Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0149925 (small cell lung cancer)
 6,491 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has been demonstrated that antitumor immune response is an IL-2-dependent phenomenon. Moreover, experimental results suggest the existence of interactions between IL-2 and the pineal gland, which also plays a role in the control of immunity and cancer growth. Alterations of both IL-2 and melatonin secretion have been reported in cancer patients. To further investigate pineal/IL-2 relationships in humans with cancer, we evaluated the melatonin rhythm in seven advanced small cell lung cancer patients, before and at weekly intervals during immunotherapy with IL-2, given subcutaneously at a daily dose of 3 x 10(6) IU/m2 twice daily for 5 days/week for 4 weeks. Before IL-2, no patient showed a light/dark rhythm of melatonin. IL-2 administration induced a normalization of the melatonin circadian rhythm, with the appearance of a night time peak in 4/7 patients. This effect, however, disappeared with IL-2 interruption in 3/4 patients. This preliminary study, by showing that IL-2 may restore a normal melatonin rhythm, suggests that the anomalous pineal function in cancer may depend at least in part on the altered endogenous IL-2 production.
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PMID:Normalization of the light/dark rhythm of melatonin after prolonged subcutaneous administration of interleukin-2 in advanced small cell lung cancer patients. 132 6

A total of 184 patients with small cell lung cancer (SCLC) including 18 patients with ipsilateral pleural effusion as the only evidence of metastasis beyond the primary tumor site (PL), 84 patients with limited disease (LD), and 82 patients with extensive disease (ED) were treated at the Osaka Prefectural Habikino Hospital between December 1982 and June 1990. The median survival time for patients with PL was 51 weeks; for the patients with LD, 51 weeks; and for the patients with ED, 34 weeks. The survival of PL patients was significantly better than that of ED patients (P less than 0.05), and did not differ from that of LD patients. The response rate of PL patients was not significantly different from the response rates observed in LD- and ED-patients. There was no significant difference in survival or response rate between patients with cytologically positive and those with cytologically negative PL. Ipsilateral pleural effusion was not found to be a independent prognostic factor for survival from multivariate analysis in LD patients. These results indicate that the classification of limited disease small cell lung cancer should include patients with ipsilateral pleural effusion, as suggested by the consensus report at the International Association for the Study of Lung Cancer (IASLC) Workshop in 1989.
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PMID:[Prognosis of small cell lung cancer with ipsilateral pleural effusion]. 132 75

Locally advanced lung cancer carries a poor prognosis, and its treatment continues to challenge medical, radiation, and surgical oncologists. While systemic chemotherapy has improved the survival of patients with small cell lung cancer (SCLC), the role and timing of thoracic radiotherapy has not been clearly defined. The roles of chemotherapy and radiotherapy appear to be reversed in the treatment of locally advanced non-small cell lung cancer (NSCLC). The routine use of thoracic radiotherapy has been shown to improve local control after surgery without affecting survival, due to a high incidence of distant metastases. This contrasts with the marginal survival benefit seen with chemotherapy in NSCLC. Nevertheless, the results of recent clinical trials in both SCLC and NSCLC are encouraging and support continued investigation. These studies and the results of recent pilot studies suggest that a closer integration of chemotherapy and radiotherapy (concomitant chemoradiotherapy) may be necessary for further improvement in outcome. This review will present the results of recent studies in systemic therapy of lung cancer and the evidence supporting concomitant chemoradiotherapeutic treatment of this disease.
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PMID:The evolving role of systemic therapy in carcinoma of the lung. 132 27

The role of surgery in the treatment of small cell lung cancer remains a subject of debate. We carried out a retrospective review of 87 patients with small cell lung cancer referred to one surgeon for staging and treatment. Thirty patients (34.5%) were deemed suitable for thoracotomy. Fourteen patients had stage I disease, 5 patients had stage II disease, and 11 patients had stage III disease. Twenty-eight of the 30 patients (93.3%) went on to have surgical resection. The actual overall 5-year survival in all patients who underwent thoracotomy was 43.3%. The actual 5-year survival for patients in stages I and III was 57.1% and 55.5%, respectively. No patients with stage II disease survived 5 years. We conclude that there is a small group of patients with small cell lung cancer in whom, with careful preoperative staging, the prospects of cure by operation are similar to those with non-small lung cancer.
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PMID:Results of operation without adjuvant therapy in the treatment of small cell lung cancer. 132 56

We performed a 3-armed phase III study between 1982 and 1990 to evaluate low dose natural interferon alfa (nIFN-alpha) as a maintenance therapy in small cell lung cancer (SCLC) following induction chemotherapy (CT) and consolidation radiotherapy (RT). All patients received four cycles of CT (cyclophosphamide, vincristine, etoposide), followed by split-course RT (55 Gy in 20 fractions over 7 weeks). 410 patients entered the study. 237 patients who completed induction CT + RT and were classified as responders (complete response + partial response) were randomly assigned to arm 1: low dose nIFN-alpha (91 patients); arm 2: maintenance CT, six cycles of CAP (cyclophosphamide, doxorubicin, cisplatin) (59 patients); or arm 3: control arm (no maintenance treatment) (87 patients). Halfway through the study the CAP arm was discontinued. There was no difference in median survival between the groups (IFN: 11 months, CAP: 11 months, control: 10 months), but a clear difference in long-term survival and in survival in the limited disease group, favouring nIFN-alpha maintenance therapy. Proportional hazards regression analysis also showed a significant effect of IFN treatment on survival. Our results suggest a role for nIFN-alpha in maintaining a clinically disease-free status achieved with other treatment modalities.
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PMID:Natural interferon alfa as maintenance therapy for small cell lung cancer. 132 76

Gastrin releasing peptide (GRP), the human homologue of bombesin (BN), is an autocrine growth factor for small cell lung cancer (SCLC) cells. The synthetic octapeptides [D-cpa1-beta-Leu8-des-Met9]litorin (BIM 26182) and [D-Phe6-Leu13-CH2NH-Cpa14]bombesin(6-14)NH2 (BIM 26189) are potent GRP/BN antagonists of the proliferation of 3T3 and rat pancreas cells. The effect of these analogues on the proliferation of four SCLC cell lines (SCLC 6, SCLC 41, SCLC 75, SCLC 74R) was tested in vitro and in vivo. Two of these SCLC lines (SCLC 41M and SCLC 75) had receptors for BN/GRP and expressed the prepro-GRP mRNA. BIM 26182 and BIM 26189 inhibited [3H]thymidine incorporation into the DNA of SCLC 41 cells, stimulated [3H]thymidine incorporation in SCLC 6, and had no effect on the two other cell lines. The SCLC implanted s.c. in nude mice were treated with either BIM 26182 or BIM 26189. BIM 26182 and BIM 26189 injected at the doses of 50 micrograms twice a day (s.c.) around the tumor for 10 to 21 days delayed the growth of SCLC 41 and of SCLC 75. The maximal effect was observed during the treatment period, after which the tumors regrew, suggesting a cytostatic effect of these peptides. No inhibitory effect of the peptides on SCLC 74R or SCLC 6 growth was observed. These data suggest that GRP antagonists are able to inhibit the in vitro and in vivo growth of BN/GRP receptors-positive SCLC.
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PMID:Antitumoral activity of bombesin analogues on small cell lung cancer xenografts: relationship with bombesin receptor expression. 132 85

A ricin A chain immunotoxin, SEN36-ricin A chain, directed against the neural cell adhesion molecule (N-CAM) had no selective cytotoxic activity against three different small cell lung cancer (SCLC) cell lines in tissue culture despite expression of the target antigen on more than 98% of cells in each line detected by indirect immunofluorescence. Treatment of the SW2 SCLC cell line with suramin and interferons alpha and gamma increased the level of N-CAM expression only slightly and had no significant effect on the cytotoxic activity of the SEN36 immunotoxin. In the presence of the carboxylic ionophore monensin at a concentration of 0.1 microM, the toxicity of SEN36-ricin A chain to the SW2 cell line was enhanced by 12,000-fold. In contrast, lysosomotropic amines showed little or no potentiation of activity, suggesting that lysosomal degradation was not the major factor limiting the action of the anti-N-CAM immunotoxin. The findings of this study indicate that ricin A chain immunotoxins directed against N-CAM on SCLC are unlikely to have sufficient activity to be useful therapeutic agents in the absence of potentiating agents such as monensin, which can interfere with the normal intracellular pathways of antigen routing.
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PMID:Potentiation of a weakly active ricin A chain immunotoxin recognizing the neural cell adhesion molecule. 132 2

Three cell lines of small cell lung cancer (SCLC), which were established from specimens of untreated primary tumors biopsied by diagnostic bronchofiberscopy, were analyzed for immunological characteristics. These cell lines showed considerable heterogeneity in chemo-radiosensitivity, which was well correlated with clinical responses of the respective tumors, but their HLA-class I antigen expressions were equally depressed and they were susceptible to peripheral blood lymphocytes (PBL) and lymphokine-activated killer (LAK) cells, irrespective of their diverse chemo-radiosensitivity. Treatment of the cell lines with recombinant immune interferon (rIFN-gamma) increased their HLA-class I antigen expression and conversely depressed PBL sensitivity but not LAK sensitivity. This inverse relationship between HLA-class I expression and PBL susceptibility was also demonstrated using other pairs of autologous PBL and SCLC cell lines. rIFN-gamma changed neither HLA-class II antigen nor SCLC-specific antigen expression under the same experimental conditions. In vitro immunization of allogeneic peripheral blood lymphocytes with rIFN-gamma-treated SCLC cells induced allo-specific killer cells which lysed rIFN-gamma-treated more strongly than non-treated SCLC cells. These results suggest that reduced HLA-class I antigen expression of SCLC could protect the cancer from attack of killer T cells in spite of the higher sensitivity to PBL or LAK cells.
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PMID:High sensitivity to peripheral blood lymphocytes and low HLA-class I antigen expression of small cell lung cancer cell lines with diverse chemo-radiosensitivity. 132 31

This article describes the current approach to the systematic management of both small cell and non-small cell lung cancer (NSCLC). The treatment of stages I, II, and IIIa NSCLC is surgical resection. Although adjuvant chemotherapy in stage I disease offers no survival benefit, the role of adjuvant chemotherapy in stage II and IIIa NSCLC remains controversial. Results of pilot studies using neoadjuvant chemotherapy in stage IIIa NSCLC are encouraging and data from ongoing randomized trials are awaited with interest. For locally advanced NSCLC, chest irradiation remains the standard of care. However, the addition of systemic chemotherapy holds promise. The impact of cisplatin-based regimens on overall survival in stage IV NSCLC remains disappointing. The introduction of newer agents, such as 7-ethyl-10-[4-(1-piperidino)-1-piperidino] carbonyloxycamptothecin (CPT-11), a topoisomerase-I inhibitor, has shown early favorable results. Chemotherapy is the most important therapeutic modality in the management of small cell lung cancer because of this cancer's propensity for early dissemination. In limited stage small cell lung cancer, chest radiotherapy, particularly if used early and concurrently with chemotherapy, may improve survival, but at the expense of increased toxicity. The role of prophylactic brain irradiation remains controversial in limited-stage disease. Chemotherapy is also the most important treatment modality in extensive-stage disease, but its role is only palliative. Radiotherapy is reserved primarily for disease-related complications in patients in whom chemotherapy has failed.
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PMID:Lung cancer: a review of current therapeutic modalities. 132 79

The cytotoxic activity profile of an immunotoxin, SWA11-ricin A chain, recognising a cell-surface antigen associated with human small cell lung cancer (SCLC), was examined in detail using a panel of SCLC, non-SCLC and non lung tumour cell lines in tissue culture. SWA11-ricin A chain was potently and selectively active against three SCLC cell lines of both classic and variant morphologies, inhibiting the incorporation of 3H-leucine with an IC50 of 5 x 10(-11) M. At a concentration of 1 x 10(-8) M, the SWA11 immunotoxin could selectively eliminate in excess of 99.9% of clonogenic tumour cells. Intoxication proceeded rapidly following a 4 h lag phase; the initial rate of protein synthesis inhibition occurred with a t50 of 2 h and a t10 of 7 h. The cytotoxic activity of SWA11-ricin A chain was potentiated by 100-fold in the presence of the carboxylic ionophore monensin at 1 x 10(-7) M. Kinetic studies revealed that monensin enhanced the rate of protein synthesis inhibition by two-fold and eliminated the lag phase suggesting a rapid effect on either the rate or route of internalisation. Studies with SWA11 could detect no influence of monensin on the rate of antibody internalisation and a transient delay in the delivery of internalised antibody to lysosomes was observed by immunoelectron microscopy.
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PMID:Potent cytotoxic action of the immunotoxin SWA11-ricin A chain against human small cell lung cancer cell lines. 132 25


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