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Biomedical subjects

E Raymond

Publications and source records attributed to E Raymond.

At least 55 records · Page 3Linked to original sources
PubMed2000

Epidermal growth factor receptor tyrosine kinase as a target for anticancer therapy.

Increasing knowledge of the structure and function of the epidermal growth factor receptor (EGFR) subfamily of tyrosine kinases and of their role in the initiation and progression of various cancers has, in recent years, provided the impetus for a substantial research effort aimed at developing new anticancer therapies that target specific components of the EGFR signal transduction pathway. Selective compounds have been developed that target either the extracellular ligand-binding region of the EGFR or the intracellular tyrosine kinase region, resulting in interference with the signalling pathways that modulate mitogenic and other cancer-promoting responses (e.g. cell motility, cell adhesion, invasion and angiogenesis). Potential new anticancer agents that target the extracellular ligand-binding region of the receptor include a number of monoclonal antibodies, immunotoxins and ligand-binding cytotoxic agents. Agents that target the intracellular tyrosine kinase region include small molecule tyrosine kinase inhibitors (TKIs), which act by interfering with ATP binding to the receptor, and various other compounds that act at substrate-binding regions or downstream components of the signalling pathway. Currently, the most advanced of the newer therapies undergoing clinical development are antireceptor monoclonal antibodies (e.g. trastuzumab and cetuximab) and a number of small molecule EGFR-TKIs principally of the quinazoline and pyrazolo-pyrrolo-pyridopyrimidine inhibitor structural classes. The latter group of compounds offers several advantages in cancer chemotherapy, including the possibility of inhibiting specific deregulated pathways in cancer cells while having minimal effects on normal cell function. They also have favourable pharmacokinetic and pharmacodynamic properties and low toxicity, and some TKIs such as the reversible inhibitor ZD1839 ('Iressa') are now undergoing phase II to III clinical trials. In addition, the accumulation of evidence from laboratory studies strongly suggests that EGFR-selective TKIs will have synergistic effects with other antitumour agents or therapy such as cytostatic agents, conventional cytotoxic drugs and radiotherapy. As our knowledge of signal transduction pathways in cancer increases, it is hoped that further advances in this area will allow the therapeutic potential of these compounds as anticancer agents to be realised.

Antineoplastic Agents↗
PubMed2000

Metabolism of irinotecan (CPT-11) by CYP3A4 and CYP3A5 in humans.

7-Ethyl-10[4-(1-piperidino)-1-piperidino] carbonyloxy-camptothecin (CPT-11), a DNA topoisomerase I inhibitor, undergoes several metabolic pathways to generate conjugated and unconjugated derivatives that could be excreted from the body. The objective of this study was to determine the oxidative metabolites of CPT-11 recovered in human urine samples and to identify cytochrome P450 (CYP) involved in their formation. In addition to the already known metabolites of CPT-11 [SN-38, SN-38-G, 7-ethyl-10-[4-N-(5-aminopentanoic acid)-1-piperidino]carbonyloxycamptothecin (APC), and 7-ethyl-10-(4-amino-1-piperidino) carbonyloxycamptothecin (NPC)], we isolated three oxidized metabolites from the urine of two children and two adults given CPT-11. M1 and M2 (molecular weight, 602) were hydroxylated, respectively, on the CPT moiety and on the terminal piperidine ring of CPT-11. M3 had a molecular mass of 602, but its urine concentration in patients was too low to establish its chemical structure by liquid chromatography/mass spectrometry. In vitro incubations with cells expressing CYP2C8, CYP2C9, CYP1A1, CYP1A2, or CYP3A7 did not produce any detectable metabolites. Only CYP3A4 produced both APC and NPC, resulting from the oxidation of the piperidinylpiperidine side chain of CPT-11 along with metabolite M2. The metabolism of CPT-11 by CYP3A5 was markedly different because neither APC or NPC nor M2 was produced, whereas only one new metabolite, M4 (molecular weight, 558), was generated by de-ethylation of the CPT moiety. No previous study has reported the presence of the M4 metabolite. Production of APC, NPC, M2, and M4 was prevented by ketoconazole, a specific CYP3A inhibitor. The parameters of CPT-11 biotransformation into M2 and M4 were examined using cell lines expressing, respectively, with CYP3A4 and CYP3A5, indicating that CPT-11 is preferentially metabolized by CYP3A4. In conclusion, CYP3A plays a major role in the metabolism of CPT-11, with some differences of the metabolic profile exhibited by 3A4 and 3A5.

Adolescent↗
PubMed2000

[Epidermoid carcinoma of the head and neck: contribution of chemotherapy in case of recurrence and locally advanced disease. Review of the literature].

Epidermoid carcinoma of the head and neck accounts for 10% of all cancers. At diagnosis, 60% of patients have a locally advanced disease, leading to high mortality and major functional handicaps. Chemotherapy has been shown to be active in patients presenting metastatic and/or locoregional recurrence, with 20 to 30% response rates, although no clearly established survival benefit has been demonstrated. Combining chemotherapy with surgery and/or radiotherapy has become possible with the development of new drugs and has recently led to major changes in management protocols for locally advanced epidermoid carcinoma of the head and neck. Therapeutic gain has been focalized on improving locoregional control, decreasing metastatic spread, and on the concept of an organ conservation strategy with schedules including chemotherapy as an inducing, concomitant, or alternating treatment with radiotherapy. Although many agents have demonstrated their efficacy, the role of chemotherapy in epidermoid carcinoma of the head and neck is not totally defined. The aim of treatment in metastatic and/or locoregional recurrent disease is palliative care. Regimens associating cisplatinum give a high response rate in patients previously untreated, without any real benefit in terms of survival. An evaluation of the activity of new agents with novel modes of action is currently under way. In locally advanced disease, concomitant chemotherapy with radiotherapy seems to give a minimal but real benefit as evidenced in the different meta-analyses recently published.

Carcinoma, Squamous Cell↗
PubMed2000

[Zd 1839 "Iressa"].

ZD 1839 is a highly specific EGF receptor tyrosine kinase inhibitor. Inhibition of EGF receptor transphosphorylation by ZD 1839 blocks the signal transduction at the first step, thus providing antiproliferative effects. Preclinical studies demonstrated efficacy and good bioavailability. The terminal half-life of the compound in patients is ranging from 27 to 41 hours, allowing single oral dosing. Tolerance in healthy volunteers was excellent. In phase I studies, toxicity was manageable. Most common side effects were skin rash, nausea, vomiting, and diarrhea. During those studies, clinical responses were observed in patients with various malignant tumors, in particular non small cell lung cancer. Phase II and III studies are ongoing.

Administration, Oral↗
PubMed1999

Prostacyclin and thromboxane changes predating clinical onset of preeclampsia: a multicenter prospective study.

CONTEXT: An imbalance in vasodilating (prostacyclin [PGI2]) and vasoconstricting (thromboxane A2 [TxA2]) eicosanoids may be important in preeclampsia, but prospective data from large studies needed to resolve this issue are lacking. Because most trials using aspirin to reduce TxA2 production have failed to prevent preeclampsia, it is critical to determine whether eicosanoid changes occur before the onset of clinical disease or are secondary to clinical manifestations of preeclampsia. OBJECTIVE: To determine whether PGI2 or TxA2 changes occur before onset of clinical signs of preeclampsia. DESIGN, SETTING, AND PARTICIPANTS: Multicenter prospective study from 1992 to 1995 of subjects from the placebo arm of the Calcium for Preeclampsia Prevention Trial. Women who developed preeclampsia (n = 134) were compared with matched normotensive control women (n = 139). MAIN OUTCOME MEASURES: Excretion of urinary metabolites of PGI2 (PGI-M) and TxA2 (Tx-M) as measured from timed urine collections obtained prospectively before 22 weeks', between 26 and 29 weeks', and at 36 weeks' gestation. RESULTS: Women who developed preeclampsia had significantly lower PGI-M levels throughout pregnancy, even at 13 to 16 weeks' gestation (long before the onset of clinical disease); their gestational age-adjusted levels were 17% lower than those of controls (95% confidence interval [CI], 6%-27%; P=.005). The Tx-M levels of preeclamptic women were not significantly higher overall (9% higher than those of controls; 95% CI, -3% to 23%; P=.14). The ratio of Tx-M to PGI-M, used to express relative vasoconstricting vs vasodilating effects, was 24% higher (95% CI, 6%-45%) in preeclamptic women throughout pregnancy (P=.007). CONCLUSIONS: Our results show that reduced PGI2 production, but not increased TxA2 production, occurs many months before clinical onset of preeclampsia. Aspirin trials may have failed because an increase in thromboxane production is not the initial anomaly. Future interventions should make correcting prostacyclin deficiency a major part of the strategy to balance the abnormal vasoconstrictor-vasodilator ratio present in preeclampsia.

6-Ketoprostaglandin F1 alpha↗
PubMed1999

Effects of cationic porphyrins as G-quadruplex interactive agents in human tumor cells.

A series of cationic porphyrins has been identified as G-quadruplex interactive agents (QIAs) that stabilize telomeric G-quadruplex DNA and thereby inhibit human telomerase; 50% inhibition of telomerase activity was achieved in HeLa cell-free extract at porphyrin concentrations in the range < or = 50 microM. Cytotoxicity of the porphyrins in vitro was assessed in normal human cells (fibroblast and breast) and human tumor cells representing models selected for high telomerase activity and short telomeres (breast carcinoma, prostate, and lymphoma). In general, the cytotoxicity (EC50, effective concentration for 50% inhibition of cell proliferation) against normal and tumor cells was > 50 microM. The porphyrins were readily absorbed into tumor cell nuclei in culture. Inhibition of telomerase activity in MCF7 cells by subcytotoxic concentrations of TMPyP4 showed time and concentration dependence at 1-100 microM TMPyP4 over 15 days in culture (10 population doubling times). The inhibition of telomerase activity was paralleled by a cell growth arrest in G2-M. These results suggest that relevant biological effects of porphyrins can be achieved at concentrations that do not have general cytotoxic effects on cells. Moreover, the data support the concept that a rational, structure-based approach is possible to design novel telomere-interactive agents with application to a selective and specific anticancer therapy.

Antineoplastic Agents↗
PubMed1999

Supraadditive effect of 2',2'-difluorodeoxycytidine (gemcitabine) in combination with oxaliplatin in human cancer cell lines.

PURPOSE: This study assessed the cytotoxic effects of the nucleoside analog gemcitabine in combination with the diaminocyclohexane platinum compound oxaliplatin. METHODS: Growth inhibition studies were performed using the human CEM leukemia cell line and the colon-cancer cell lines HCT 116 and Colo 320 DM. Gemcitabine-oxaliplatin combinations were compared with gemcitabine-cisplatin combinations in the same cell lines using similar experimental settings. Cells were exposed for 2 h to gemcitabine and then for 24 h to oxaliplatin or cisplatin, and vice versa. RESULTS: The 50% inhibitory concentrations (IC50 values) in single-drug experiments using 2 h of exposure to gemcitabine and 24 h of exposure to oxaliplatin or cisplatin were, respectively, 89 pM, 11.1 microM, and 10.3 microM for CEM cells; 46 pM, 10.2 microM, and 2.7 microM for HCT 116 cells; and 102 pM, 4.6 microM, and 8.6 microM for Colo 320 DM cells. Gemcitabine-oxaliplatin combinations displayed supraadditive effects in human leukemia and colon-cancer cell lines. The sequence of gemcitabine followed by oxaliplatin was more effective than the opposite sequence in HCT 116 and Colo 320 DM colon-cancer cell lines, whereas the sequence of oxaliplatin followed by gemcitabine yielded to synergistic effects in CEM cells. The cytotoxic effects of gemcitabine-oxaliplatin combinations were better than (HCT 116 cells) or equal to (CEM and Colo 320 DM cells) those of gemcitabine-cisplatin combinations. CONCLUSION: Our data show that the combination of gemcitabine with oxaliplatin exerts potent antiproliferative effects in human leukemia and colon cancer cells, warranting further investigations in the framework of phase I-II trials as an alternative for the treatment of solid malignancies.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Acceptability of two spermicides in five countries.

Data from a large, international, multicenter, randomized trial were analyzed to compare the acceptability of two nonoxynol-9 spermicide preparations. Women who wished to use a spermicide for contraception were randomly assigned to use either a foaming tablet (n = 383) or a nonoxynol-9 film (n = 382) for 28 weeks as their only method of contraception. Participants completed questionnaires about acceptability of the assigned product 4 weeks after admission and at discontinuation. Women in both groups had very favorable opinions of the spermicide. The proportion of women who said that they liked their assigned product very much was 50% in the tablet group and 55% in the film group. Significantly more women in the film group rated the spermicide difficult to insert and stated that the product stuck to the finger during insertion. More women in the tablet group said that the product was messy and that, at least once, it did not dissolve. In both groups, liking the product was significantly associated with consistency of use, but not with subsequent pregnancy. Participants' male partners had little influence on participants' opinions about, or use of, the spermicides. Although previous analyses showed that both spermicides are associated with high pregnancy rates, they are both highly acceptable to most women.

Adolescent↗
PubMed1999

Influence of cycle variability and coital frequency on the risk of pregnancy.

Researchers have cautioned against generalizing results from contraceptive trials because these studies rely on self-selected participants meeting strict selection criteria who may differ from typical users. Using information collected on daily diaries, we reanalyzed data from the recently completed Reality female condom clinical trial to evaluate factors that influence the probability of pregnancy. Noncompliant women, women with less variable menstrual cycles (17-43 days), and women engaging in intercourse frequently (> or = 11 acts per month) were more likely to conceive during this 6-month trial. The adjusted hazard ratios and 95% confidence intervals for these three covariates were 6.1 (2.0-18.7), 7.2 (1.0-54.3), and 2.0 (0.7-5.3), respectively. The strict selection criteria used in this study failed to recruit a homogeneous cohort with respect to factors that influence the risk of pregnancy. The overall pregnancy rate does not pertain to individual study participants, but rather represent average effects for a population with the particular mix of characteristics found in this study. In particular, we not only confirm the well known importance of compliance and the obvious role of frequency of intercourse, but also demonstrate that women with cycles outside the range of 17-43 days appear to be at a much lower risk of pregnancy.

Adolescent↗
PubMed1999

Contraceptive effectiveness of two spermicides: a randomized trial.

OBJECTIVE: We conducted a multinational randomized trial to determine whether a spermicidal film containing 72 mg of nonoxynol-9 per film was at least as effective in preventing pregnancy as a foaming tablet containing 100 mg of nonoxynol-9 per tablet. METHODS: Between September 1995 and July 1997, 765 women aged 18-35 years who had no evidence of subfecundity were randomly assigned to use one of the two spermicides as their only contraceptive method at every coital act for 28 weeks. Participants were asked to keep coital diaries throughout the study period. Pregnancy tests were performed on a scheduled basis. Each participant was followed for 28 weeks or until she stopped considering the spermicide as her primary method of contraception. RESULTS: The Kaplan-Meier estimate of the 6-month probability of pregnancy during typical use of the spermicide was 28.0% in the tablet group and 24.9% in the film group (P = .78, one-tailed test). The study had nearly 75% power to have detected a difference of seven percentage points between groups. Results were almost identical when the analysis included only months when the participants reported use of the spermicide during every coital act. Reported levels of sexual activity and compliance with use of the spermicide were high in both groups. CONCLUSION: The contraceptive effectiveness of these two spermicidal products appeared similar. Both products were associated with a fairly high risk of pregnancy in this young, highly sexually active population.

Adolescent↗
PubMed1999

Phase II trial combining mitomycin with 5-fluorouracil, epirubicin, and cisplatin in recurrent and metastatic undifferentiated carcinoma of nasopharyngeal type.

BACKGROUND: This phase-II study was conducted to investigate the potential benefit from the addition of mitomycin to a conventional anthracycline-cisplatin- and 5-fluorouracil-based chemotherapy for recurrent and metastatic undifferentiated carcinoma of nasopharyngeal type (UCNT). PATIENTS AND METHODS: Between July 1989 and December 1991, 44 consecutive patients (M/F 36/8; median age: 45, range 20-72; performance status (PS) 0: 20 patients, PS 1: 14 patients, PS 2: 10 patients) with recurrent or metastatic UCNT were entered in this study after complete clinical, biological, and radiological pre-therapeutic work-ups. Chemotherapy (FMEP regimen) consisted of 800 mg/m2/day 5-fluorouracil in continuous infusion from day 1 to day 4 combined with 70 mg/m2 epirubicin, 10 mg/m2 mitomycin, and 100 mg/m2 cisplatin on day 1, every four weeks for six cycles. Mitomycin was delivered in cycles 1, 3, and 5 only. Eleven patients had isolated loco-regional recurrences, 12 patients had local recurrences associated with distant metastasis, and 21 patients had metastasis only. Toxicity and response were evaluated according to WHO criteria. TOXICITY: Grade 3-4 neutropenia was observed in 122 of 212 evaluable cycles (57%) and 39 of 44 patients (89%); febrile neutropenia occurred in 16 patients (36%) and 24 cycles (11.3%). Grade 3-4 thrombocytopenia was observed in 27 patients (61%) and 45 cycles (21%), including 27 of 45 cycles (60%) with mitomycin. Grade 3 anemia was noted in 18 patients (40%) and 23 cycles (11%), including 18 of 23 cycles (78%) with mitomycin. Grade 3-4 mucositis occurred in 25 cycles (11%) and 14 patients (32%), mainly in those previously treated with radiation therapy in the head and neck area. There were four treatment-related deaths (9%); three of them neutropenia-related, and one of cardiac toxicity. RESPONSE: Forty-four patients were evaluable for response: There were 23 of 44 objective responses (52%), including six complete responses (13%), and 17 partial responses (38%). Additional radiotherapy was given to 13 patients after documentation of response: Nasopharyngeal tumor + cervical nodes (eight patients) and/or on bone metastasis sites (five patients); mediastinal lymph nodes (one patient). At a median follow-up of 87 months (range 71-100), five patients are alive and in continuous complete remission. The median survival time was 14 months and the median time to progression nine months. CONCLUSION: The regimen under study is active in recurrent/metastatic UCNT, but associated with excessive toxicity.

Adult↗
PubMed1999

A human breast cancer model for the study of telomerase inhibitors based on a new biotinylated-primer extension assay.

Telomerase is an RNA-dependent polymerase that synthesizes telomeric DNA (TTAGGG)n repeats. The overall goal of our work was to establish human cancer models that can be used to design clinical trials with telomerase inhibitors. The objectives of this study were (1) to set up a human breast cancer system that allows evaluation of the effects of telomerase inhibitors in cultured cells using a non-amplified telomerase assay and (2) to test this system using two drugs (cisplatin and TMPyP4) that affect the telomerase expression in breast cancer cells in culture. We first compared the telomerase activity in a variety of human breast cancer cell lines to that of other tumour types using a new biotinylated-primer extension assay. Our method, based on a non-amplified primer extension assay shows the direct incorporation of 32P-labelled nucleotides induced by telomerase on human telomeric primers. The 32P-dGTP labelled telomerase-extended 5'-biotinylated (TTAGGG)3 primer can subsequently be separated using streptavidin-coated magnetic beads. As compared to other non-amplified method, we showed that this procedure improved the characterization and the quantification of the banding pattern resulting from telomerase extension by reducing the radioactive background. Using this method, we observed that telomerase activity varies markedly in a panel of 39 human cancer cell lines. For example, MCF7 breast cancer cells in culture showed intermediate telomerase activity corresponding to 33.8+/-3.4% of that of the HeLa cells (reference cell line). Similarly, the telomere length varied with each cell line (average: 6.24+/-6.16). No correlation between the level of telomerase and telomere length was observed, suggesting that a high processivity is not required to maintain telomeres and that, in some cell lines, another mechanism of telomere elongation can maintain telomere length. From this study, we selected MCF7 and MX1 models that showed reproducible telomerase activity and a relatively limited telomere length for the testing of potential telomere-telomerase interacting agents. Using cisplatin and a new porphyrin-derived compound TMPyP4, we showed that our model was able to detect a down-regulation of the telomerase activity in MCF7 cells in culture and in a human MX1 tumour xenografts. Based on these results, a breast cancer model for evaluating telomerase and telomere interactive agents is proposed.

Animals↗
PubMed1999

Recombinant human interleukin-11 is unlikely to stimulate the growth of the most common solid tumors.

Recombinant human interleukin-11 (rhIL-11) has been shown to enhance recovery from thrombocytopenia and mucosal injury after cancer chemotherapy. Since RNA for the receptor and signal transducer for IL-11 is detected in many cell types including some cancer cells, it was theoretically possible that rhIL-11 could affect the growth of tumor cells. This study was intended to determine whether rhIL-11 stimulates the proliferation of human tumor colony-forming units (TCFUs) taken directly from patients. Tumor cells were cultured in soft agar and continuously exposed to three concentrations of rhIL-11 (1.0, 10.0 and 100.0 U/ml) for 14 days in the capillary cloning system. Growth stimulation was noted in two of 66 (3%) of evaluable specimens, including one of 14 evaluable non-small cell lung cancer and one of five evaluable colon cancer specimens. In these two specimens, there was no increased stimulation of TCFUs with escalating concentrations of rhIL-11. Interestingly, the highest concentration of rhIL-11 tested inhibited the growth of 16 specimens (24.2%; 95% confidence interval 13.9-34.5%). Growth inhibition demonstrated a concentration-response relationship (p < 0.001). These results suggest that rhIL-11 appears unlikely to stimulate the growth of the most common solid tumors.

Antineoplastic Agents↗
PubMed1999

A risk-benefit assessment of amifostine in cytoprotection.

Recent advances in chemotherapy have focused on the benefit of high dose regimens, increasing the dose intensity of conventional chemotherapy and using intensified chemotherapy with or without autologous bone marrow rescue. Dose intensity usually increases objective response rates of antineoplastic drugs and might, in some circumstances, improves survival. However, unacceptable acute and/or cumulative toxicity often impairs the proper management of patients, leading to dose reduction or treatment delay, thus reducing the efficacy and potentially the quality of life of patients. Therefore, considerable efforts have been made to manage, to prevent, and to delay many acute and cumulative treatment-related toxicities. Amifostine (WR-2721 ) is a multiorgan cytoprotector which has demonstrated cytoprotective effects, in vitro and in vivo, against the most common cytotoxic drug-related toxicities and against radiation-induced adverse effects in healthy tissues. In vitro and in vivo, cytoprotection was observed in several organs including kidney, haematopoietic stem cells, myocardial cells, neural cells, and mucosa, without detectable protection of malignant cells. In addition, in preclinical studies, amifostine appeared to be able to reduce the risk of radiation-induced secondary neoplasms. Phase I studies showed that nausea/vomiting and hypotension are the dose-limiting toxicities of amifostine and these may be controlled by reducing the duration of injection of amifostine. Phase II and randomised studies have confirmed the efficacy of amifostine in protecting against radiotherapy-induced mucositis, cisplatin-induced nephrotoxicity, cyclophosphamide-induced neutropenia and carboplatin-induced thrombocytopenia. Importantly, the cytoprotection of healthy tissues occurred without any significant deleterious effect on response rate, time to progression, and survival of patients receiving amifostine. However, in addition to the potential quality of life benefit, the most important question of whether the use of a cytoprotective agent might translate into the possibility of maintaining the dose intensity of anticancer therapies has still to be answered. The real benefit of amifostine in the overall management of patients with cancer requires additional studies to determine whether this chemoprotective approach can be of benefit to patients by increasing response rate, time to progression, and long term survival in patients receiving the more recent combination therapies involving new drugs such as the taxanes and oxaliplatin.

Amifostine↗
PubMed1999

Molecular detection of telomerase-positive circulating epithelial cells in metastatic breast cancer patients.

The detection of circulating tumor cells and micrometastases may have important therapeutic and prognostic implications. Telomerase is a hallmark of cancer and is absent from normal epithelial cells. The aim of this study was to use telomerase activity as a molecular marker for the detection of cancer cells in blood of patients with breast cancer. Blood samples were collected from 25 women with stage IV breast cancer and 9 healthy volunteers. Peripheral blood mononuclear cells were isolated by using Ficoll/Hypaque. Immunomagnetic beads coated with an epithelial-specific antibody (BerEP4) were used to harvest epithelial cells from peripheral blood mononuclear cells. Telomerase activity was detected in harvested epithelial cells (HECs) using two different telomerase-PCR-ELISA methods. HECs from blood samples of 21 of 25 (84%) patients with breast cancer were telomerase positive. Telomerase activity was undetectable in HECs from the nine healthy volunteers, demonstrating the specificity of the association between telomerase activity in HECs and stage IV breast cancer. Thus, determination of telomerase activity in HECs appears to be a sensitive, specific, and noninvasive approach for detecting circulating epithelial cancer cells in patients with metastatic breast cancer. This method could be of great value in monitoring the cancer cell proliferation during chemotherapy. This study should be now extended to patients with early-stage breast cancer to investigate the role of telomerase expression by HECs and to evaluate its prognostic value.

Adult↗