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O Chinot

Publications and source records attributed to O Chinot.

At least 19 recordsLinked to original sources
PubMed2006

Identification of secondary structure in the 5'-untranslated region of the human adrenomedullin mRNA with implications for the regulation of mRNA translation.

Adrenomedullin (AM) is a multifunctional regulatory peptide with important angiogenic and mitogenic properties. Here we identify a region of stable secondary structure in the 5'-untranslated region (5' UTR) of human AM mRNA. Reverse transcriptase-polymerase chain reaction of the 5' UTR consistently resulted, in addition to the product with the expected size of 155 base pair (bp), in a second product with an approximately 65-bp deletion from the central region of the 5' UTR, suggesting the presence of a secondary structure. The presence of a stem-loop structure was confirmed by probing the 5' UTR with RNases with selectivity for single- or double-stranded RNA. We investigated the role of this stem-loop structure in expression of luciferase reporter gene in cultured cell lines. Reporter assays using a chimeric mRNA that combined luciferase and the 5' UTR of AM mRNA demonstrated a dramatic decrease of the reporter activity owing to a decreased translation, whereas the deletion of the stem-loop structure localized between nt +31 and +95 from the cap site led to the recovery of activity. Gel migration shift assays using cytosolic extracts from mammalian cell lines demonstrate a specific binding of a cytosolic protein to riboprobes containing the 5' UTR of AM but not to riboprobes either corresponding to other areas of the message or containing the 5' UTR but lacking the region of secondary structure. Although we conclude that the 5' UTR of the human AM mRNA can modulate the translation of AM mRNA in vivo, and that the predicted stem-loop structure is necessary for this inhibition, the functional consequences of the cis element-binding activity remain to be determined.

5' Untranslated Regions↗
PubMed2005

The role of Gamma Knife radiosurgery in the treatment of pineal parenchymal tumours.

OBJECT: The aim of this study was to document the possible role of Gamma Knife radiosurgery, suitable for the treatment of deep and well limited tumors, in the management of pineal parenchymal tumors (PPT). POPULATION AND METHODS: We reviewed retrospectively a series of 13 patients with PPT treated by Gamma Knife radiosurgery during 16 procedures. Mean age was 31 (range 10 to 74). Eight patients had pineocytomas (61.5%), and 5 had pineoblastomas (38.5%). Radiosurgery was performed alone in 6 cases, after partial microsurgical resection in 3 cases, in association with chemotherapy in 3 cases and following conventional fractionated radiotherapy in 1 case. The marginal dose to these tumors ranged from 11 to 20 Gy (mean 15 Gy). RESULTS: With a mean follow-up of 34 months (range 6 to 88), all tumors responded to treatment and disappeared or ceased growing. Two patients with pineoblastoma had tumor size progression out of the initial target requiring several radiosurgery procedures. At the end of the follow-up period, 10 out of 12 patients were alive. Two patients with pineoblastoma died because of carcinomatous meningitis or tumor size progression. We observed no mortality or major morbidity related to radiosurgery. CONCLUSION: This study confirms that radiosurgery can be an effective and safe primary treatment modality for patients with pineocytomas. It should have a role in multimodality therapy which includes microsurgical resection, fractionated radiotherapy and chemotherapy for the management of malignant pineal tumors.

Adolescent↗
PubMed2005

Temozolomide in combination with BCNU before and after radiotherapy in patients with inoperable newly diagnosed glioblastoma multiforme.

BACKGROUND: The aim of this study was to evaluate the efficacy and safety of carmustine (BCNU) in combination with temozolomide as first-line chemotherapy before and after radiotherapy (RT) in patients with inoperable, newly diagnosed glioblastoma multiforme (GBM). PATIENTS AND METHODS: Forty patients were treated with BCNU (150 mg/m2) on day 1 and temozolomide (110 mg/m2/day) on days 1 through 5 of each 42-day cycle for up to four cycles prior to conventional RT (2 Gy fractions to a total of 60 Gy). After RT, BCNU + temozolomide was administered for four additional cycles or until progression. The primary end point was response rate; secondary end points included progression-free survival (PFS); overall survival (OS) and safety. RESULTS: Sixty per cent of patients completed four cycles of neo-adjuvant BCNU + temozolomide. Objective response rate (intention-to-treat) was 42.5% (95% confidence interval 27% to 58%), including two (5%) complete and 15 (37.5%) partial responses. In the eligible population (n=37) the objective response rate was 46%. Nine (24%) patients had stable disease and 14 (35%) had progressive disease. Median PFS and OS were 7.4 and 12.7 months, respectively. Age was the only significant prognostic factor and tumor location (lobar versus multifocal versus corpus callosum) showed a trend. Grade 3-4 toxicities included thrombocytopenia (n=11) and neutropenia (n=7) for both pre- and post-RT chemotherapy. Four patients required platelet transfusions. No patient discontinued treatment because of toxicity. CONCLUSIONS: The combination of BCNU plus temozolomide as neo-adjuvant therapy in inoperable GBM exhibited promising activity with a good safety profile and warrants further evaluation.

Adult↗
PubMed2005

[Place of chemotherapy and radiotherapy in the management of oligodendrogliomas].

Twenty years ago, the discovery of the chemosensitivity of anaplastic oligodendrogliomas considerably boosted interest for these tumors. In spite of difficulties for histological diagnosis, numerous studies on radiotherapy and chemotherapy for oligodendrogliomas appeared these last years. They allowed to detail the appropriate role for these therapeutics. For low grade oligodendrogliomas, radiotherapy delays the anaplastic transformation, but does not modify the overall survival; its indication has to be discussed particularly in the absence of clinical symptoms. Chemotherapy seems to be effective for low grade oligodendrogliomas as well as anaplastic tumors. However, phase III studies are necessary to clarify the contribution of chemotherapy for the treatment of low grade oligodendrogliomas, mainly in relation to radiotherapy. In anaplastic oligodendrogliomas, in spite of the lack of phase III studies, radiotherapy seems to be effective. Chemotherapy is clearly effective, but the most appropriate timing (neoadjuvant, adjuvant, at recurrence) is unknown. Results of current prospective studies are awaited. Recently, molecular genetic analysis, particularly the loss of 1p and 19q chromosomes appears to demonstrate a genetic influence on both prognosis and response to treatment.

Brain Neoplasms↗
PubMed2005

[New place of the chemotherapy in gliomas].

During these last 25 years, despite numerous phases III studies, standard of treatment in glioblastoma multiforme (GBM) consisted of surgery and post-operative radiotherapy, while benefit of chemotherapy was a matter of debate. A phase III study, conducted by EORTC and NCI Canada and involving 573 patients, concluded clearly to the benefit of adding temozolomide during and after radiotherapy as adjuvant treatment. Using this schedule, median survival increase from 12,1 to 14,6 months, and 2 year survival rate from 8 to 26%. In the same time, for anaplastic oligodendroglioma (AO) the phase III study conducted by Cairncross, that compared radiotherapy to a schedule that deliver a chemotherapy with PCV followed by radiotherapy, failed to determine a significant benefit on overall survival, despite the particular chemosensitivity of theses tumors. Moreover, these two studies did underlined impact of biological markers (methylation of the promoter of O6 methylguanine DNA transferase (MGMT) gene for GBM and chromosomes 1p and 19q deletion for AO), that may become decisional markers in the future. We review here the new place of chemotherapy in the adjuvant treatment of GBM and anaplastic gliomas, as well as the impact of these pivotal studies on second lines therapies, and future clinical research.

Antineoplastic Agents, Alkylating↗
PubMed2004

Initial chemotherapy in gliomatosis cerebri.

BACKGROUND: Because of the diffuse nature of gliomatosis cerebri (GC), surgery is not suitable, and large field radiotherapy carries the risk of severe toxicity. In this setting, initial chemotherapy warrants further investigation. METHODS: The authors treated 63 consecutive patients with GC with initial chemotherapy consisting of either PCV (procarbazine, 60 mg/m2 on days 8 to 21; CCNU, 110 mg/m2 on day 1; and vincristine, 1.4 mg/m2 on days 8 and 29) or temozolomide (TMZ; 150 to 200 mg/m2 for 5 days every 4 weeks). There were 40 men and 23 women, with a median age of 48 years (range, 17 to 74 years) and a median Karnofsky performance status of 90 (range, 50 to 100). GC was initially present at diagnosis in 49 patients (primary GC), whereas 14 patients with a circumscribed glioma at onset developed secondary GC after a median follow-up period of 5.11 years. GC was classified based on the predominant tumor cells as astrocytic, oligodendroglial, or mixed GC. RESULTS: Seventeen patients received 1 to 6 cycles (median, 5) of PCV, and 46 received 2 to 24 courses (median, 13) of TMZ. Grade 3 to 4 hematologic toxicity was seen in 4 of 17 (23.5%) patients treated with PCV and in 4 of 46 (8.6%) of those treated with TMZ. Clinical objective responses were observed in 21 of 63 (33%) patients, and radiologic responses were seen in 16 of 62 (26%), with no significant difference between the two regimens. For all patients combined, the median progression-free survival (PFS) and overall survival (OS) were 16 months and 29 months, respectively. Regardless of the chemotherapeutic regimen, oligodendroglial GC had a better prognosis than astrocytic and oligoastrocytic GC in terms of PFS (p < 0.02) and OS (p < 0.0001). CONCLUSION: Initial chemotherapy is useful for some patients with gliomatosis cerebri. Temozolomide is well tolerated and appears to be a valuable alternative to procarbazine-CCNU-vincristine, especially for those with slow-growing, low-grade GC.

Adolescent↗
PubMed2004

[Hydroxyurea treatment for unresectable meningioma].

BACKGROUND: Management of unresectable progressive meningioma remains controversial and constitutes a major challenge since therapeutic options including chemotherapy and hormone modulation are limited. Recent data have suggested that hydroxyurea treatment may have an antitumoral effect. The purpose of this prospective phase II study was to evaluate the efficacy of hydroxyurea treatment for unresectable progressive meningioma. METHODS: From 1997 to 1999, consecutive patients presenting unresectable meningioma with clinically and/or neuroradiologically documented progression were considered for entry into this protocol. Previous radiotherapy was not a mandatory inclusion criteria. Treatment consisted of continuous oral administration of hydroxyurea at a dose of 20 mg/kg per day. Follow-up assessment included physical examination, computed tomography (CT), and magnetic resonance imaging (MRI) performed every three months, as well as regular blood testing. The primary endpoint was documentation of objective response by MRI or CT. RESULTS: The intent-to-treat population was 43 patients with at least 18 months follow-up. Median age was 60.4 years. Twenty-eight patients had undergone surgery following initial diagnosis. The meningioma was located in the skull base in 67% of patients. Histology was benign in 18 and atypical in 10. The eligible population included 36 patients with documented progressive disease at the time of inclusion; with progression documented clinically in 29 (67.5%) and/or radiologically in 20 (46%). In 7 patients, clinical or radiological progression could not be confirmed. The intent-to-treat analysis at median 26 months follow-up revealed objective response to hydroxyurea in only 3 patients (7%) including one on the basis of improvement in visual symptoms and two on MRI analysis. Progressive disease was observed clinically or radiologically in 26 patients (60.5%). Of the eligible population (n=36), 2 achieved an objective response and 13 (36%) exhibited stabilization under hydroxyurea therapy, while 21 (58%) progressed under treatment. Overall tolerance was good but anemia (grade I-II) and asthenia (grade I-II) were observed in 28% and 23.5% respectively. Treatment was discontinued in 3 patients because of chronic skin toxicity in one and anemia and asthenia in two. CONCLUSION: Hydroxyurea treatment is of marginal efficacy for meningioma and must not be considered as an alternative if radiotherapy or surgery is feasible. New efficient medical treatments are still required for progressive meningiomas.

Adult↗
PubMed2003

Chemotherapy alone as initial treatment for primary CNS lymphoma in patients older than 60 years: a multicenter phase II study (26952) of the European Organization for Research and Treatment of Cancer Brain Tumor Group.

PURPOSE: To assess the efficacy and toxicity of chemotherapy alone in patients older than 60 years with primary CNS lymphoma. PATIENTS AND METHODS: Fifty patients with a median age of 72 years and a median Karnofsky performance score (KPS) of 50 were eligible for this multicenter phase II study. The protocol consisted of high-dose methotrexate (MTX), lomustine, procarbazine, methylprednisolone, and intrathecal chemotherapy with MTX and cytarabine. The patients received one induction cycle; if objective response was achieved, five additional maintenance cycles were administered every 6 weeks. The median follow-up of patients was 3 years. RESULTS: Twenty four patients (48%) achieved an objective response (compete response [CR], 42%; partial response, 6%), with a median duration of CR of 27 months (range, 3 to 47+ months). Overall median survival time was 14.3 months, and 1-year progression-free survival was 40% (95% confidence interval [CI], 26% to 53%). Myelosuppression was the most frequent side effect, with grade 3 to 4 neutropenia in 19% of patients. One patient died during chemotherapy, as a result of pulmonary embolism. Most patients improved or preserved their cognitive functions (47% and 45% of the patients, respectively) and KPS (36% and 52% of the patients, respectively) until relapse, whereas cognitive and KPS decline attributed to delayed treatment neurotoxicity occurred in 8% and 12% patients, respectively. CONCLUSION: In the elderly, this chemotherapy regimen compares favorably with radiotherapy (RT) alone and reduces considerably the risk of delayed neurotoxicity associated with combined chemoradiotherapy. Chemotherapy alone is an appropriate strategy in older patients to delay or avoid RT.

Age Factors↗
PubMed2003

Phase II study of first-line chemotherapy with temozolomide in recurrent oligodendroglial tumors: the European Organization for Research and Treatment of Cancer Brain Tumor Group Study 26971.

PURPOSE: Oligodendroglial tumors are chemotherapy-sensitive tumors, with two thirds of patients responding to combination chemotherapy with procarbazine, lomustine, and vincristine (PCV). Temozolomide (TMZ), a new alkylating and methylating agent, has demonstrated high response rates in patients with recurrent anaplastic astrocytoma. We investigated TMZ as first-line chemotherapy in recurrent oligodendroglial tumors (OD) and mixed oligoastrocytomas (OA) after surgery and radiation therapy. PATIENTS AND METHODS: In a prospective, nonrandomized, multicenter, phase II trial, patients were treated with 200 mg/m2 of TMZ on days 1 through 5 in 28-day cycles for 12 cycles. Patients with a recurrence after prior surgery and radiotherapy, and with measurable and enhancing disease on magnetic resonance imaging (MRI) were eligible for this study. Patients with large lesions and mass effect or with new clinical deficits were not eligible. Pathology and the MRI scans of all responding patients were centrally reviewed. RESULTS: Thirty-eight eligible patients were included. In three patients, pathology review did not confirm the presence of an OD or OA. TMZ was generally well tolerated. The most frequent side effects were hematologic; only one patient discontinued treatment for toxicity. In 20 (52.6%) of 38 patients (95% exact confidence interval, 35.8% to 69.0%), a complete (n = 10) or partial response to TMZ was observed. The median time to progression was 10.4 months for all patients and 13.2 months for responding patients. At 12 months from the start of treatment, 40% of patients were still free from progression. CONCLUSION: TMZ provides an excellent response rate with good tolerability in chemotherapy-naive patients with recurrent OD. A randomized phase III study comparing PCV with TMZ is warranted.

Adult↗
PubMed2003

Clinical implications of quantitative real-time RT-PCR analysis of hTERT gene expression in human gliomas.

The presence of telomerase activity in a glioma may be a predictor of its malignant potential. Activation of telomerase is regulated at the transcriptional level of the human telomerase reverse transcriptase (hTERT). Here, we evaluated whether the amount of hTERT mRNA provides a molecular marker of glioma malignancy that would have clinical utility. We used a real-time RT-PCR to assess the number of hTERT transcripts in primary tumour samples derived from 70 glioma patients. Results were standardised by quantifying the number of ABL transcripts as internal control and expressed as hTERT/ABL ratio. The percentage of patients with detectable hTERT mRNA markedly increased with enhanced malignancy: low-grade gliomas expressed hTERT in one out of 14 cases (7.1%), anaplastic gliomas in four out of 13 cases (30.8%) and glioblastoma multiforme (GBM) tumours in 30 out of 43 cases (69.8%). The mean hTERT/ABL ratio was significantly higher in GBMs than in non-GBMs. Subdividing hTERT/ABL ratios as low (< pr = 25%) and high (>25%), we found that the overall survival among hTERT-positive GBMs was significantly worse in high hTERT expressors than in low hTERT expressors (P=0.0082). We conclude that the amount of hTERT mRNA may represent a diagnostic and prognostic indicator for GBM patients.

Adult↗
PubMed2003

Second-line chemotherapy with temozolomide in recurrent oligodendroglioma after PCV (procarbazine, lomustine and vincristine) chemotherapy: EORTC Brain Tumor Group phase II study 26972.

BACKGROUND: Oligodendroglial tumors are chemosensitive, with two-thirds of patients responding to PCV combination chemotherapy with procarbazine, lomustine (CCNU) and vincristine. Temozolomide (TMZ), a new alkylating and methylating agent has shown high response rates in recurrent anaplastic astrocytoma. We investigated this drug in recurrent oligodendroglial tumors (OD) and mixed oligoastrocytomas (OA) after prior PCV chemotherapy and radiation therapy. PATIENTS AND METHODS: In a prospective non-randomized multicenter phase II trial patients were treated with TMZ 150 mg/m(2) on days 1-5 in cycles of 28 days for 12 cycles. Eligible patients had a recurrence after prior PCV chemotherapy, with measurable and enhancing disease as shown by magnetic resonance imaging. Pathology and all responses were centrally reviewed. RESULTS: Thirty-two eligible patients were included. In four patients the pathology review did not confirm the presence of an OD or OA. Twelve of 24 patients [50%, 95% confidence interval (CI) 29% to 71%] evaluable for response to first-line PCV chemotherapy had responded to PCV. Temozolomide was in general well tolerated; the most frequent side-effects were hematological. One patient discontinued treatment due to toxicity. In seven of 28 patients (25%, 95% CI 11% to 45%) with histologically confirmed OD an objective response to TMZ was observed. Median time to progression for responding patients was 8.0 months. After 6 and 12 months from the start of treatment, 29% and 11% of patients, respectively, were still free from progression. CONCLUSIONS: TMZ may be regarded as the preferred second-line treatment in OD after failure of PCV chemotherapy. Further studies on TMZ in OD are indicated.

Adult↗
PubMed2001

Chemotherapy for the treatment of oligodendroglial tumors.

Oligodendroglial tumors include the highly chemosensitive oligodendroglioma and mixed oligoastrocytoma. Patients with these tumors have a longer median survival and time to disease progression than patients with other brain tumor types, but the range is wide and the disease is inevitably fatal. Because of their chemosensitivity and the potential for radiation toxicity, low-grade oligodendroglioma are increasingly being treated with adjuvant or neoadjuvant chemotherapy before radiation therapy. Approximately two thirds of patients with the more aggressive form (anaplastic oligodendroglioma) have shown substantial response to first-line procarbazine/lomustine/vincristine (PCV) therapy. However, experience with chemotherapy for relapse of disease following PCV therapy is limited. Several small trials have shown the safety and activity of temozolomide (Temodar in the United States, Temodal globally; Schering Corporation, Kenilworth, NJ) in oligodendroglioma, regardless of prior PCV therapy. An open-label, phase II trial of temozolomide in 47 patients with relapsed oligodendroglioma showed an objective response rate of 43%, of which seven (15%) were complete responses. Median progression-free survival was 6 months and 34% of patients were disease-free at 12 months. Median survival was 26 months for complete responders and 11 months for partial responders. Temozolomide was well tolerated. The only grade (3/4) toxicity with temozolomide treatment was thrombocytopenia, which occurred in < or = 5% of the 382 treatment cycles administered. The encouraging results of ongoing trials with temozolomide suggest the potential for its use as a first-line therapy in this patient population.

Antineoplastic Agents, Alkylating↗
PubMed2001

Long-term tumor control and functional outcome in patients with cavernous sinus meningiomas treated by radiotherapy with or without previous surgery: is there an alternative to aggressive tumor removal?

OBJECTIVE: We report the long-term follow-up of 31 patients with cavernous sinus meningiomas who were treated either with surgery and radiotherapy (RT) or with RT alone. This retrospective review was undertaken to compare long-term efficacy and morbidity of RT with or without previous surgery versus complete, aggressive surgical removal. METHODS: Between 1980 and 1997, we performed a retrospective study of 31 patients harboring cavernous sinus meningiomas. The patient group comprised 25 women and 6 men. Patients were divided into two therapeutic categories: patients treated with surgery and RT (Group I, 17 patients) and patients treated with RT alone (Group II, 14 patients). Twenty-five patients (14 in Group I and 11 in Group II) were treated for primary tumors, and 6 patients (3 in Group I and 3 in Group II) were treated for recurrent disease. All three patients who were treated by RT alone at the time of recurrent disease had had previous surgery as initial treatment. Tumor control, treatment morbidity, and functional outcomes were evaluated for all patients. Twenty-eight patients were alive at the time of analysis, with a median follow-up period of 6.1 years. RESULTS: The progression-free survival rate was 92.8% at 10-year follow-up. Only two patients exhibited tumor progression after initial treatment. One of the patients who experienced tumor regrowth 4 years after surgery and RT benefited from additional conventional external beam radiation, and this patient exhibited no evidence of tumor progression at the last follow-up examination 6 years later. Two patients experienced cranial nerve impairment after surgery, and no patients developed late radiation toxicity. Follow-up status as measured by the Karnofsky Performance Scale deteriorated in 7% of patients and was the same or improved in 93% of patients. CONCLUSION: The results of combined surgery and RT or RT alone indicated a high rate of tumor control and a low risk of complications. Complete aggressive surgical removal of cavernous sinus meningiomas is associated with an increased incidence of morbidity and mortality and does not demonstrate a better rate of tumor control. Conventional external beam radiation seems to be an efficient and safe initial or adjuvant treatment of these lesions, and these findings should serve as a basis for evaluating new alternatives such as radiosurgery or stereotactic RT.

Adult↗
PubMed2001

[Burkitt lymphoma of the cavernous sinus. Apropos of a case].

Cavernous sinus lymphoma is a rare occurrence. We report a case of a 37-year-old woman who was admitted for an oculo-motor paresis and retro-orbital pain. CT scan and MRI disclosed a cavernous sinus tumor. A surgical biopsy was performed through a pterional approach and the histological diagnosis was a solitary primary Burkitt's lymphoma. Aggressive chemotherapy led to a complete and asymptomatic remission after a follow-up of 9 years. The mechanism of the primary localization in the cavernous sinus is discussed.

Adult↗
PubMed1998

Prognostic significance of Ki67, p53 and epidermal growth factor receptor immunostaining in human glioblastomas.

Since glioblastomas in adults are uniformly fatal, evaluation of easily reproducible prognostic criteria which would attempt to define groups of patients is required. However, there is lack of a clear consensus regarding the expression of some markers in the literature. Therefore, an immunohistochemical study was performed to determine the prognostic significance of Ki67, p53, and epidermal growth factor receptor (EGFR) in a retrospective series of 63 glioblastomas. Image analysis was carried out in positive specimens to quantify the immunoprecipitates. p53 and EGFR expression were specifically addressed in the 36 primary glioblastomas reported in this series. In all cases, clinical data (age, Karnofsky performance scale index [KPS] before surgery, extent of surgery) and immunohistochemical features were analysed using univariate and multivariate analysis to ascertain whether any significant correlation exists between [1] EGFR expression [2], p53 accumulation [3], Ki67 labelling index and prognosis (survival time and disease-free survival time, DFST). The results showed that in this series of glioblastomas, none of these markers had any prognostic value. Among the clinical parameters, a high KPS before surgery was found to be indicative of a shorter DFST and survival time (P < 0.05), whereas a younger age at onset and total or subtotal surgical excision were associated with a longer survival (P < 0.001 and 0.05, respectively). EGFR protein accumulation was inversely correlated with p53 accumulation (P = 0.01). The percentage of the primary glioblastomas expressing EGFR was much lower in our study (33%) than in the literature suggesting that the molecular distinction between primary and secondary glioblastomas is not so clear-cut.

Aged↗
PubMed1996

Divergent effect of TGFbeta1 on growth and proteolytic modulation of human prostatic-cancer cell lines.

Plasminogen activators (PAs) play a key role in malignant transformation. PA secretion by tumoral cells is strongly correlated with their aggressive phenotype. Regulation of invasive potential by growth factors has been also demonstrated. This study was designed to investigate the effects of 5alpha-dihydrotestosterone (DHT), epidermal growth factor (EGF), transforming growth factor beta1 (TGFbeta1), retinoic acid and basic fibroblastic growth factor (bFGF) on cell growth and PA expression and secretion in DU145 and PC3 cells, 2 human prostatic-cancer cell lines. The proliferation of 2 cell lines was significantly increased only by EGF (about 30%), but decreased by TGFbeta1 (40% inhibition). However, EGF-treated cells showed significant enhancement (about 400%) of u-PA secretion. A similar effect was observed when cells were cultured with DHT (200%) and with TGFbeta1 (300%). Nevertheless, u-PA mRNA level in EGF-, TGFbeta1 - or DHT-treated cells was amplified only between 110 and 180% of control, suggesting that growth factors differently controlled the steps of PA expression. Furthermore, our results clearly showed the divergent effect of TGFbeta1, i.e., an inhibition of prostatic-cell-line growth accompanied by an increase in proteolytic activity.

Bone Marrow↗
PubMed1996

Pineal region tumors: the role of stereotactic radiosurgery.

Between July 1992 and August 1995, 11 patients with pineal region tumors (PRTs) were treated at our center. Ages ranged from 8 to 72 years (median 21). Diagnosis was confirmed by histological examination in 7 patients. The remaining cases had strong neuroradiological and marker evidence of the diagnosis, so that a stereotactic biopsy could be avoided. The pathological diagnoses were pinealocytoma (n = 1), tectal astrocytoma (n = 1), germinoma (n = 2), pinealoblastoma (n = 2), and meningioma (n = 3). The marginal dose of these tumors ranged from 12 to 18-20 Gy. Conventional external radiotherapy was never used in this series. With a median follow-up of 12.3 months (range 2-34), all tumors responded to treatment and disappeared or ceased growing. We observed no mortality or major morbidity. One patient (tectal astrocytoma) had a mild radiation-induced reaction, with headache and transient worsening of an abducent nerve palsy, which were controlled with steroids. In germinomas and pinealoblastomas, recovery of normal cerebrospinal fluid circulation was observed in less than 7 days, in parallel with major tumor shrinkage. In this study we confirm that radiosurgery can be an effective and safe alternative for the treatment of pinealocytomas and low-grade tectal gliomas. Moreover, we consider that the characteristics of the radiosurgery technique suggest the method should be evaluated for the treatment of malignant PRTs.

Adolescent↗