Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human calcitonin (CT) gene transcription is regulated by proximal 5' flanking sequences which mediate cAMP-induced expression, and by a distal basal enhancer region. Using transient expression of CT-CAT constructs, we showed that the basal enhancer is active in a CT-producing small cell lung cancer cell line (DMS53) and the thyroid C cell derived tumor line, TT, but is inactive in non-CT-producing cell lines. In deletional and direct mutational analyses of the distal enhancer region, disruption of two elements resembling recognition sequences for the helix-loop-helix (HLH) family of transcriptional regulatory proteins resulted in a significant loss of basal transcriptional enhancer action. These results suggest that HLH recognition motifs may mediate a significant portion of constitutive CT gene transcriptional activity in these cells. Nuclear protein extracts from DMS53 cells formed specific binding complexes with oligonucleotides containing two of these candidate enhancer sequences. However, proteins capable of binding to these CT gene HLH consensus recognition sites were not restricted to CT-producing cells. We conclude that members of the HLH protein family, some expressed ubiquitously and some expressed or activated in a tissue-restricted fashion, may combine to enhance CT gene transcription in tumor cells of neuroendocrine derivation.
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PMID:Human calcitonin gene regulation by helix-loop-helix recognition sequences. 173 89

Beta-endorphin-like immunoreactivity (beta-ELIR) blood levels in control subjects and in patients with different carcinoma and non-Hodgkin's lymphoma tumor types, were found within the same range, with the exception of one carcinoma type. This pertained to a group of patients with small cell lung cancer who had a significantly higher median beta-ELIR level compared to controls. This finding, and the fact that proopiomelanocortin expression is enhanced in tissues of this cancer type, suggest that the latter might secrete elevated beta-ELIR amounts into the blood of the affected patients.
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PMID:Beta-endorphin-like immunoreactivity: assessment of blood levels in patients with tumors of different origin. 180 94

Etoposide is one of the few cancer chemotherapy agents that is schedule-dependent in both preclinical and clinical studies. A randomized trial of etoposide as initial therapy in extensive small cell lung cancer (SCLC) demonstrated the superiority of a 5-day course versus the same total dose administered over 24 hours. The recent availability of oral etoposide capsules has led to further exploration of etoposide's schedule-dependency through the use of daily oral etoposide. Initially, studies at Indiana University and the Hoosier Oncology Group concentrated on refractory germ cell tumors and refractory SCLC. Although both of these tumor types are sensitive to etoposide combination chemotherapy as initial treatment, it is rare to see a response with any single agent in refractory disease. In 25 patients with refractory germ cell tumors, we observed 5 objective responses (20%). In addition, 3 other patients (12%) clearly achieved antitumor effect with a greater than 90% reduction in tumor markers, although radiographic findings remained stable. In refractory SCLC, 1 complete and 5 partial responses were observed in 26 patients, for a 23% response rate. Twenty-five of the 26 had received prior cisplatin/etoposide and 14 also had received prior cyclophosphamide/doxorubicin/vincristine. Daily oral etoposide is capable of producing palliation and objective responses in heavily pretreated patients and may be a preferable method of administration. Future trials are planned using daily oral etoposide as a component of combination chemotherapy as first- and second-line therapy in patients with SCLC.
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PMID:Daily oral etoposide in the treatment of cancer. 184 80

A 57-Year-old male with small cell lung cancer had been treated by cisplatin and etoposide. After these chemotherapies he relapsed with the primary site and multiple brain metastases followed by chest irradiation (50 GY) and cranial radiotherapy (40 GY). Though these sites were regressive, abdominal tumor was detected. So, abdominal CT showed multiple retroperitoneal lymphnode swellings and abdominal wall involvement without liver metastasis. After cisplatin and etoposide were administered intravenously, he was treated with etoposide (150 mg/body days 1-4) orally every month. Retroperitoneal lymphnode swellings were remarkably regressed with oral administration of etoposide. It is conceivable that etoposide is one of the useful salvage chemotherapies of relapsed small cell lung cancer, even treated orally.
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PMID:[A case of remission of multiple retroperitoneal lymph node relapse in small cell lung cancer treated with oral etoposide]. 184 31

We studied 107 specimens (38 tumors and 69 tumor cell lines) from 90 patients with small cell lung cancer to determine the characteristics and clinical situations of patients from whom tumor cell lines could be established and the myc family DNA copy number. The proportion of extensive stage small cell lung cancer patients from whom a tumor cell line could be established prior to the initiation of therapy increased during the 10 years of the study (P less than 0.001). Amplification of one of the myc family genes occurred in 3 of 40 (8%) of the untreated patient specimens compared to 19 of 67 (28%) of the treated patient specimens (P = 0.01). The myc family DNA amplification occurred in 17 of 54 (31%) of the specimens from patients treated with cyclophosphamide-based combinations and 2 of 13 (15%) of the specimens from patients treated with etoposide/cisplatin (P = 0.25). Both tumors and tumor cell lines were obtained from 17 patients with small cell lung cancer and the myc family DNA copy number was similar in 16 of the 17 patients. We conclude that: (a) myc family DNA amplification occurs more commonly in specimens from treated than untreated patients (b) there are no prominent differences in the frequency of amplification following treatment with different chemotherapy regimens; and (c) myc family DNA amplification is similar in tumors and tumor cell lines from the same patients.
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PMID:myc family DNA amplification in 107 tumors and tumor cell lines from patients with small cell lung cancer treated with different combination chemotherapy regimens. 184 42

A long survival case of small cell lung cancer synchronized with renal cancer was reported. The patient was a 73-year-old male, complaining of cough and fever up. The chest roentgenogram showed a tumor mass in the right lower lung field. The specimen obtained from transbronchial lung biopsy of right S8b was diagnosed as small cell carcinoma of lung. In the check of the metastasis to other organs, abdominal CT scanning and the echogram demonstrated a solitary mass in the left kidney. We supposed a possibility of primary renal cancer rather than the metastasis from the lung because of being solitary mass, no existence of the metastasis except the kidney, and from the finding of the renal angiography. The patient underwent left nephrectomy for the renal cancer, and also underwent right lower lobectomy for the lung cancer after neo-adjuvant chemotherapy using cisplatinum and carboquone. Pathologically, the renal lesion was diagnosed as typical clear cell carcinoma of the kidney. He has survived for more than 4 years.
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PMID:[A long survival case of small cell lung cancer synchronized with renal cancer]. 185 Apr 90

An analysis of the chest recurrences was conducted in 72 consecutive patients with limited small cell lung cancer treated in two successive phase II trials alternating six induction chemotherapy courses and three series of thoracic radiotherapy, followed by maintenance chemotherapy. The total radiation dose was 45 Gy (3 series of 15 Gy) in the first trial, and 55 (20, 20 and 15 Gy) in the second. The effect of the irradiated volume was investigated by comparing the local relapse rates in the group of patients treated by radiation fields encompassing the initial tumor volume to another group in which the initial target volume was not fully covered by radiation fields. The definition of these two groups was performed retrospectively by examination of radiological, fiberoptic bronchoscopy initial findings, technical radiation charts and check films. The local recurrence rate were 33 and 36% in each group (no significant difference). This finding could suggest that tumor shrinkage after chemotherapy might allow the use of "reduced" radiation volumes. However, the limited number of patients does not permit a definite conclusion. The effect of radiation dose was investigated by comparing the local control rates in the two consecutive trials which delivered 45 and 55 Gy, respectively. No difference in long-term local control was found: the addition of 10 Gy in the second trial only seemed to delay the appearance of local recurrences by 6 months. Twenty percent of patients died from a local relapse without evidence of distant metastases.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Alternating radiotherapy and chemotherapy schedules in limited small cell lung cancer: analysis of local chest recurrences. 185 72

Recently, the ganglioside FucGM1 (Fuc alpha 1-2Gal beta 1-3GalNAc beta 1-4[NeuAc alpha 2-3]-Gal beta 1-4Glc beta 1-1 Cer) was identified as a small cell lung cancer (SCLC) marker both in chemical and histochemical studies. In order to further determine whether the FucGM1 ganglioside is shed from the tumor site and consequently is present in the serum of SCLC patients, we produced a series of new monoclonal antibodies raised against FucGM1 and related glycolipids. Shedding of the FucGM1 ganglioside was studied both in vitro and in vivo using SCLC cell lines and nude mice xenografts of SCLC cells as model systems, and finally immunochemical analyses were performed on serum samples from patients with SCLC. High-performance thin-layer chromatography immunostaining demonstrated the presence of FucGM1 in conditioned culture media obtained from FucGM1-positive SCLC cell lines. Furthermore, tumor extracts of SCLC cell line xenografts in nude mice were positive for the FucGM1 marker, and more importantly the marker was also present in serum samples from these mice. Twenty serum samples were obtained from patients with histologically verified SCLC. Eight patients had localized disease, and the remaining patients had disseminated cancer involving metastases to other organ sites. Sera from 4 of these patients were clearly positive, and 2 additional cases were found to be weakly positive. The positive patient sera were all from patients with extensive disease. Sera from 12 patients with non-SCLC and 20 healthy individuals were all found to be negative. These results clearly establish the FucGM1 glycolipid as a potential serum marker of SCLC for which a sensitive immunoassay should be developed and tested using a larger series of serum samples.
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PMID:Immunochemical detection of a small cell lung cancer-associated ganglioside (FucGM1) antigen in serum. 185 63

The establishment of reliable preclinical test is essential for the reasonable clinical trial. As a methodology for the screening of new active anticancer agents, disease oriented strategy using human tumor cell lines has been proposed in USA. The important questions in DOS are to determine the representative cell lines of specific cancer and it is also extremely important to decide the numbers of cell lines used for the screening. CPT-11, topoisomerase I inhibitor, developed in my country has been demonstrated to be active against lung cancer cell lines compared with mice tumors such as S-180 and P-388. However, no compound is demonstrated to be clinically active so far by this methodology. The criteria for the application of clinical trial are obscure and each drug company decides empirically by themselves. We have proposed to use PEI (predictive efficacy index) for the prediction of antitumor activity of new compounds. The clinical effect of new platinum analogue well correlated with this value. We have conducted phase II trial of 5-FU + LV against NSCLC without no prior chemotherapy. No responder was observed in the trial. Augmentive effect of leucovorin on the cytotoxicity of 5-FU and FdUrd was examined in vitro against NSCLC and colon cancer cell lines. Leucovorin stimulated the cytotoxicity of both drugs only against colon cancer cell lines. We tried to predict the response rate of new platinum derivative based on the data of bioassay of patient's serum administrated with platinum compounds. The predicted response rates of 254-S were 57-67% and 16-27% against SCLC and NSCLC, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Preclinical trials from the standpoint of clinical trials]. 185 17

Inactivation of the retinoblastoma gene (RB gene) is associated with the development of several human malignancies including retinoblastomas, some osteo- and soft tissue sarcomas, small cell lung cancer, and possibly breast and bladder cancers. To our knowledge, this gene has not been evaluated in human germ-cell malignancies. In this study 67 primary testicular germ-cell tumors and 4 testicular non-germ-cell malignancies were examined to determine the prevalence and nature of RB gene alterations. Decreased expression of RB gene mRNA was found in all testicular germ-cell tumors (both seminomas and nonseminomas) examined. The RB protein could not be detected by immunohistochemical analysis in the undifferentiated cells of any germ-cell tumors whereas the differentiated malignant cells present in 14/15 teratocarcinomas expressed the protein. No gross alterations of the RB gene were found at DNA level in any of the examined specimens. This and the presence of the RB protein in the more differentiated tumor cells of teratocarcinomas suggest that changes in transcript levels rather than mutation(s) of the gene may be responsible for the absent or decreased RB expression in human germ-cell tumors. To date studies on the mechanism of RB regulation have demonstrated that it occurs at the protein level by phosphorylation of the p105 gene product. The findings presented here indicate that additional regulation might occur at the transcript level.
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PMID:Correlation between retinoblastoma gene expression and differentiation in human testicular tumors. 186 90


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