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M Gardiman

Publications and source records attributed to M Gardiman.

At least 19 recordsLinked to original sources
PubMed2006

Is protracted low-dose temozolomide feasible in glioma patients?

The authors investigated the safety of 75 mg/m2 temozolomide for 21 days every 28 days in glioma patients. This schedule could lead to DNA repair enzyme O6-alkylguanine-DNA alkyltransferase depletion, contributing to overcoming drug resistance. Although Phase III studies are forthcoming, no data are available on the long-term toxicity of temozolomide, which, in this series, incurred prolonged, cumulative lymphopenia, which leads to a high incidence of infections.

Adult↗
PubMed2006

Clinical and pathological characteristics of patients presenting with biochemical progression after radical retropubic prostatectomy for pathologically organ-confined prostate cancer.

INTRODUCTION: To identify risk factors for biochemical failure after radical prostatectomy (RP) in men with pathologically organ-confined (OC) prostate cancer (PCa). MATERIALS AND METHODS: Clinical and pathological features of 350 consecutive patients with pathologically OC PCa treated only with RP and bilateral pelvic lymphadenectomy were analyzed, retrospectively, to identify predictor parameters of prostate-specific antigen (PSA) failure (PSA>or=0.4 ng/ml). The median follow-up was 58.6 months (range: 3.9-183 months). All pathological specimens were step sectioned at 4-mm intervals. Kaplan-Meier progression-free survival rates and chi2 test were adopted for statistical analyses. Multivariate Cox proportional hazard regression models were used to test the association between pathological Gleason score and surgical margin status. RESULTS: 67 patients (19.1%) failed at a median follow-up of 40.2 months (range 1.9-123.3). Age and preoperative PSA failed to reveal significance also in patients with serum PSA>or=20 ng/ml (p=0.46). Patients with T3 clinical stage had a higher progression rate compared to T1C and T2 (43.5 vs. 27.8 and 17.3%, respectively) even if no high statistical significance was pointed out. Presence of perineural infiltration (p=0.04) and prostatic apex infiltration (p=0.74) in the prostatectomy specimens failed to reveal significance. A high pathological Gleason score (>or=7; p=0.0003) and surgical margin status (p<0.0001) were shown to be the most powerful predictive parameters of biochemical progression. CONCLUSIONS: In patients with pathologically OC PCa the presence of a high pathological Gleason score and positive surgical margins appear to represent the most important factors for prediction of outcome following RP.

Aged↗
PubMed2002

Photofrin as a specific radiosensitizing agent for tumors: studies in comparison to other porphyrins, in an experimental in vivo model.

The use of ionizing radiation for tumor treatment represents a well established therapeutic modality. The efficiency and selectivity of radiotherapeutic protocols can be often enhanced by the addition of specific chemical compounds that optimise the response of the tumor to the incident radiation as compared with peritumoral tissue districts. The results of this study showed that Photofrin, a porphyrin derivative which is presently used as a tumor-photosensitizing agent in photodynamic therapy (PDT), can also act as an efficient tumor radiosensitizer. To test this possibility, we used nude mice subcutaneously implanted with human bladder cancer RT4. The mice were injected with different porphyrin-type photosensitizing agents, including Photofrin, 5-aminolevulinic acid, chlorin e(6), haematoporphyrin, protoporphyrin, Zn-tetrasulphophtalocyanine, and irradiated with 5 and 15 Gy using a Siemens X-ray device. Even though all the porphyrins accumulated in significant amounts in the neoplastic lesion, only Photofrin significantly improved the response of the tumor to irradiation by increasing the doubling time of the tumor volume from 6.2 days in the untreated control group to 10.9 days in the 5 and 15 Gy-irradiated groups. The tumor response was maximal with injected Photofrin doses of 7.5 mg/kg, and was not further enhanced by injection of higher doses. Our hypothesis is, that the radiosensitizing effect of Photofrin seems to be due to some oligomeric constituents which could specifically react with radiogenerated-radicals thereby amplifying the effect of the X-ray radiation.

Animals↗
PubMed2001

Temozolomide as a second-line systemic regimen in recurrent high-grade glioma: a phase II study.

BACKGROUND: To investigate the efficacy of temozolomide in relation to response rate, toxicity, time to progression. and median survival time, a phase II study was conducted in patients with recurrent high-grade glioma following surgery plus radiotherapy and first-line chemotherapy based on nitrosourea, procarbazine and vincristine. PATIENTS AND METHODS: Forty-one patients with high-grade glioma, at second recurrence or progression, of which twenty-two (54%) had glioblastoma multiforme, ten (24%) anaplastic astrocytoma, and nine (22%) anaplastic oligodendroglioma were administered temozolomide, 150 mg/m2/daily for five days every four weeks. RESULTS: Response was assessed in 40 patients. The overall response rate (complete + partial response) was 22.5% (95% confidence interval (CI): 9.5%-35%). The median time to progression for all 41 patients was 22.3 weeks; progression-free survival at 6 and 12 months was 48.5% and 34.7%, respectively. Median survival time was 37.1 weeks with 80.2% at 6 and 34.9% survival at 12 months. CONCLUSIONS: On multivariate analysis, response to previous treatment was significant (P = 0.03) for time to progression and Karnofsky performance score for overall survivall (P = 0.002). Temozolomide gave a moderate response rate with acceptable toxicity as second-line chemotherapy in patients with recurrent high-grade glioma.

Adult↗
PubMed2001

Clear-cell meningioma in a 22-month-old male: a case report and literature review.

We report a case of spinal clear-cell meningioma occurring in a 22-month-old male who presented a right limp and then refused to walk. Spinal magnetic resonance imaging demonstrated a large, intradural tumor from T(11) to L(4), which was totally excised. The patient's postoperative recovery was uneventful and 5 months after surgery he began walking again. The latest follow-up magnetic resonance imaging of the brain and spine, obtained 42 months after diagnosis, was negative for tumor recurrence. Though clear-cell meningioma is a rare form of meningioma, it should be considered in the differential diagnosis of any space-occupying lesion of the spine arising in very young children. Complete surgical removal is necessary because it is potentially aggressive and may recur. After surgery, an accurate follow-up is warranted.

Humans↗
PubMed2000

Chemotherapy in patients with recurrent and progressive central neurocytoma.

BACKGROUND: Recurrent central neurocytoma is very rare and to the authors' knowledge data regarding its response to chemotherapy currently are not available. METHODS: Three patients with progressive neurocytoma received chemotherapy after their informed consent was obtained. Disease recurred in two patients after surgery and radiotherapy and in one patient after surgery. The treatment regimen was comprised of etoposide, 40 mg/m(2)/day, for 4 days; cisplatin, 25 mg/m(2)/day, for 4 days; and cyclophosphamide, 1,000 mg/m(2), on Day 4; this cycle was repeated every 4 weeks. RESULTS: Stabilization of disease was observed in 2 patients and complete remission was observed in 1 patient; at last follow-up, these responses had been maintained for 15 months, 18 months, and 36 months, respectively. CONCLUSIONS: In this small series, this therapeutic regimen led to long term disease reduction, and merits further study.

Adult↗
PubMed2000

Loss of FHIT expression in transitional cell carcinoma of the urinary bladder.

Cytogenetic and loss of heterozygosity (LOH) studies demonstrated chromosome 3p deletions in transitional cell carcinoma (TCC). We recently cloned the tumor suppressor gene FHIT (fragile histidine triad) at 3p14.2, one of the most frequently deleted chromosomal regions in TCC of the bladder, and showed that it is the target of environmental carcinogens. Abnormalities at the FHIT locus have been found in tumors of the lung, breast, cervix, head and neck, stomach, pancreas, and clear cell carcinoma of the kidney. We examined six TCC derived cell lines (SW780, T24, Hs228T, CRL7930, CRL7833, and HTB9) and 30 primary TCC of the bladder for the integrity of the FHIT transcript, using reverse transcriptase-polymerase chain reaction (RT-PCR) to investigate a potential role of the FHIT gene in TCC of the bladder. In addition, we tested expression of the Fhit protein in the six TCC-derived cell lines by Western blot analysis and in 85 specimens of primary TCCs by immunohistochemistry. Three of the six cell lines (50%) did not show the wild-type FHIT transcript, and Fhit protein was not detected in four of the six cell lines (67%) tested. Fhit expression also was correlated with pathological and clinical status. A significant correlation was observed between reduced Fhit expression and advanced stage of the tumors. Overall, 26 of 30 (87%) primary TCCs showed abnormal transcripts. Fhit protein was absent or greatly reduced in 61% of the TCCs analyzed by immunohistochemistry. These results suggested that loss of Fhit expression may be as important in the development of bladder cancer as it is for other neoplasms caused by environmental carcinogens.

Acid Anhydride Hydrolases↗
PubMed1998

Unusual nasal and orbital involvement of glioblastoma multiforme: a case report and review of the literature.

We describe a case of glioblastoma treated with chemoradiotherapy that spread to the dura mater with direct invasion of the skull base, protrusion into the homolateral nasal fossa, and penetrated of the frontal sinus, the orbital wall and the ethmoidal sinuses. Only eight cases of glioblastoma showing this development have been described in the literature; one of these, however, had a sarcomatous component which was absent in our case.

Aged↗
PubMed1997

Diencephalic syndrome and disseminated juvenile pilocytic astrocytomas of the hypothalamic-optic chiasm region.

BACKGROUND: Diencephalic syndrome (DS) is a complex of signs and symptoms related to hypothalamic dysfunction; its main features are emaciation, despite a normal or slightly diminished caloric intake, and an alert appearance. DS has been almost exclusively described in association with space-occupying lesions of the hypothalamic-optic chiasm region, mainly juvenile pilocytic astrocytoma (JPA). A systematic diagnostic approach, including contrast-enhanced magnetic resonance imaging (MRI) of the child's head, is rapidly expanding our knowledge of this syndrome. METHODS: The MRI findings for three children affected by DS associated with biopsy-proven JPA, consecutively referred to the Pediatric Neuro-Oncology Program of the Department of Pediatrics at the University of Padua between September 1991 and January 1996, are presented in this article. The children were boys, ages 6, 7, and 18 months, respectively. RESULTS: In all three patients, the initial contrast-enhancing MRIs of the head showed evidence of tumor dissemination. This finding prompted a study of the spine, which in turn showed tumor deposits in all three subjects. Among the 43 patients younger than 16 years with low grade astroctyoma who consecutively entered the Neuro-Oncology Program during the study period, these 3 patients were the only ones who had disseminated tumors. CONCLUSIONS: In this study, the hypothesis was formulated that DS and disseminated hypothalamic-optic chiasm JPA tend to be more commonly associated than previously stated. This study suggests that the initial contrast-enhanced MRI of the head of a child affected by DS and hypothalamic JPA must be looked at carefully for evidence of tumor dissemination, and that the spine must also be examined if the findings are positive.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Gene expression and autoradiographic localization of endothelin-1 and its receptors A and B in the different zones of the normal human prostate.

PURPOSE: To investigate the gene expression and tissue distribution of prepro Endothelin-1 (ET-1), Endothelin Converting Enzyme (hECE-1), and ETA and ETB receptors in the central (CZ), transition (TZ) and peripheral (PZ) zones of normal human prostates. MATERIALS AND METHODS: Sections of the different zones of histologically normal prostates from 35 year-old men were obtained and autoradiographically studied with 125I ET-1 with and without the ETA antagonist BQ-123, the ETB agonists sarafotoxin 6C, and excess cold ET-1. Specimens from PZ and CZ and DU145 and PC3 human prostate cancer cell lines were also investigated by reverse transcription (RT)-PCR. RESULTS: The mRNAs of all genes were detected in all specimens examined. No ETB expression was found in either cell lines. Specific intense 125I ET-1 binding with clear-cut differences among zones was found. In the CZ the main subtype in the glandular stroma and epithelium was the ETA and ETB, respectively, in the PZ the opposite was true. In PZ, the ETA receptors were detected on the glandular epithelium; in the TZ both receptor subtypes were only in the stroma. CONCLUSIONS: These receptors' zonal distribution differences may be relevant for the pathogenesis of BPH and prostatic cancer.

Adult↗
PubMed1996

Cytoskeletal and cytocontractile protein composition of stromal tissue in normal, hyperplastic, and neoplastic human prostate. An immunocytochemical study with monoclonal antibodies.

Monoclonal antibodies specific for protein markers of smooth muscle and nonmuscle cell differentiation were applied to cryosections of normal, hyperplastic, and neoplastic human prostate specimens in order to determine whether differences in the distribution of target antigens could be detected among the various tissues. Immunofluorescence assays showed that vimentin, desmin, smooth-muscle-type alpha-actin, and both smooth muscle and nonmuscle myosin heavy chains do not change their patterns of labeling in the stromas of normal, BPH, and carcinomatous prostates. By contrast, cytokeratin 18, a differentiation marker of simple epithelia, and to a lesser extent cytokeratin 8, was consistently found in stromal tissue of the "transition zone", but only scarcely in the stroma of the "peripheral zone" from normal prostate, and was completely unexpressed in benign hyperplasia. Prostatic carcinoma from the "peripheral zone" expressed this cytoskeletal component only in trace amounts. Moreover, in prostate showing coexistence of hyperplasia and neoplasia (in the "peripheral zone"), the stroma of BPH closely resembled the stroma surrounding the carcinoma; that is, it was completely unreactive with the anti-cytokeratin 18 antibody. Expression of cytokeratins in extraepithelial tissues has been previously correlated with the achievement of a proliferative state, notably in embryogenesis, in tissue regeneration, and in various pathological forms of proliferation and growth, including some tumors of mesenchymal origin. Our results indicate the following: (1) cells in the stromal tissue of normal prostate are of smooth muscle type and are heterogeneous as concerns cytokeratin distribution; (2) we show, for the first time, the existence of a marker that is differentially distributed in the "transition" versus "peripheral" zone; (3) the expression of cytokeratins in the stroma is lost with the development of hyperplasia and only partially recovers with neoplasia; (4) the pattern of stromal tissue, concerning cytokeratin 18 expression, does not change with different BPH locations ("transition" versus "peripheral" zone); and (5) contrary to expectations, cytokeratin 18 expression disappears in conditions presumably involving stromal cell proliferation.

Adult↗
PubMed1996

Early chemotherapy and concurrent radio-chemotherapy in high grade glioma.

PURPOSE: The poor results from treatment of high grade glioma prompted us to explore new protocols involving concurrent radio-chemotherapy. Our primary objective was to evaluate the feasibility of very early postoperative chemotherapy with BCNU, concurrent radio-chemotherapy with carboplatin and teniposide, and post-radiotherapy BCNU. Our secondary objectives were to evaluate time to progression, and overall survival. PATIENTS AND METHODS: We treated 24 newly diagnosed patients (pts) with BCNU 150 mg/m2 seven days after surgery. Thirty days later, we started radiotherapy, 1.8 to 2 Gy/day for 5 days a week on limited fields up to 60 Gy, and concurrent chemotherapy with carboplatin 250 mg/m2 on days 1, 22, and 43, and teniposide 50 mg/m2 on days 1, 2, 3, 22, 23, 24, 43, 44 and 45. Two cycles of 150 mg/m2 BCNU were then given at 30 and 70 days, respectively, after the end of the radio-chemotherapy course. Therapy was then suspended, but if disease progression was evident, treatment was resumed with drugs that had not been previously employed. Surgical reintervention was not routinely considered. RESULTS: Following radio-chemotherapy treatment in the 24 pts evaluable for response, we observed partial remissions in 8 cases (33%) and stable disease in 12 (50%). Actuarial estimates of progression free survival (PFS) were 33 weeks, with 56 wks for anaplastic astrocytoma and 31 weeks for glioblastoma. Median survival time (MST) of all pts was 58 weeks; 51 weeks for glioblastoma and was not reached for anaplastic astrocytoma. This regimen was feasible. Of 144 planned cycles, 139 were delivered, and among these only in 13 and 9 cycles the doses were reduced by 75 and 50%, respectively. We did not observe any gastrointestinal toxicity. Grade 2 hematological toxicity occurred in 25% of pts. grade 3 in 4% and neurological toxicity in 3% of the pts during BCNU delivery, probably due to a sharp increase in intracranial pressure. CONCLUSION: Early chemotherapy, concurrent chemo-radiotherapy and brief post-radio-therapy chemotherapy are feasible and well tolerated. The objective response and disease stabilization rates appear similar to previous experiences.

Adult↗
PubMed1995

[Solitary fibrous tumor of the pericardium].

A 60-year-old man with a large pericardial effusion was found to have a large intrapericardial mass located anteriorly to the right ventricle and firmly attached to the ascending aorta and pulmonary trunk. Histologically the mass, which was completely excised together with its large base of implant, was found to be a Solitary Fibrous Tumor. After a 46-months follow-up the patient is free from symptoms and signs of recurrence. Solitary Fibrous Tumor is considered a benign tumor and its excision curative, however aggressive variants and metastasis have been reported. Patternless architecture, fibrous collagenous stroma, exclusive vimentin positivity and the lack of ultrastructural mesothelial markers are important tools for the diagnosis. Because of the extreme rarity of intrapericardial location and lack of information on long-term behaviour of this tumor, close non-invasive follow-up is necessary.

Heart Neoplasms↗
PubMedDate not supplied

Meningeal melanocytoma: a rare lesion of the central nervous system.

Two cases of meningeal melanocytoma, both localized in the cerebellopontine angle, were studied. The patients underwent surgical excision, and in one case there was a recurrence. All the pathologic criteria of melanocytoma were fulfilled by the 2 reported cases. Immunohistochemical stainings were very important ancillary tools in the differential diagnosis with other pigmented meningeal tumors.

Adult↗
PubMedDate not supplied

Primary central nervous system lymphomas: clinico-pathologic and immunohistochemical analysis of 30 cases.

AIMS AND BACKGROUND: Primary Central Nervous System lymphomas are attracting mounting interest because of their increasing incidence in an immunocompetent population and as sporadic tumors. A new lymphoma classification has been proposed, based on new morphologic entities and on advanced immunologic and molecular techniques. METHODS AND RESULTS: The study concerns the clinical and pathologic characterization of 30 cases of primary central nervous system non-Hodgkin's lymphomas in non-HIV patients using a wide monoclonal antibodies panel. Comparative evaluation of effectiveness and reliability between surgery and stereotactic biopsies was made according to Kiel and Real lymphoma classifications. There were 24 high-grade and only 3 low-grade lymphomas. Three stereotactic biopsies were not diagnostic. CONCLUSIONS: Stereotactic procedures were confirmed as the most immediate and least aggressive approach to CNS tumors, but inadequate sampling caused a deadlock to a full lymphoma diagnosis, which requires immunohistochemical and sometimes also molecular studies. However, it should be stressed that morphologic criteria (tumor cell cytology and neoplastic cuffing of the vascular walls) maintain their diagnostic effectiveness.

Adult↗