Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242379 (lung cancer)
 71,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The L-MYC restriction fragment-length polymorphism (RFLP) revealed by EcoR1 has been suggested to be of prognostic significance in lung, breast, and kidney cancer. The presence of the smaller allele, in either the homozygotic (S-S) or heterozygotic form (L-S), is felt to convey a worse prognosis than the homozygotic form for the larger allele (L-L). The significance of this relationship in lung cancer has been questioned recently. The objective of the present study was to test the prognostic significance of the L-MYC allelotype in a group of renal cell carcinoma (RCC) patients. Tumor and normal tissue were obtained from 59 patients who underwent radical nephrectomy for RCC between 1986 and 1990. EcoR1 restriction digests were performed on isolated DNA and hybridized with the L-MYC probe. Allelotypes were correlated with pathologic parameters and clinical outcome using the chi 2 test. The L-MYC alleolotype (L-L versus L-S and S-S) did not correlate with any pathologic parameter or likelihood of disease recurrence and does not offer any clinical utility in patients with RCC.
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PMID:L-MYC allelotype in renal cell carcinoma. 863 Sep 82

The incidence of cancers of the kidney and urinary bladder in Inuit 1969-1988 was studied as part of an international collaboration combining results from cancer registries for Circumpolar Inuit residing in Alaska, Canada and Greenland. Significant high risk of renal cancer was found in Inuit women (SIRs 1.4-2.1) and the age-standardized incidence rate among women was one of the highest on record world-wide. Cancer of the urinary bladder, as opposed to renal cancer, was an uncommon malignancy in both sexes with SIRs of 0.2 to 0.4. No consistent time trend was observed for either renal or bladder cancer in contrast to high and sharply increasing lung cancer rates during the same period. Such results are more likely caused by different latency periods for renal and bladder cancer than for lung cancer following tobacco exposure, possibly combined with the absence of certain occupational exposures relevant to bladder cancer.
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PMID:Kidney and bladder cancer in Inuit 1969-1988. 881 67

Until the introduction of self-service around 1970, service station workers in the Nordic countries were exposed to gasoline vapors. Based on measurements reported in the literature, the 8-hour time-weighted average benzene exposure was estimated to be in the range of 0.5-1 mg/m3. We studied the cancer incidence in a cohort of 19,000 service station workers from Denmark, Norway, Sweden, and Finland. They were identified from the 1970 censuses and followed through 20 years, where 1,300 incident cancers were observed. National incidence rates were used for comparison. The incidence was not increased for leukemia (observed = 28, standardized incidence ratio (SIR) = 0.9, 95% confidence interval (CI) 0.6-1.3) not for acute myeloid leukemia (observed = 13, SIR = 1.3, 95% CI 0.7-2.1). The incidence was slightly elevated for kidney cancer observed = 57, SIR = 1.3, 95% CI 1.0-1.7) and for pharyngeal, laryngeal, and lung cancer. A 3.5-fold risk of nasal cancer was found (observed = 12, SIR = 3.5, 95% CI 1.8-6.1). This cohort exposed to gasoline vapors with benzene levels estimated to be 0.5-1 mg/m3 showed no excess risk of leukemia or acute myeloid leukemia, a 30% elevated risk of kidney cancer, and a previously unnoticed risk of nasal cancer.
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PMID:Risk of cancer and exposure to gasoline vapors. 904 19

The antitumor effects of "half-mustard type" phenothiazines were studied on 57 different tumor cell lines, including leukemias, non-small lung cancer, colon, central nervous system, ovarian, renal, breast, and prostate cancer, as well as melanoma cell cultures. Alkyl-urea derivatives of phenothiazines displayed in vitro antitumor activity. The phenothiazine phthalimido derivatives (1-6) were not active on the majority of cancer cell cultures. In contrast, propylureas (9, 11) were active against some leukemia cell types. Only two compounds with the butylene [(CH2)4] linker (10, 12) were active against non-small lung cancer cells. Compounds containing the propylene linker were less effective. On colon cancer lines, tumor cells from the central nervous system and on melanoma cells the same compounds were effective, however, having substituents at the 2-position of phenothiazine seems to be important. Surprisingly, the majority of ovarian cancer cell lines (except one type, IGROVI) and five of eight renal cancer lines were not sensitive to these phenothiazine derivatives. The two butylene linked phenothiazine ureas (10, 12) had moderate antiproliferative action on two renal cancer cell lines. The prostate cancer and some breast cancer cell lines were not sensitive. Nevertheless some breast cancer cell lines were apparently sensitive to CF3-substituted phenothiazine alkylureas. On the basis of these experiments one may postulate that in the case of insensitive cells an mdr-gene encoded multidrug resistance efflux pump is responsible for the resistance. The selectivity or organ cell specificity of the effective phenothiazines will be targeted for improvement in further studies, in order to avoid the general cytotoxic effects of "half mustard type" phenothiazines.
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PMID:The primary in vitro antitumor screening of "half-mustard type" phenothiazines. 941 80

The tumor-specific increased minimal requirement for methionine has been shown to be a highly promising therapeutic target. To attack this target we have previously cloned the methioninase gene from Pseudomonas putida and produced recombinant methioninase (rMETase). A pilot Phase I clinical trial has been carried out to determine rMETase toxicity, rMETase pharmacokinetics, and serum MET-depletion in cancer patients. Patients with advanced breast cancer, lung cancer, renal cancer and lymphoma were given a single rMETase treatment at doses ranging from 5,000 to 20,000 units by i.v. infusion over 6-24 hours. No clinical toxicity was observed in any patient after rMETase treatment. rMETase levels reached 0.1 to 0.4 units per ml of serum in the patients which correspond to therapeutic levels in vitro. The lowest serum methionine levels in rMETase-treated patients were 0.1% of the pre-treatment levels corresponding to approximately 0.1 microM, which also correlates to therapeutic levels in vitro. The results of the rMETase pilot Phase I clinical trial therefore indicate that i.v. infusion of rMETase is safe and effectively depletes its biochemical target of serum methionine suggesting potential efficacy in future clinical trials.
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PMID:Recombinant methioninase infusion reduces the biochemical endpoint of serum methionine with minimal toxicity in high-stage cancer patients. 942 92

Recombinant methioninase (rMETase) is a homotetrameric pyridoxal 5'-phosphate enzyme of 172-kda molecular mass derived from Pseudomonas putida and cloned in Escherichia coli. rMETase has been found previously to be an effective, anti-tumor agent in vitro and in vivo. The enzyme targets the elevated minimal methionine requirement seen in all tumor types. In order to prevent immunological reactions which might be produced by multiple dosing of rMETase and to prolong the serum half-life of rMETase, the N-hydroxysuccinimidyl ester of methoxypolyethylene glycol propionic acid (M-SPA-PEG 5000) has been coupled to rMETase. Molar ratios of M-SPA-PEG-5000 (PEG) to rMETase from 10 to 40 were used for PEGylation of rMETase. PEGylation reactions were run at 20 degrees C for 30 to 60 min in reaction buffer (20 mM sodium phosphate buffer, pH 8.3). The PEGylated molecules (PEG-rMETase) were purified from unreacted PEG with Amicon 30 K centriprep concentrators or by Sephacryl S-300 HR gel-filtration chromatography. Unreacted rMETase was removed by DEAE Sepharose FF anion-exchange chromatography. The resulting PEG-rMETase subunit, from a PEG/rMETase ratio of 30/1 in the synthetic reaction, had a molecular mass of approximately 53 kda determined by matrix-assisted laser desorption/ionization mass spectrometry, indicating the conjugation of two PEG molecules per subunit of rMETase and eight per tetramer. PEG-rMETase molecules obtained from reacting ratios of PEG /rMETase of 30/1 had enzyme activities of 70% of unmodified rMETase. PEGylation of rMETase increased the serum half-life of the enzyme in rats to approximately 160 min compared to 80 min for unmodified rMETase. PEG-rMETase could deplete serum methionine levels to less than 0.1 microM for approximately 8 h compared to 2 h for rMETase in rats. Efficacy studies of PEG-rMETase on human lung cancer and kidney cancer cells in vitro demonstrated a 50% inhibitory concentration (IC50) of 0.04 and 0.06 units/ml, respectively. These IC50 values were almost identical to unmodified rMETase, thus indicating maintenance of antitumor efficacy in the PEGylated enzyme. PEG-rMETase had an IC50 for normal lung and kidney cells of 0.8 and 1.5 units/ml, respectively, similar to rMETase. The efficacy data indicated that PEG-rMETase maintained the high level tumor selectivity of rMETase. PEG-rMETase injected intravenously in mice demonstrated a tumor/blood retention ratio of approximately 1/6 compared to 1/10 of unmodified enzyme, indicating that PEG-rMETase distributes to the tumor at least as effectively as rMETase.
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PMID:Polyethylene glycol conjugation of recombinant methioninase for cancer therapy. 947 56

Some new phenothiazines have been synthesized on the basis of previous studies. The anticancer activity of "half-mustard type" phenothiazines was investigated on sixty different cancer cell lines in vitro. The percentage of growth (PG), 50% inhibition of growth (GI50), the tumor growth inhibition (TGI) and the concentration required for 50% lethality of cells (IC50) were examined and calculated in the presence of various (from 10(-4) to 10(-8) M) concentrations of phenothiazine alkylurea derivatives. The following cell lines were involved in the study: 6 leukemia, 9 non-small-cell lung cancer, 7 colon cancer, 6 central nervous system cancer, 8 melanoma, 6 ovarian cancer, 8 renal cancer, 2 prostate and 8 breast cancer cell lines. The antileukemic activity of four chloroethyl-substituted phenothiazine-alkylureas was shown by considerable growth inhibition, in the 10(-5) M range, of the six different leukemia cell lines. The 50% inhibition of growth was nearly the same for the four compounds on all cell lines. Tumor growth inhibition (TGI) and IC50 value to cells varied from -4.0 to -4.66. The two derivatives with the butylene bridge were more effective than propylene linked compounds against the CCRP-CEM, HL60 (TB), K-562 and MOLT-4 cell lines. However, the anti-leukemic activity of the derivatives was nearly the same for RPMT 8226 and SR cell lines. The substituent at the 2- position of phenothiazine ring and the length of the linker between the side chain nitrogen and the phenothiazine ring system are apparently important for antileukemic activity. Four of the 9 non-small-cell lung cancer cell lines were sensitive, while the other 5 cell lines were not. The compounds had a slight growth inhibitory effect on colon cell carcinoma and melanoma cells in which case the butylene linker seemed to be more effective than the propylene linker. At the same time, all of the compounds were weak or mostly inactive on cancer cells from the central nervous system. One ovarian cancer line of the 6, the IGROVI was sensitive to butylurea phenothiazines, however, the other five were not sensitive at all. The difference in the sensitivity of various renal cell carcinomas was significant: 5 lines were not sensitive, three of them (786-0, RXF-393 and TK-10) were sensitive to only butylene-substituted phenothiazine-ureas, propylene substitution resulted in ineffective compounds. The compounds were not able to inhibit the 2 prostate and 4 breast cancer cell lines, even at 10(-4) M. It was interesting that propylene-linked ureas were more effective than butylene-linked derivatives on MCF-7, but butylene-linked derivatives were more effective than propylene-linked compounds on MDA MB-231 and MDA-N. In addition, MDA MB 435 was more sensitive to the trifluoromethyl derivatives than the compounds without this substituent. Since the phthalimido-alkyl phenothiazines were not active at the first level of prescreen, these compounds were omitted from this study. The drug sensitivity of some cancer cell lines was not uniform for the different groups, therefore we postulate that the resistance can be related to some kind of (existing) drug-efflux mechanism. Apparently, the tumor specificity of phenothiazine alkylureas is more related to the leukemia specificity of alkylureas than to any CNS or lung specificity of phenothiazines.
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PMID:The primary in vitro anticancer activity of "half-mustard type" phenothiazines in NCI's revised anticancer screening paradigm. 956

Because of the high density of industries along the Lower Mississippi River, there is a concern about adverse impact on health, including cancer, among residents in these parishes. This study provides an update of cancer incidence in the Industrial Corridor for the period 1989-93. Age-adjusted cancer incidence rates were calculated for the seven-parish study area from Baton Rouge down to, but not including, New Orleans. Rates were also computed for the entire state of Louisiana and for the combined Surveillance, Epidemiology and End Results (SEER) program. Cancer incidence rates for the Industrial Corridor are either similar to, or lower than, the combined SEER rates for most of the common cancers as well as for rare tumors. The only two exceptions are lung cancer in white males and kidney cancer in white females that are significantly elevated when compared to the SEER averages. Significantly lower rates are found among white males for cancers of kidney, brain, and nervous system, and melanoma; among black males, cancers of all sites combined, oral cavity, stomach, rectum, and prostate, Hodgkin's disease, and non-Hodgkin's lymphoma; among white females, cancers of all sites combined, cervix, uterine corpus, ovary, bladder, and melanoma; and among black females, cancers of all sites combined, oral cavity, lung, breast, ovary, and melanoma. The persistent excess of lung cancer has led to the development of a multi-agency project to evaluate the impact of potential environmental exposures, genetic susceptibility, and their interactions on lung cancer risk. The findings also confirm the urgent need to include and strengthen tobacco prevention and cessation programs in our cancer control activities.
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PMID:Cancer incidence in the industrial corridor: an update. 961 70

Cancers seen and recorded between 1983 and 1995 in the Hospital Tumor Registry at the American University of Beirut Medical Center (AUBMC), one of the largest primary and tertiary care hospitals in Lebanon, were retrospectively reviewed and analyzed. There was a total of 10,220 cases, excluding 916 skin cancers other than skin melanoma, averaging 786 cases per year. There were 5086 cancer cases in males with the five most common cancers being: lung cancer (915 cases: 17.9%) followed by bladder cancer (503 cases: 9.8%), larynx (438 cases: 8.6%), lymphoma (393 cases: 7.7%) and leukemia (336 cases: 6.6%). As for female cancer cases, a total of 5134 cases were observed with the five most common cancers being: breast cancer (1821 cases), followed by cervical cancer (535 cases), colo-rectal cancer (256 cases: 4.9%), lymphoma (232 cases: 4.5%), and brain cancer (213 cases: 4.1%). The average age for all cancer cases was 50.5 years with a standard deviation (SD) of 18.8 years. The average age of females (48.8 yrs; SD 17.4) was relatively lower than that of males (52.2 yrs; SD 19.9) and the difference was statistically significant. 40.6% of the patients were under the age of 50 years. 49% of breast cancer patients were below 50 years of age. In children less than 15 years of age, there were 555 cases, with leukemia being the commonest (185 cases: 33.3% of childhood cases) followed by brain cancer (112 cases: 20.1%), lymphoma (63 cases: 11.3%), bone cancer (41 cases: 7.3%), soft tissue sarcoma (35 cases: 6.3%) and kidney cancer (28 cases: 5.0%). Lung cancer in males and breast cancer in females are the most common cancers in Lebanon. These cancers are amenable to prevention (cigarette cessation and anti-smoking campaigns for lung cancer) and early detection (screening, regular breast examination and mammography for breast cancer). Our paper emphasizes the importance of addressing those and other issues including bladder cancer and age at diagnosis of breast cancer. It also presents important epidemiological and historical reference data on cancer in Lebanon during the civil war and immediately after it.
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PMID:Cancer in Lebanon: analysis of 10,220 cases from the American University of Beirut Medical Center. 979 15

The focus of this article is to examine how the choice of comparison group affects the identification and interpretation of cause-specific health risks in occupational cohorts when different external control populations are used. The mortality experience of approximately 31,000 high nickel alloys workers is compared with the total US population and to local populations in geographic proximity to the plants. Generally, the patterns of relative risks derived for the total cohort and various subgroups are similar across the different comparison populations. Estimated elevated risks are usually lower when cohort mortality is compared with that of local populations. An overall significant 13% risk for lung cancer is noted when compared with that of the total US population. However, no significant excess is identified when local populations are used. Subset analysis identified significant excesses of colon cancer among nonwhite males (50%-150%) and kidney cancer among white male workers employed in melting (approximately 100%), irrespective of the comparison population.
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PMID:Using alternative comparison populations to assess occupation-related mortality risk. Results for the high nickel alloys workers cohort. 980 Jan 77


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