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)

The effect of combinations of the anthracyclines aclarubicin and daunorubicin was investigated in a clonogenic assay using the human small cell lung cancer cell line OC-NYH and a multidrug-resistant (MDR) murine subline of Ehrlich ascites tumor (EHR2/DNR+). It was found that the cytotoxicity of daunorubicin in OC-NYH cells was antagonized by simultaneous exposure to nontoxic concentrations of aclarubicin. Coordinately, aclarubicin inhibited the formation of daunorubicin-induced protein-concealed DNA single-strand breaks and DNA-protein cross-links in OC-NYH cells when assayed by the alkaline elution technique. Aclarubicin had no influence on the accumulation of daunorubicin in these cells. In contrast, the accumulation of daunorubicin in EHR2/DNR+ cells was enhanced by more than 300% when the cells were simultaneously incubated with the MDR modulator verapamil, aclarubicin, or the two agents combined. Yet the cytotoxicity of daunorubicin was potentiated significantly only by verapamil. The increased cytotoxicity of daunorubicin in the presence of verapamil was completely antagonized when aclarubicin was used together with the MDR modulator. Finally, the effect of daunorubicin on the DNA cleavage activity of purified topoisomerase II in the presence and absence of aclarubicin was examined. It was found that daunorubicin stimulated DNA cleavage by topoisomerase II at specific DNA sites. The addition of aclarubicin completely inhibited the daunorubicin-induced stimulation of DNA cleavage. Taken together, these data indicate that aclarubicin-mediated inhibition of daunorubicin-induced cytotoxicity is due mainly to a drug interaction with the nuclear enzyme topoisomerase II. This antagonism at the nuclear level explains why aclarubicin is a poor modulator of daunorubicin resistance even though aclarubicin is able to increase the intracellular accumulation of daunorubicin in a MDR cell line.
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PMID:Antagonistic effect of aclarubicin on daunorubicin-induced cytotoxicity in human small cell lung cancer cells: relationship to DNA integrity and topoisomerase II. 165 44

Two human small cell lung cancer tumor lines, maintained as solid tumor xenografts on nude mice and as in vitro cell cultures, were studied by in vivo 31P magnetic resonance spectroscopy and by biochemical analysis of extracts of solid tumors and cell cultures. The tumor lines CPH SCCL 54A and CPH SCCL 54B are subpopulations from the same tumor. In solid tumors (n = 125), the ATP/Pi ratio was greater in 54A than in 54B. This was due to a higher ATP level in 54A, whereas there was no difference in Pi, ADP, and AMP. A decrease in ATP/Pi during growth was caused by a decline in ATP, whereas Pi remained unchanged. Small amounts of phosphocreatine were found in the xenografts and in tumor extracts, but not in the cell extracts; correspondingly, there was a low creatine kinase activity in solid tumors and no activity in the cell cultures. Thus, the phosphocreatine content of the solid tumors originated from the stroma. A difference in ATP content between 54A and 54B was also found in cell cultures; hence, the metabolic difference is an intrinsic quality of the malignant cells and is not caused by the host system.
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PMID:Different energy metabolism in two human small cell lung cancer subpopulations examined by 31P magnetic resonance spectroscopy and biochemical analysis in vivo and in vitro. 165 47

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

Based upon the pertinent literature, the paraneoplastic syndrome of inappropriate antidiuretic hormone secretion (SIADH) in patients with small cell lung cancer is reviewed. Small cell lung cancer is a distinct tumor with neuroendocrine features capable of producing peptide hormones amongst which the antidiuretic hormone (ADH, arginine vasopressin) is one of the most frequent. Paraneoplastic SIADH may result from ectopic ADH production or from other tumor-related mechanisms leading to increased pituitary ADH secretion. The overt SIADH is characterized by neurological and psychiatric symptoms attributable to cerebral edema. Pooled published data suggest that the average incidence of clinically manifest SIADH in patients with newly diagnosed small cell lung cancer is 4%. Cases without clinical symptoms, detectable by laboratory tests only, are more frequent: hyponatremia, serum hypoosmolality and urine hyperosmolality are present in 14%, and an inappropriately elevated level of immunoreactive ADH in 38% of all patients respectively. Successful treatment of the underlying tumor, accompanied by a restricted fluid intake in severe cases, will usually result in prompt disappearance of the paraneoplastic SIADH. During and after the tumor treatment, plasma ADH may be useful as a tumor marker.
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PMID:[Syndrome of inappropriate ADH secretion (SIADH) in small-cell bronchus carcinoma]. 165 20

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

A 63-year-old man with pulmonary sarcoidosis, diagnosed by mediastinal lymph node biopsy in 1977, was admitted in Feb. 1987 because of shortness of breath and cough. Chest X-ray showed bilateral hilar lymphadenopathy and a tumor shadow in the right lung field. Histological examination of specimens biopsied from the right lung revealed small cell carcinoma (S.C.C.). Bronchoalveolar lavage was performed to evaluate the disease activity of sarcoidosis, and the total number of cells and T-lymphocytes; the ratio of CD4+ cells to CD8+ cells was not increased. He was treated with combination chemotherapy, however, he died of respiratory failure after 7 months. An autopsy was performed, and the lesions were examined histologically. The sarcoid lesion in a lymph node obtained at autopsy was not active, in contrast to that obtained by mediastinal lymph node biopsy. Lung cancer and sarcoidosis are both common diseases, but their coexistence in the same patient is not common, and autopsied cases are rare. In this case, an autopsy was performed, and BAL had been performed prior to his death. The relationship between the BAL findings and the histology of sarcoidosis was examined. Based on the results of autopsy and BAL, the sarcoidosis was inactive prior to death, but had been histologically active 10 years previously. Therefore, this is a very interesting case, since we can examine the relationship between the two diseases, and the progression of each disease. This case also provides an interesting example of differentiation of sarcoidosis from S.C.C. Metastatic invasion of the hilar lymph nodes without bronchial stenosis and changes secondary to stenosis may often occur in patients with small cell lung cancer. Such metastatic invasion closely resembles the bilateral hilar lymphadenopathy of sarcoidosis; therefore, in some cases, it may be extremely difficult to differentiate the two diseases.
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PMID:[A case of small cell lung cancer associated with pulmonary sarcoidosis]. 166 44

In this study, we show that bispecific hetero-F(ab')2 enhances cytolytic activity in human lymphokine activated killer (LAK) cells derived from peripheral blood mononuclear cells against human small cell lung cancer (SCLC) cell lines. We used two types of bispecific F(ab')2 (anti-CD3-LU246mAb, anti-CD16-LU246mAb) which play different roles in the enhancement of cytolytic activity in LAK cells against the human SCLC cell lines N231, H69 and Lu135. Anti-CD3 Fab' or anti-CD16 Fab' were coupled with LU246 Fab' that recognized the antigen on human SCLC cells for reproducing bispecific F(ab')2. Anti-CD16 (3G8) Fab' conjugated with LU246 Fab' targeted NK-LAK cells to SCLC cells to mediate cytolysis, but NK-LAK cells induced by LGL-enriched fraction did not display enhanced cytotoxicity even when bispecific antibody was used in 51Cr release assay. Anti-CD3 (OKT3) Fab' conjugated with LU246 Fab' cross-linked T-LAK cells to SCLC cells activated T-LAK cells through the CD3 complex, and enhanced the cytolytic activity of T-LAK cells against SCLC lines. Although OKT3-LU246 F(ab')2 was not so potent in enhancing cytolytic activity in 51Cr release assay, it played a greater role in enhancing the inhibitory effect on tumor growth than 3G8-LU246 F(ab')2 in human tumor clonogenic assay and in vivo tumor neutralization assay. In addition, the enhancement of target cell lysis by bispecific antibodies was generally more potent than antibody dependent cellular cytotoxicity (ADCC) using LU246 monoclonal antibody.
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PMID:[The enhancement of cytolytic activity in lymphokine activated killer cells using bispecific F(ab')2]. 166 20

A total of 14 patients with locally advanced and unresectable head and neck (SCCHN) or non small cell lung cancer were treated with a definitive course of radiation therapy with conventional fractionation and 30 mg/m2 carboplatin (CBDCA) given daily as an i.v. infusion during the 1st, 3rd, 5th and 7th weeks of the combined treatment. The planned tumor dose of at least 7000 cGy was reached in all SCCHN patients except 1 (6600 cGy). The 2 NSCLC patients received 6320 and 5980 cGy, respectively. The planned total CBDCA-dose of 600 mg/m2 was administered in all patients. No treatment delays were required in 10 patients. Interruptions for severe mucositis or myelosuppression occurred in 4 patients (28.6%), but in no case did the delay exceed 1 week. Complete response was obtained in 8 patients (57.1%); 7 of the 12 with SCCHN and 1 of the 2 with NSCLC. The other 6 patients achieved a partial response. Granulocytopenia of WHO grade 3 occurred in 1 patient; apart from vomiting and mucositis, toxicities above grade 2 were not observed.
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PMID:Daily low-dose carboplatin and standard radiotherapy in unresectable head and neck and lung cancers: a pilot study. 166 54

The clinical manifestations, pathology and surgical treatment of 10 cases of primary esophageal small cell carcinoma were presented with a detailed review of literature. The 10 cases accounted for 0.7% of all esophageal carcinomas treated surgically in the same period. The major symptom was dysphagia. 50% were of exophytic type grossly (fungating or intraluminal). The microscopic findings were not different from those of small cell lung cancer. All of these 10 cases had their cancer radically resected. The one and two year survival rates were 50% and 25%, respectively. The median survival time was 15.2 months. Case 2 has been living tumor-free for 48 months. The results of surgical treatment of this rare type esophageal carcinoma was poor as compared to that of squamous cell carcinoma of the esophagus.
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PMID:[Primary esophageal small cell carcinoma--a report of 10 cases and review of literature]. 166 17

1. Elevated levels of fibrinogen were observed in 100% of untreated patients with SCCL. The elevated fibrinogen tended to normalize with complete remission in response to combination chemotherapy. 2. FDPs were increased in 33% of patients in the limited disease group and in 37% in the extensive disease group. Elevated levels of D-dimers were seen in 26% in the limited disease group and in 50% in the extensive disease group. Levels of FDPs did not parallel levels of D-dimers. Some cases of very advanced disease showed increases in both FDPs and D-dimers. 3. When FDPs were within normal limits, D-dimers tended to be elevated. 4. Levels of plasminogen, alpha 2-antiplasmin, and plasmin were and remained within normal limits throughout the course of treatment, while concentrations of FDPs and D-dimers increased. 5. Plasminogen, alpha 2-antiplasmin, plasmin, FDPs and D-dimers did not show any trend. 6. Peripheral blood measurements did not reflect the crucial role of plasmin in modulating blood fibrinolysis and the metastatic cascade. 7. Evidence of the action of the fibrinolytic system at tumor sites failed to correlate with results of laboratory tests.
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PMID:Fibrinolytic profiles in patients with small cell carcinoma of the lung. 166 89


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