularly evident when the glycan moiety contributes to the functional site of the molecule, the activity of which is then modified or abolished. In addition, the expression of functional residues recognised by molecules with lectin activity, normally restricted to phagocyte cells, is liable to promote metastasis formation by favouring the crossing of the vascular endothelium by tumour cells The identification, using plant lectins and monoclonal antibodies, of oligosaccharides associated with tumour formation, is relevant for both diagnosis, as some glycotopes are expressed before any other cellular anomaly, and prognosis, since certain sequences, e.g., that recognised by L-PHA, reflect dysfunction in the glycan synthesis, culminating in the formation of terminal oside structures that favour the metastatic spread of tumour cells. Therapeutic applications can also be envisaged through action on the tumour glycan antigens by means of naturally-occurring or synthetic immunising entities, or through the use of analogues of sugars that block the activities of the glycosyltransferases or glycosidases responsible for the synthesis of potentially dangerous glycotopes. Beside their practical use, the expression of tumour glycan antigens raises the question of their role in directing the cell towards cancer formation., (Copyright John Libbey Eurotext 2003.)

Induction chemotherapy provides an excellent model for evaluation of potential predictive factors. We studied expression of SBR grade, estrogen (ER) and progesterone (PR) receptors, HER2, Ki67 and P53 on core biopsies before and after chemotherapy in a series of 115 patients, who received anthracycline-based induction chemotherapy for primary breast cancer. HER2 overexpression independently predicted response to neoadjuvant anthracycline-based chemotherapy. Patients with HER2-positive status are 4.54 times more likely to have a pathological complete response than those with negative status (p<0.005). HER2, ER and PR status were stable during treatment. P53 and Ki67 significantly increased after treatment (p<0.005 and p<0.0005). SBR grade, proliferation markers, ER evaluated before and after treatment predicted disease-free survival (DFS) in univariate analysis.

O(6)-methylguanine-DNA methyl transferase (MGMT) in human carcinomas has been associated with tumor resistance to alkylating agents. The aims of this study were: i) to correlate tumor MGMT expression and patient and tumor characteristics in malignant breast carcinomas treated with induction chemotherapy including cyclophosphamide (CPM) and ii) to study the predictive and prognostic values of tumor MGMT gene expression. We used RT-PCR to measure the levels of tumor MGMT expression in 107 patients with breast carcinomas prior to neoadjuvant chemotherapy. Sixty patients (56%) received anthracyclines and CPM and 47 (44%) received only anthracyclines. Low levels of MGMT expression correlated with Scarff-Bloom-Richardson grade III (p<0.005), elevated S-phase (p<0.05), negative estrogen receptors (p<0.05), metastatic status (p<0.05) and occurrence of death (p=0.01). MGMT expression was not predictive of treatment response. Unexpectedly, survival was longer when tumor MGMT expression was high (p<0.005). The 4-year survival rate was 76% for high level MGMT patients and only 55% for others. This difference is also significant using the COX model (p<0.05). In breast cancer, tumor MGMT expression was not predictive of response to CPM. A low MGMT expression was significantly related to poor survival.

Background: BRCA1 and BRCA2 are breast cancer susceptibility genes. Recent studies suggest that BRCA1 interacts with a great variety of proteins, including BRCA2, cell-cycle regulators, transcriptional activators and repressors. We investigated the expression of both BRCA1 and BRCA2 during the progression of the cell cycle of human tumor cell lines from different origins (MCF7, MDA-MB231, PA1 and CCL221) in two growth status (60% and 100% of confluency)., Methods: First, the growth status was characterized by determination of the cell cycle by flow cytometry analysis. At the same time, immunohistochemistry was performed to follow BRCA1 and BRCA2 protein expression and then, quantification of BRCA1 and BRCA2 transcripts was realized using real-time quantitative RT-PCR., Results: We reported in studied tumor cell lines with 60% of confluency by comparison with 100% of confluency, an increase in the BRCA1 and BRCA2 expression at the level of proteins and transcripts., Conclusion: Therefore, the expression of both BRCA1 and BRCA2 genes at the protein and mRNA levels appear to be up-regulated after cell proliferation in human tumor cell lines from different origins.

N'-[2-chloroethyl]-N[2-(methylsulfonyl) ethyl]-N'-nitrosourea (cystemustine),a chloroethylnitrosourea antineoplastic drug, provokes cellular proliferation inhibition and redifferentiation, but there was no cell death in B16 melanoma tumors. Because the phospholipid (Plp) metabolism is tightly involved in tumor growth regulation and tumor cell survival, we tested the hypothesis that melanoma tumors undergo adaptive Plp metabolism changes to survive treatment. Measurements of Plp derivatives were performed using a novel proton nuclear magnetic resonance Spectroscopy application using magic angle spinning on intact tumor tissue samples. Phosphatidylcholine levels were obtained from one-dimensional spectra, and relative levels of choline- and ethanolamine-containing compounds were derived from two-dimensional spectra (total correlation spectroscopy sequence). Two major findings emerged from this study: (a) during tumor growth inhibition, there was a transient accumulation of choline, glycerophosphocholine, and glycerophosphoethanolamine and a sustained increase in phosphocholine and phosphoethanolamine, whereas phosphatidylcholine levels remained unchanged; and (b) during tumor growth recovery, only phosphocholine and phosphoethanolamine remained elevated. Therefore, cystemustine-treated B16 melanoma tumors acquire a new Plp metabolism phenotype, a mechanism that could participate in tumor cell redifferentiation and/or survival.

Purpose: In order to improve the breast conservation rate for noninflammatory operable breast cancer stage II and IIIa, neoadjuvant chemotherapy containing vinorelbine, 25 mg/m(2), epirubicin, 35 mg/m(2), and methotrexate, 20 mg/m(2), VEM, was administered days 1 and 8 every 28 days for six cycles., Methods: From October, 1991 to April, 1996, 89 patients (median age 52 years, range 31-72; 68 stage II and 19 stage IIIa) received 519 cycles (median six) of VEM chemotherapy., Results: Hematotoxicity was mild (World Health Organization grade 3-4 neutropenia in 28% of cycles for 22 patients, and anemia or thrombocytopenia >grade 2) when it occurred, and there were no toxic deaths. The clinical objective response was 90% (28% complete response and 62% partial response). All patients underwent surgery: 77 (87%) had conservative and 12 (13%) had modified radical mastectomy, and 12 (14%) reached pathological complete response. At December, 2000, with a median follow-up of 86 months (39-100), 13 patients had relapsed, and five had died of metastatic disease. Median disease-free survival was 100 months (8.4 years) and median survival had not yet been reached.

Introduction: Tamoxifen--a non steroidal triphenylethyl compound--in addition to having antiestrogenic properties may provoke weak estrogenic effects, the well known "paradoxical effects" on the female genital tractus. Concern has been raised about prolonged tamoxifen treatment and subsequent occurrence of endometrial adenocarcinoma; subsequent attention has been drawn through high risk histologic subtypes including poorly differentiated patterns and uterine sarcomas., Exegesis: We report two cases of uterine sarcoma arising in postmenopausal women taking tamoxifen, 20 mg daily during 38 and 42 months, for breast carcinoma: one leiomyosarcoma and one endometrial stromal sarcoma; both cases were asymptomatic and detected by pelvic sonography., Conclusion: Further studies will be required to establish if there is a relationship between long term tamoxifen exposure and highly aggressive types of cancer of the uterine corpus exhibiting adverse histologic features such as uterine sarcomas. There is no consensus regarding uterine surveillance of women receiving tamoxifen. We advocate an annual gynecologic examination plus imaging by means of transvaginal ultrasonography.

Introduction: Stewart-Treves syndrome has been defined by the eponymous authors as a lymphangiosarcoma in a setting of postmastectomy upper extremity lymphoedema., Exegesis: The clinical record of one patient with Stewart-Treves syndrome is analyzed. The primary angiosarcoma of the skin represented by a purple nodule occurred on a chronic lymphoedematous arm following radical mastectomy and axillary lymph node dissection for breast carcinoma performed 9 years earlier. Immunohistochemistry tests formally eliminated epithelial cutaneous metastasis and produced evidence in favour of conjunctive vascular tissue origin of the tumor., Conclusion: Conservative surgery for breast cancer, application of axillary sentinel node biopsy in the lymphatic staging and prevention of arm lymphoedema should reduce the incidence of this syndrome.

We characterized the expression of BRCA1 and BRCA2 in 38 sporadic colorectal carcinomas and matched normal mucosas with 9 anti-BRCA1 antibodies and 4 anti-BRCA2 antibodies, raised against several different epitopes, using immunohistochemical technique. We demonstrated an increased BRCA1 and BRCA2 staining in the apical cell pole of epithelial malignant cells and we also revealed a significant increase in BRCA1 and BRCA2 nuclear foci in tumor colorectal specimens in comparison with corresponding normal tissues. These increases in BRCA1 and BRCA2 expression may be explained by the fact that colorectal tissue is subject to very active proliferation and differentiation.

N'-(2-Chloroethyl)-N-(2-(methylsulfonyl)-ethyl)-N'-nitrosourea (cystemustine) is a chloroethylnitrosourea that has been used in the treatment of human melanoma. Its main antitumor effect is DNA damage to malignant melanocytes. Although unreported at present, other effects may also account for its cytotoxicity, some of them could be more or less delayed with respect to its administration. In this report, we have developed a model of secondary tumor with B16 melanoma in syngeneic C57B16 recipients to investigate the impact of cystemustine treatment of primary B16 melanoma tumors on the fate of secondary implanted untreated tumors. The data presented in this report indicate that cystemustine-treated cells or the administration of cystemustine provoke an important growth delay of primary melanoma tumors, together with an increase in cell pigmentation and cell morphology changes. Data also show that prime treatment induces a dramatic decrease in tumor weight of secondary untreated tumors accompanied by an increase in melanin content and an alteration of cell morphology. Finally, 1H-NMR spectroscopy was performed on treated B16 cells, showing an alteration in the phospholipid derivatives of melanocytes, suggesting subsequent modifications of membrane phospholipid composition. In conclusion, the data highlight two important findings: (a) cystemustine produces modifications other than DNA damage, i.e., cell morphology changes, pigmentation, and phospholipid metabolism alterations, indicating an interference with cell cycle, cell redifferentiation, and proliferation programs; and (b) cystemustine-treated tumors appear to confer a protective effect against the development of secondary untreated tumors that may be mediated by cytokines or an immune response.

We have analyzed by immunohistochemistry Brca1 and Brca2 protein expression in mouse during embryonic development, in adult tissues, and during postnatal mammary gland development. Our observations confirm previous localization of Brca1 and Brca2 mRNA on frozen sections by in situ hybridization, and demonstrate that Brca1 and Brca2 proteins are expressed in rapidly proliferating cell types undergoing differentiation. These results imply that Brca1 and Brca2 proteins are involved in the process of proliferation and differentiation in multiple tissues, notably in the mammary gland during pregnancy and lactation.

Unlabelled: The aim of this study was to investigate joint scintigraphy in rabbits with 99mTc-N-[3-(triethylammonio)propyl]-15ane-N5 (NTP 15-5), a new radiopharmaceutical that specifically localizes in cartilaginous tissues., Methods: Scans obtained after intravenous injection of the 99mTc-labeled compound in normal and arthropathy-induced rabbits were compared with those of the bone-imaging agent 99mTc-methylene diphosphonate (99mTc-MDP)., Results: The radioactive uptake of 99mTc-NTP 15-5 was detected in cartilaginous tissues 5 min after injection and was stable for 2 h. The uptake intensity was related to age and joint disease severity, and cartilage alterations not revealed by radiography induced a significant decrease of radiotracer uptake. On the other hand, imaging performed with 99mTc-MDP did not reveal the early changes in arthrosis but was more specific for bone remodeling in advanced stages of diseases or in inflammatory processes., Conclusion: Our results indicate that 99mTc-NTP 15-5 could be a good tracer for human arthrosic and arthritic cartilage detection, especially for the early diagnosis of joint diseases.