Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0007131 (non-small cell lung cancer)
 22,601 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rhizoxin is a 16-membered antifungal macrocyclic lactone isolated from the plant pathogenic fungus Rhizopus chinensis. The compound binds to tubulin, preventing microtubule formation, and inhibiting mitosis. It possesses antitumour activity in vivo against various preclinical murine models, both leukaemias and solid tumours model, as well as in vincristine- and doxorubicin-resistant leukaemia lines. In the present study, cytotoxic activity was observed in human tumour cell lines in vitro at very low concentrations (+/- 10(-10) M) particularly against melanoma, colon, renal, non-small cell and small cell lung cancer. In vivo antitumour activity was demonstrated in murine P388 and L1210 murine leukaemias, solid tumour models B16 melanoma and M5076 sarcoma, and in 5 out of 9 human solid tumour xenografts: LOX melanoma, MX-1 breast cancer, non-small cell lung cancer A549, and small cell lung cancers LXFS 605 and LXFS 650. The absence of cross-resistance to vinca alkaloids was confirmed in vivo against the vincristine-resistant P388 leukaemia subline and the vincristine-resistant human small cell lung cancer LXFS 650. In addition, the antitumour activity of rhizoxin was improved by prolonged or repeated drug administration indicating a schedule dependency. In animal toxicology studies, transient changes in erythrocyte and leukocyte numbers, local phlebitis, diarrhea, and spermatogenic arrest were observed. The LD10 value of rhizoxin after a single intravenous injection was 2.8 mg/kg (8.4 mg/m2). One-tenth of the mouse equivalent LD10 (0.84 mg/m2), the starting dose for clinical phase I studies, was considered to be safe in rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Preclinical antitumour activity and animal toxicology studies of rhizoxin, a novel tubulin-interacting agent. 145 59

The NK activity and ADCC of peripheral blood mononuclear cell were examined to evaluate the contribution of ADCC and NK activity to host immune response against lung cancer. The NK activity and ADCC were examined in 58 patients with primary lung cancer and 40 healthy volunteers as normal controls. The NK activity of patients with lung cancer was significantly subnormal, but ADCC was at a normal level. The NK activity was decreased in non-small cell lung cancer (NSCLC), but not in small cell lung cancer (SCLC) compared to normal controls. According to stage, the NK activity in stage II, III-M0 and III-M1 NSCLC showed low levels compared to that of stage I NSCLC, but there was no difference of NK activity in patients with SCLC. The NK activity was not affected by performance status. There was no significant difference of ADCC in patients with lung cancer according to cell type, stage and performance compared with that of normal controls. The NK activity and ADCC were not changed after chemotherapy and operation respectively.
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PMID:Natural killer activity and antibody-dependent cellular cytotoxicity in patients with primary lung cancer. 150 29

Lung carcinomas represent a heterogeneous group of tumours with large variations in the biochemical, clinical, morphological and pathological manifestations. Despite the neuroendocrine features of small cell lung cancer (SCLC), it is today generally accepted that all types of lung cancer emanate from a common endodermally derived multipotent stem cell of the bronchial epithelium. NCAM (neutral cell adhesion molecule) has been shown to be a sensitive marker of SCLC. The presence of NCAM, with the alpha (2,8) polysialic acid units characteristic of embryonal NCAM, in SCLC and in a portion of NSCLC, seems to correlate with the malignant behaviour and prognosis of the tumours, suggesting that NCAM may have a functional role in the clinicopathological manifestations of lung cancer. Fuc-GM1 with 2-hydroxy fatty acids as a characteristic component of the ceramide has been found to be a unique ganglioside of SCLC, detected in the tissues as well as in serum from SCLC patients using specific monoclonal antibodies. Accumulation of sialylated and fucosylated polylactosamine type 2 carbohydrate glycolipid and glycoprotein antigens was found in serum and tissues of lung tumours in accordance with what is described in gastrointestinal carcinomas, and these antigens may be regarded as general carcinoma antigens irrespective of organ. Sialylated and fucosylated type 1 antigens, and gangliosides with NeuAc alpha (2,6)Gal linkage were also accumulated in lung cancer. The human immune system has been found to recognize lung cancer carbohydrate antigens, which might be human lung cancer autoantigens.
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PMID:Carbohydrate antigens in human lung carcinomas. 152 May 24

A prospective study to compare the safety and diagnostic accuracy of ultrasonographically guided transthoracic large-bore cutting biopsy histologic examination with fine-needle aspiration cytologic examination was conducted in 149 patients with thoracic tumors (29 mediastinal tumors and 120 pulmonary masses). The authors found that large-bore cutting biopsy under ultrasonographic guidance could be as safe as fine-needle aspiration, whereas diagnostic accuracy was significantly higher (97% versus 59% in malignant tumors, respectively, P less than 0.05; 85% versus 33% in benign lesions, respectively, P less than 0.05). The size, depth, and location of lesions did not influence the results of transthoracic needle aspiration or cutting biopsy. In 77 patients with primary lung cancer, fine-needle aspiration cytologic examination, although achieving 88% positive cytologic results, identified the histologic cell type accurately in only 70%, whereas Tru-Cut (Top Surgical, Tokyo, Japan) biopsy was 97% accurate in confirmative histologic diagnosis. Fourteen patients had discordant cytologic and histologic diagnoses, and the cases of 3 (3.9%) were between small cell lung cancer and non-small cell lung cancer. The diagnostic accuracy of Tru-Cut biopsy also was significantly higher than that of fine-needle aspiration in metastatic cancers (90% versus 33%, respectively) and mediastinal tumors (100% versus 46%, respectively). The authors conclude that transthoracic cutting biopsy under ultrasonographic guidance is safe and has a higher diagnostic accuracy as compared with fine-needle aspiration. This technique is particularly useful for benign lesions or tumors with pleomorphic morphologic characteristics, such as lymphomas and thymomas.
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PMID:Ultrasonographically guided biopsy of thoracic tumors. A comparison of large-bore cutting biopsy with fine-needle aspiration. 156 79

Small cell lung cancer (SCLC) manifests a number of neuroendocrine differentiation features and antigenic characteristics that distinguish the tumour from non-small cell lung cancer (NSCLC). Several surface antigens on SCLC cells, identified by clusters of monoclonal antibodies (MAbs), distinguish SCLC and other neuroendocrine tumours of NSCLC. Stable transfection of the c-myc proto-oncogene has been reported to confer upon classic SCLC cells the growth properties and morphology of the variant subtype of SCLC (SCLC-v). Furthermore, insertion of the v-Ha-ras oncogene into such SCLC-v cells has been found to induce features typical of NSCLC. We have used classic SCLC cells transfected with c-myc, or co-transformed with c-myc and v-Ha-ras, to examine the expression of characteristics SCLC cluster antigens. Flow cytometric assays reveal that SCLC cells co-transformed with c-myc and v-Ha-ras oncogenes down-modulate SC-1, SC-2 and SC-5A surface antigens to levels approaching, in some cases, those seen with NSCLC cells. The SC-4 surface antigen is not modulated by activation of these oncogenes. These findings support clinical and laboratory observations that important transitions can occur between subtypes of human lung cancer cells, and that these shifts may play a role in the clinical progression of lung cancer.
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PMID:Modulation of neuroendocrine surface antigens in oncogene-activated small cell lung cancer lines. 164 69

We assayed the panel of SCLC MAbs using multi-tissue tumour block (MTTB) slides obtained from Dr. Hector Battifora (City of Hope Hospital, Duarte CA). MTTB slides contain up to 100 different formalin-fixed tumour tissue specimens and can be immunostained with as little as 50 microliters of antibody solution. In this study, the MAbs in the SCLC panel were used to stain slides from a MTTB comprised of eight normal, ten SCLC, ten squamous cell, ten adenocarcinoma and five undifferentiated lung cancer tissues. Many MAbs in the SCLC panel failed to immunostain the lung MTTB whereas many others showed significant immunoreactivity. Of those MAbs that stained SCLC tissue, none was found to be specific; these MAbs also stained NSCLC tissues or normal lung tissues. Some MAbs in the panel immunostained SCLC and NSCLC tissues, but were also reactive to normal lung tissue as well as other normal tissue specimens. A major advantage of immunostaining MTTBs with a panel of MAbs is that we were able to compare the immunoreactivity of the MAbs on a total of 128 different tissues requiring only 100 microliters of antibody solution using only two MTTB slides per MAb. Although this study was preliminary and certain technical problems in assembling the MTTB as well as optimising the immunostaining procedure for handling 98 or more MAbs simultaneously remain, the MTTB technique remains promising.
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PMID:Cross validation of cluster analysis using immunostained multi-tissue tumour block slides. 164 74

This review addresses means for the improvement of treatment results in small cell and non-small cell lung cancer. In small cell lung cancer prognostic factors such as the distinction between classic and variant type in vivo remain an important subject for further investigations. Data concerning the schedule dependency of etoposide will lead to the investigation of new treatment regimens. The effect of warfarin is intriguing and warrants further research. Investigations of the damaging effects of prophylactic brain irradiation versus the effect on survival should be awaited before the role of prophylactic brain irradiation can be defined. The role of radiotherapy in the improvement of survival of limited-disease patients remains controversial. In non-small cell lung cancer the role of both radiotherapy and chemotherapy is still a matter of a seemingly never-ending debate. A major problem is the selection of patients. Therefore only randomized phase III trials should be performed in carefully defined subgroups of patients, based upon stage, performance status, and presence or absence of symptoms.
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PMID:Management of non-small cell and small cell lung cancer. 164 72

The present study examines the relationship between neuroendocrine (NE) differentiation and the clinical behaviour of non-small cell lung cancer (NSCLC). Retrospective (n = 315) and prospective (n = 44) cohorts of non-small cell tumours were obtained from surgically treated cases of lung cancer, comprising 218 squamous cell carcinomas, 65 adenocarcinomas, 51 adenosquamous carcinomas, and 25 large cell undifferentiated carcinomas. Paraffin wax embedded and fresh frozen tissue sections were stained for the NE markers neurone specific enolase, creatine kinase-BB, bombesin, neurotensin, chromogranin A, synaptophysin and UJ-13A. The expression of two or more markers was observed in 30% of cases, and was taken to identify NE-NSCLC. A statistically significant correlation between nodal status and NE differentiation (P = 0.05), and disease stage and NE differentiation (P = 0.04) was observed. However, there was no correlation between NE differentiation and survival. These findings suggest that NE-NSCLC, analogous to SCLC is more highly metastatic than non-NE-NSCLC.
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PMID:Neuroendocrine differentiation and clinical behaviour in non-small cell lung tumours. 165 75

The p53 gene has been implicated as a tumor-suppressor gene whose disruption is involved in the pathogenesis of common human cancers. The results of extensive analysis of p53 mutations in non-small cell lung cancers (NSCLCs) have revealed that p53 is mutated in 45% of NSCLC with base changes different from those of colon cancer. In this study, we examined 17 SCLC tumor samples taken directly from 15 patients as well as the corresponding nine tumor cell lines. Mutations changing the p53 coding sequence were found in 11 of 15 patients (73.3%) and showed a similar but distinct nucleotide substitution pattern compared with NSCLC, suggesting that a different mutagenic process is involved. In addition, a strong correlation was seen between the presence of p53 mutations in tumors and the successful establishment of the corresponding cell lines, suggesting that p53 mutations can confer a selective growth advantage in vitro (and probably also in vivo).
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PMID:The p53 gene is very frequently mutated in small-cell lung cancer with a distinct nucleotide substitution pattern. 165 62

Twelve inoperable lung cancer patients were treated with a combination chemotherapy of cisplatinum (CDDP) and etoposide (VP16), as a continuous infusion for 5 days, every 21 days, and with a daily oral administration of GaCl3. Dosages of CDDP and VP16 were adapted in order to obtain an area under the curve (AUC) of 80,000 micrograms l-1.h for plasma total platinum and of 200 mumol.l-1 h for plasma VP16 during each 120 h infusion. GaCl3 was given at the dosage of 400 mg/24h from the time of diagnosis at least until the evaluation after 3 courses of chemotherapy. An objective response was observed in 5 non small cell (NSCLC) lung cancer patients (group 1) and 3 small cell (SCLC) lung cancer patients (group 2). In the other 4 patients with a NSCLC no partial response was noted (group 3). No significant difference in area under the curve (AUC) was noted between the 3 groups, either for plasma total platinum (group 1 = 89,598 +/- 20,843 micrograms l-1.h; group 2 = 88,081 +/- 15,431 micrograms l-1.h; group 3 = 83,820 +/- 13,455 micrograms l-1.h), or for VP16 (group 1 = 227 +/- 41 mumol.l-1 h; group 2 = 217 +/- 29 mumol.l-1.h and group 3 = 211 +/- 30 mumol.l-1.h). The maximal plasma Ga concentrations were 244 +/- 34 micrograms/l in group 1, 112 +/- 57 micrograms/l in group 3 (p less than 0.005) and 243 +/- 132 micrograms/l in group 2. It was then decided to increase the dose of GaCl3 in the further non-responding patients. In 6 responders, 3 additional courses of this combination chemotherapy could have been given without major toxicity, allowing a much more important decrease in the tumor volume in 4 of them. This schedule of treatment should permit the chemotherapy to continue for longer than 6 courses, in order to improve the survival time.
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PMID:Combination chemotherapy with cisplatin, etoposide and gallium chloride for lung cancer: individual adaptation of doses. 166 Jun 90


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