Severe muscle weakness due to hypokalemia as a manifestation of small-cell carcinoma.
(33/2496)
We describe the case of a 56-year-old man with severe muscle weakness due to heavy hypokalemia (serum potassium 1.44 mmol/l) associated with inappropriate kaliuria and alkalemia. Subsequent investigation revealed the presence of ectopic ACTH hypersecretion due to a small-cell lung carcinoma. A significant clinical/laboratory improvement was achieved following chemotherapy-induced regression of the primary tumor. The profound hypokalemia was probably the result of cortisol hypersecretion, which in concert with the ACTH-induced decreased 11beta-hydroxysteroid dehydrogenase activity can exhibit an increased mineralocorticoid activity. In addition, other ACTH-dependent mineralocorticoids may play a contributory role in the development of severe hypokalemia. (+info)
Sigma receptor photolabeling and sigma receptor-mediated modulation of potassium channels in tumor cells.
(34/2496)
Recent work has indicated that sigma receptor ligands can modulate potassium channels. However, the only sigma receptor characterized at the molecular level has a novel structure unlike any other receptor known to modulate ion channels. This 26-kDa protein has a hydropathy profile suggestive of a single membrane-spanning domain, with no apparent regions capable of G-protein activation or protein phosphorylation. In the present study patch clamp techniques and photoaffinity labeling were used in DMS-114 cells (a tumor cell line known to express sigma receptors) to investigate the role of the 26-kDa protein in ion channel modulation and probe the mechanism of signal transduction. The sigma receptor ligands N-allylnormetazocine (SKF10047), ditolylguanidine, and (+/-)-2-(N-phenylethyl-N-propyl)-amino-5-hydroxytetralin all inhibited voltage-activated potassium current (IK). Iodoazidococaine (IAC), a high affinity sigma receptor photoprobe, produced a similar inhibition in IK, and when cell homogenates were illuminated in the presence of IAC, a protein with a molecular mass of 26 kDa was covalently labeled. Photolabeling of this protein by IAC was inhibited by SKF10047 with half-maximal effect at 7 microM. SKF10047 also inhibited IK with a similar EC50 (14 microM). Thus, physiological responses to sigma receptor ligands are mediated by a protein with the same molecular weight as the cloned sigma receptor. This indicates that ion channel modulation is indeed mediated by this novel protein. Physiological responses were the same when cells were perfused internally with either guanosine 5'-O-(2-thiodiphosphate) or GTP, indicating that signal transduction is independent of G-proteins. These results demonstrate that ion channels can be modulated by a receptor that does not have seven membrane-spanning domains and does not employ G-proteins. Sigma receptors thus modulate ion channels by a novel transduction mechanism. (+info)
Long survival of patients with small cell lung cancer after adjuvant treatment with the anti-idiotypic antibody BEC2 plus Bacillus Calmette-Guerin.
(35/2496)
Despite active therapies for small cell lung cancer (SCLC), most patients relapse and die of the disease. The present study evaluates immunization using the anti-idiotypic antibody BEC2, which mimics the ganglioside GD3 expressed on the surface of most SCLC tumors, combined with Bacillus Calmette-Guerin (BCG) as an immune adjuvant. We hypothesized that active immunization could alter the natural history of the disease. Fifteen patients who had completed standard therapy for SCLC received a series of five intradermal immunizations consisting of 2.5 mg of BEC2 plus BCG over a 10-week period. Blood was collected for serological analysis, and outcome was monitored. All patients developed anti-BEC2 antibodies, despite having received chemotherapy with or without thoracic radiation. We detected anti-GD3 antibodies in five patients, including those with the longest relapse-free survival. The median relapse-free survival for patients with extensive stage disease is 11 months and has not been reached for patients with limited stage disease (>47 months), with only one of seven patients having relapsed after a median follow-up of 47 months. Immunization of patients with SCLC after standard therapy using BEC2 plus BCG can induce anti-GD3 antibodies and is safe. The survival and relapse-free survival in this group of patients are substantially better than those observed in a prior group of similar patients. A Phase III trial is being conducted to evaluate BEC2 plus BCG as adjuvant therapy after chemotherapy and irradiation. (+info)
Vasospastic angina likely related to cisplatin-containing chemotherapy and thoracic irradiation for lung cancer.
(36/2496)
Vasospastic angina is rarely observed during cancer treatment. The present report describes two males with lung cancer, aged 73 and 61, who developed vasospastic angina during combination treatment of cisplatin-containing chemotherapy and thoracic irradiation. As both patients have smoked and their ages are typical for patients with coronary artery disease, such events may be incidental. However, oncologists should be aware of the possible development of myocardial ischemia during or following administration of antineoplastic agents, especially in elderly patients with pre-existing coronary risk factors or a history of thoracic radiotherapy. (+info)
Four cases of therapy-related leukemia.
(37/2496)
Combination chemotherapy and radiation therapy have contributed to the successful treatment of various cancer patients. But the development of second malignancies is an inevitable complication of long-term cytotoxic treatment. The most serious and frequent of such complications is acute myelogenous leukemia (AML). Therapy-related leukemia is generally fatal. Since the number of patients exposed to chemotherapy is increasing each year, the clinical significance of this entity cannot be underestimated. There have been many investigations of therapy-related leukemia, but in Korea published reports are rare. We describe four such cases, involving one older female with lung cancer and three children with acute lymphoblastic leukemia (ALL) and malignant lymphoma. Alkylating agents were used for chemotherapy, and in one case, topoisomerase II inhibitor. Irrespective of the causative agents, the latency periods were relatively short, and despite induction chemotherapy in two, all survived for only a few months. During the follow-up of patients treated for primary malignancies, the possibility of therapy-related leukemia should always be borne in mind. (+info)
Two-step targeting and dosimetry for small cell lung cancer xenograft with anti-NCAM/antihistamine bispecific antibody and radioiodinated bivalent hapten.
(38/2496)
The "affinity enhancement system," a two-step targeting technique using bispecific antibody and radiolabeled bivalent hapten, has been reported to be useful for carcinoembryonic antigen-expressing tumors. The purpose of this study was to evaluate the efficacy of this method for targeting human small cell lung cancer using an antineural cell adhesion molecule antibody. METHODS: Antineural cell adhesion molecule/antihistamine bispecific antibody NK1NBL1-679 was prepared by coupling an equimolecular quantity of a Fab' fragment of NK1NBL1 to a Fab fragment of antihistamine 679. Athymic mice inoculated with NCI-H69 small cell lung cancer cells expressing neural cell adhesion molecule were administered bispecific antibody and then 48 h later 125I-labeled bivalent histamine hapten. 125I-labeled intact NK1NBL1 was injected into other groups of mice. Biodistributions were examined as a function of time. RESULTS: In mice of the two-step targeting, tumor uptake was 2.5 +/- 0.2, 3.2 +/- 0.4, 6.4 +/- 2.0, 7.2 +/- 2.7, 6.1 +/- 2.1 and 2.2 +/- 0.4 %ID/g at 5, 30 min, 5, 24, 48 and 96 h, and tumor-to-blood, tumor-to-liver and tumor-to-kidney ratios were 1.4 +/- 1.1, 10.8 +/- 13.2 and 4.6 +/- 4.7, respectively, at 5 h, whereas 125I-labeled NK1NBL1 showed a tumor uptake of 5.7 +/- 0.4 %ID/g and tumor-to-blood, tumor-to-liver and tumor-to-kidney ratios of 0.3 +/- 0.1, 1.1 +/- 0.2 and 0.9 +/- 0.1, respectively, at 5 h. These results were confirmed by autoradiographic studies, which demonstrated clear tumor-to-normal tissue contrast. Dosimetry showed that the affinity enhancement system could enhance the therapeutic potential of the antineural cell adhesion molecule antibody NK1NBL1. CONCLUSION: This two-step targeting method seems promising for the diagnosis and therapy of small cell lung cancer. (+info)
The expression of p73 is increased in lung cancer, independent of p53 gene alteration.
(39/2496)
p73 gene, a new p53 homologue, has been identified: it supposedly acts as tumour suppressor gene in neuroblastoma. To clarify whether p73 might be involved in lung carcinogenesis, we examined p73 expression in resected lung cancer and paired normal lung in 60 cases using semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR). We also examined p73 gene status in three representative cases using Southern blot, and p53 gene alteration in 49 cases using PCR-single-strand conformation polymorphism (PCR-SSCP) and direct sequence. In 87% of the cases (52/60) p73 expression in tumour was more than twice as high as that in paired normal lung tissues, and the difference between p73 expression in tumour and normal lung tissue was significant (P < 0.0001). However, Southern blot analysis revealed that none of the cases showed p73 gene amplification. Compared with clinicopathological characteristics, p73 expression correlates significantly with histological differences and age of patient, independently (P < 0.05). Concerning p53 gene status, 43% (21/49) showed p53 gene alteration, but there was no correlation between p73 overexpression and p53 gene alteration. Our results suggest that need for further functional analysis of the role of p73 in lung carcinogenesis. (+info)
Epoetin alpha prevents anaemia and reduces transfusion requirements in patients undergoing primarily platinum-based chemotherapy for small cell lung cancer.
(40/2496)
Anaemia commonly occurs in cancer patients receiving chemotherapy, often necessitating blood transfusion. This multicentre study was designed to evaluate the efficacy and safety of epoetin alpha in preventing the decline in haemoglobin (Hb) level, and to determine whether the transfusion requirement could be reduced, in patients receiving 4-6 cycles of primarily platinum-based combination cyclic chemotherapy for small cell lung cancer (SCLC). A total of 130 non-anaemic SCLC patients were randomized to receive no additional treatment (n = 44), epoetin alpha 150 IU kg(-1) subcutaneously (s.c.) three times a week (n = 42) or 300 IU kg(-1) s.c. three times a week (n = 44). Reductions in epoetin alpha dosage were made during the study if Hb level increased to >15 g dl(-1). The mean weekly dosage was 335 and 612 IU kg(-1), respectively, in the two active treatment groups. Significantly fewer (P < 0.05) epoetin alpha-treated patients experienced anaemia (Hb < 10 g dl(-1)) during the course of chemotherapy (300 IU kg(-1), 39%; 150 IU kg(-1), 48%; untreated, 66%). This was reflected in the significantly lower number of treated patients transfused [300 IU kg(-1), 20% (P< 0.001); 150 IU kg(-1), 45% (P< 0.05); untreated, 59%]. Epoetin alpha was well-tolerated, and there was no evidence of sustained, clinically significant, hypertension. In summary, epoetin alpha is effective and well-tolerated in maintaining Hb level and reducing transfusion requirement in patients undergoing cyclic chemotherapy for SCLC. (+info)