Search NEL Online

Case Reports 2015; 36(1): 28-30 PubMed PMID: 25789596 Citation  Keywords:  Adult, Antineoplastic Agents:administration & dosage, Ergolines:administration & dosage, Follow-Up Studies, Humans, Male, Optic Chiasm:pathology, Pituitary Neoplasms:complications, Prolactinoma:complications, Treatment Outcome, Vision, Low:drug therapy,.   

: Giant prolactinoma is a rare subset of macroadenomas. Limited studies demonstrated which therapy could be successfully used in the first-line therapy of giant prolactinoma. We presented a case with a 54 × 40 × 40 mm pituitary adenoma and optic chiasmatic compression with left sphenoid sinus invasion. The tumor caused a loss of visual field of the right side. Cabergoline treatment was started with dose of 1.5 mg/week. Fifteen days later, the clinical visual acuity examination showed a significant improvement in the patient with visual field defect. After the five years follow-up magnetic resonance imagining showed reduction of the adenoma size (17 × 12 mm) was significant. Our findings suggest that, cabergoline can be used as a first-line therapy in giant prolactinomas because tumoral shrinkage without a surgical procedure and rapid improvement in visual field defect is achieved with this medical treatment....

Read abstract  Full text PDF

Case Reports 2012; 33(3): 260-264 PubMed PMID: 22635080 Citation  Keywords:  Adrenal Gland Neoplasms:diagnostic imaging, Adult, Antineoplastic Agents:administration & dosage, Drug Resistance, Neoplasm, Fatal Outcome, Female, Humans, Indoles:administration & dosage, Pheochromocytoma:diagnostic imaging, Pyrroles:administration & dos.   

: We report the clinical response and adverse events of a female patient treated for recurrent malignant pheochromocytoma using the tyrosine kinase inhibitor sunitinib. A 41-year-old woman underwent adrenectomy and nephrectomy forpotentially malignant adrenal pheochromocytoma. Fifty-four months after surgery, abdominal computed tomography (CT) and Iodine-131 metaiodobenzylguanidine((131)I-MIBG) scintigraphy revealed multiple tumors in the liver. Two chemotherapy protocols were administered in succession (first line: cyclophosphamide/vinblastine/dacarbazine; second line: cisplatin/docetaxel/ifomide). Despite these treatments, however, the tumors continued to progress. Treatment with sunitinib was initiated, but the patient quickly developed critical hypertension caused by tumor lysis syndrome. The sunitinib dose was reduced, and a partial response, as defined by the Response Evaluation Criteria in Solid Tumors (RECIST), was observed after 6 treatment cycles. Moreover, no severe adverse events occurred during this lower-dose sunitinib treatment. Unfortunately, sunitinib treatment became unaffordable for the patient, who eventually resorted to palliative care and died 37 months later. This case study is consistent with previous reports indicating that appropriate doses of sunitinib can induce a partial antitumor response in patients with refractory pheochromocytoma....

Read abstract  Full text PDF

Journal Article 2009; 30(Suppl 1): 60-66 PubMed PMID: 20027146 Citation  Keywords:  Antineoplastic Agents:administration & dosage, Autoradiography, Blotting, Western, Cell Line, Tumor, Cell Proliferation:drug effects, Cell Survival:drug effects, Chromatography, High Pressure Liquid, Cytochrome P-450 Enzyme System:metabolism, DNA Adducts:.   

OBJECTIVES: Ellipticine is a potent antineoplastic agent exhibiting multiple mechanisms of action with promising brain tumor specificity. This anticancer agent should be considered a pro-drug, whose pharmacological efficiency and/or genotoxic side effects are dependent on its cytochrome P450 (CYP) - and/or peroxidase-mediated activation to species forming covalent DNA adducts. Ellipticine can also act as an inhibitor or inducer of biotransformation enzymes, thereby modulating its own metabolism leading to its genotoxic and pharmacological effects. The toxicity of ellipticine to U87MG glioblastoma cells and mechanisms of its action to these cells are aims of this study.

METHODS: Ellipticine metabolites formed in U87MG cells were analyzed using HPLC. Covalent DNA modifications by ellipticine were detected by 32P-postlabeling. CYP enzyme expression was examined by QPCR and Western blot.

RESULTS: U87MG glioblastoma cell proliferation was efficiently inhibited by ellipticine. This effect might be associated with formation of two covalent ellipticine-derived DNA adducts, identical to those formed by 13-hydroxy- and 12-hydroxyellipticine, the ellipticine metabolites generated by CYP1A1, 1B1 and 3A4, lactoperoxidase and cyclooxygenase 1, the enzymes expressed in U87MG cells. Moreover, by inducing CYP1B1, 3A4 and 1A1 enzymes in U87MG cells, ellipticine increases its own enzymatic activation, thereby enhancing its own genotoxic and pharmacological potential in these cells. Ellipticine concentration used for U87MG cell treatment is extremely important for its pharmacological effects, as its metabolite profiles differed substantially predicting ellipticine to be either detoxified or activated.

CONCLUSION: The results found in this study are the first report showing cytotoxicity and DNA adduct formation by ellipticine in glioblastomas....

Read abstract  Full text PDF

Clinical Trial 2007; 28(6): 727-733 PubMed PMID: 18063933 Citation  Keywords:  Acromegaly:drug therapy, Adult, Antineoplastic Agents:administration & dosage, Blood Glucose:metabolism, Delayed-Action Preparations, Drug Administration Schedule, Female, Follow-Up Studies, Homeostasis:drug effects, Human Growth Hormone:blood, Humans, In.   

OBJECTIVE: To evaluate the short-term effects of Lanreotide Autogel on insulin sensitivity markers among acromegalic patients with pituitary tumors.

DESIGN: Prospective clinical trial with six months of follow-up.

SETTING: A tertiary endocrinology clinic.

MATERIALS AND METHODS: Naïve patients (patient No. 1 and patient No. 3) and patients who experienced prior somatostatin analogue treatment (patient No. 2, patient No. 4, and patient No. 5) were included. Before and after 6 months of Lanreotide Autogel therapy, insulin sensitivity in each subject was determined using homeostasis model assessment of insulin resistance and beta-cell function formula. Euglycemic hyperinsulinemic clamp test was also performed to evaluate whole insulin sensitivity and was indicated as an 'M' index.

RESULTS: All patients experienced reduction in their HOMA-beta. We noted major HOMA-beta decreases accompanied by pronounced increases in M indices for patients Nos. 1, 2 and 3 (1.03 vs. 8.22, 2.98 vs. 4.70, and 5.09 vs. 13.09, respectively). The increases in M indices of these patients were with marked decreases in GH levels (34.20 vs. 15.30 microg/l, 4.25 vs. 0.74 and 5.0 vs. 0.66 ng/mL, respectively). Minor decline in HOMA-beta and worsened M index and almost stable GH were observed in patients Nos. 4 and 5. Except for patient No. 3, all participants showed declining HOMA-IR.

CONCLUSIONS: Short-term Lanreotide Autogel treatment has been observed to improve M indices of acromegalic patients whose GH levels exhibited marked reduction. This amelioration seemed to be related to decreases in GH levels rather than to a direct drug effect....

Read abstract  Full text PDF

Clinical Trial 2003; 24(5): 334-338 PubMed PMID: 14647007 Citation  Keywords:  Adenoma:drug therapy, Adult, Antineoplastic Agents:administration & dosage, Apoptosis:drug effects, Female, Humans, Male, Middle Aged, Peptides, Cyclic:administration & dosage, Pituitary Neoplasms:drug therapy, Somatostatin:administration & dosage,.   

OBJECTIVES: Apoptosis of endocrine cells represents one of factors significantly affected the control of hormones secretion. Present study aimed to examine whether treatment of somatotropinoma types tumours with somatostatine analogue (lanreotide) results in apoptosis.

MATERIAL AND METHODS: The studies were performed on 35 patients with somatotropinoma type tumours on whom adenomectomy was performed by transsphenoidal approach. The operative material was examined by cellular morphology, based on light and electron microscopy and chromosomal ladder formation assay.

RESULTS: The number of apoptotic cells showed features typical for the process as condensation and fragmentation of chromatin, vacuolisation, damage of the inner structure of mitochondria and oligonucleosomal fragmentation of DNA was found in the study material. The results of the studies demonstrated the occurrence of lanreotide induced apoptosis in somatotropinoma type tumours. The grade of apoptotic cells in macroadenomas type adenomas, treated with lanreotide, ranged from 4.0% to 17.1% (mean 8.7+/-2.6%). Patients in whom hypophysectomy was not preceded by lanreotide treatment demonstrated low level of apoptotic cells (no more than 3.5%).

CONCLUSIONS: The studies showed that treatment with somatostatine analogue-lanreotide induced apoptosis of tumour cell suggesting that the induction of apoptotic cell death may be involved in the anticancer activity of somatostatine analogue....

Read abstract

Clinical Trial 2002; 23(4): 341-344 PubMed PMID: 12195238 Citation  Keywords:  Adjuvants, Immunologic:administration & dosage, Aged, Antineoplastic Agents:administration & dosage, Carcinoma, Neuroendocrine:drug therapy, Carcinoma, Renal Cell:drug therapy, Digestive System Neoplasms:drug therapy, Female, Humans, Injections, Subcutane.   

OBJECTIVES: The preliminary applications of the psychoneuroimmunological knowledges to the treatment of human diseases have confirmed the possibility to amplify IL-2-dependent anticancer immunity by the pineal hormone melatonin (MLT) or by opioid antagonist, such as naltrexone (NTX), which act by activating TH1 lymphocytes or suppressing TH2 lymphocytes, respectively. At present, however, there are no data about the immunobiological effects of a concomitant administration of both MLT and NTX on IL-2-induced anticancer immunity. This preliminary study was carried out to evaluate whether the association of NTX may further enhance the lymphocytosis induced by the neuroimmunotherapy with IL-2 plus MLT.

MATERIALS & METHODS: The study included 14 consecutive untreatable metastatic solid tumor patients. According to a cross-over randomized study, the patients were treated during two consecutive immunotherapeutic cycles at 21-day intervals with IL-2 plus MLT alone or with IL-2 plus MLT plus NTX. IL-2 was injected subcutaneously at 3 MIU/day for 6 days/week for 4 weeks, MLT was given orally at 20 mg /day in the evening every day, and NTX was given orally at 100 mg in the morning every next day. For the immune evaluation, venous blood samples were drawn before the onset of treatment and at weekly intervals.

RESULTS: Lymphocyte mean number significantly increased after both IL-2 plus MLT and IL-2 plus MLT plus NTX. However, the concomitant administration of NTX induced a significantly higher increase in lymphocyte mean number with respect to that achieved with IL-2 plus MLT alone. In contrast, the increase in eosinophil mean number was significantly higher on IL-2 plus MLT alone.

CONCLUSIONS: This preliminary study shows that the association of NTX further amplifies the lymphocytosis obtained by IL-2 plus MLT. Since the lymphocytosis represents the most important favourable prognostic variable predicting the anticancer efficacy of IL-2 immunotherapy, it is probable that a cancer neuroimmunotherapy with IL-2 plus both MLT and NTX to activate TH1 and suppress TH2 cells respectively, may deserve more promising results in the treatment of human neoplasms according to the psychoneuroimnunological knowledge....

Read abstract

Clinical Trial 2002; 23(3): 255-258 PubMed PMID: 12080288 Citation  Keywords:  Aged, Antineoplastic Agents:administration & dosage, Carcinoma, Renal Cell:drug therapy, Drug Therapy, Combination, Female, Humans, Injections, Subcutaneous, Interleukin-2:administration & dosage, Kidney Neoplasms:drug therapy, Lymphocyte Count, Male, Mid.   

OBJECTIVES: Recent advances in knowledge of Psychoneuroimmunology have shown that several neuroactive substances, including neurohormones and neuropeptides, may exert immunomodulatory effects. However, despite the great variety of potential neuroimmune interactions, at present we may recognize two major neuroendocrine systems exerting a physiological neuroimmunomodulatory function, consisting of the pineal gland and the brain opioid system, provided by immunostimulatory and immunosuppressive effects, respectively. Recent in human studies have demonstrated the possibility to amplify the biological activity of IL-2, the major anticancer cytokine, by pineal indoles.

MATERIALS & METHODS: The present study was carried out to draw some preliminary in human results on the possible immunomodulatory effects of the inhibition of the brain opioid activity by a long-acting opioid antagonist, naltrexone (NTX). The study was performed in 10 metastatic renal cell cancer patients, who had progressed on a previous immunotherapeutic cycle with IL-2 alone. Patients were treated with the same doses of IL-2 (6 million lU/day subcutaneously for 6 days/week for 4 weeks) plus an oral administration of NTX at a dose of 100 mg every 2 days.

RESULTS: The clinical response consisted of a partial response in 1 and a stable disease in 5 patients, whereas the other 4 patients progressed. Therefore, the percent of non-progressive disease was 6/10 (60%). Moreover, mean lymphocyte increase achieved during IL-2 plus NTX was significantly higher (P<0.05) than that obtained during the previous treatment with IL-2 alone.

CONCLUSIONS: This study shows that a blockade of the brain opioid system, which plays a physiological immunosuppressive role, may improve the anticancer effects of IL-2 in humans....

Read abstract  Full text PDF