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)

Cancer metastasis is one of the major challenges in cancer research. Inhibitors of tumor metastasis are rapidly emerging as important new drug candidates for cancer therapy. Tumor metastasis formation occurs via a complex multistage process which involves a crucial step of tumor invasion through the basement membrane. Tumor cell invasion involves attachment of tumor cell to the basement membrane through laminin, degradation of the matrix by proteolytic enzymes from the tumor cell and cell migration through the basement membrane. New drugs aimed at the metabolism of tumor cell surface oligosaccharides and/or catabolism of glycoconjugates of extracellular matrix and basement membrane could inhibit tumor metastasis. In this article, current progress in the control of tumor metastasis by gem-diamine 1-N-iminosugars and related iminosugars (nojirimycin and d-glucaro-delta-lactam), which are potent and specific inhibitors of carbohydrate metabolism and catabolism, has been reviewed. gem-Diamine 1-N-iminosugars related to d-glucuronic acid and l-iduronic acid, nojirimycin and d-glucaro-delta-lactam suppress invasion of B16 melanoma variants and 3LL (lung carcinoma) cells through reconstituted basement membrane, and inhibit pulmonary metastasis of these tumor cells in mice and/or cKDH-8/11 (liver carcinoma) cells in rats. These results suggest that the metabolism of beta-d-glucuronide and alpha-l-iduronide of glycoconjugates and/or the processing of carbohydrates of tumor cell surface may participate in tumor metastasis. That these gem-diamine 1-N-iminosugars and related iminosugars are potent inhibitors of tumor metastasis holds promise of new drug candidates for cancer chemotherapy.
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PMID:gem-Diamine 1-N-iminosugars and related iminosugars, candidate of therapeutic agents for tumor metastasis. 1257 Aug 67

C.I. Direct Blue 15 is one of five chemicals being evaluated in 2-year carcinogenicity and toxicity studies as part of the NTP's Benzidine Dye Initiative. This Initiative was designed to evaluate representative benzidine congeners, benzidine congener-derived dyes, and benzidine-derived dyes. The dye, industrial grade C.I. Direct Blue 15, was chosen for study as a product to which workers are potentially exposed. Because of the high salt content, the dye was desalted prior to use. The purity was determined to be approximately 50%, with high-performance liquid chromatography indicating one major peak and approximately 35 impurities. Toxicology and carcinogenesis studies were conducted by administering the dye, C.I. Direct Blue 15, in drinking water to groups of F344/N rats of each sex for 14 days, 13 weeks, or 22 months. Planned as 24-month studies, the 22-month studies were terminated early because of rapidly declining animal survival, which was due primarily to neoplasia. These studies were performed only in rats because studies of benzidine congeners were being performed in mice at the National Center for Toxicological Research (NCTR). Genetic toxicology studies were conducted in Salmonella typhimurium and Chinese hamster ovary cells. 14-Day Studies: Rats were given C.I. Direct Blue 15 in drinking water at doses of 1,250, 2,500, 5,000, 10,000, or 30,000 ppm. All control and treated rats survived. Body weight gain in high-dose females was less than that in controls. Water consumption declined as the dose increased. Male and female rats receiving 30,000 ppm had slight degeneration and necrosis of individual hepatocytes in the liver, and females also had mild to moderate renal tubule degeneration and thymic lymphoid depletion. 13-Week Studies: C.I. Direct Blue 15 was administered in drinking water at doses of 0, 1,250, 2,500, 5,000, 10,000, or 30,000 ppm to male rats, and at doses of 0, 630, 1,250, 2,500, 5,000, or 10,000 ppm to female rats. Seven of 10 male rats receiving 30,000 ppm died; all rats in the other groups survived until the end of the studies. Mean final body weights of males receiving 10,000 or 30,000 ppm were 92% and 69% of those of controls, and mean final body weights of females receiving 5,000 or 10,000 ppm were 97% and 94% of those of controls. Tissues from treated animals were stained blue. Compound-related lesions were seen in the kidney and liver of male rats given 30,000 ppm and in the kidney of males and females given 10,000 ppm. The renal lesions included necrosis, degeneration, pigmentation and regeneration of the tubule epithelium, and tubule mineralization. Liver lesions included centrilobular hepatocellular degeneration, fatty metamorphosis, and individual cell necrosis with slight periportal hepatocellular hypertrophy. Lymphoid depletion in the thymus was also seen in the high-dose males. Based on the results of the 14-day and 13-week studies, the high dose chosen for the 22-month studies was 2,500 ppm. 22-Month Studies: At study initiation, 70 rats of each sex were given 0 or 2,500 ppm C.I. Direct Blue 15, 45 rats of each sex were given 630 ppm, and 75 rats of each sex were given 1,250 ppm. Interim evaluations were made at 9 and 15 months. The average amounts of compound consumed per day by the six dose groups after week 52 of the studies were estimated to be 45, 90, and 215 mg/kg for male rats and 50, 100, and 200 mg/kg for female rats. Survival and Body Weights: The studies were terminated at 22 months due to extensive mortality associated with chemical-related neoplasia. Survival of control, 630, 1,250, and 2,500 ppm males at 22 months was 37/50, 8/35, 11/65, and 2/50; survival of females was 40/50, 13/35, 22/65, and 4/50. At 22 months, the mean final body weights of the 630, 1,250, and 2,500 ppm groups were 95%, 91%, and 81% of those of the control for male rats and 91% of those of the control for all female dose groups. Histopathologic Effects in the 22-Month Studies: At the 9-month interim evaluations, one adenoma of the Zymbal's gland was seen in a high-dose male rat, and three carcinmbal's gland was seen in a high-dose male rat, and three carcinomas of the clitoral gland were seen in the high-dose females. At the 15-month interim evaluations, Zymbal's gland neoplasms were seen in low- and high-dose males and all treated female dose groups. Mid- and high-dose males and females also had preputial or clitoral gland neoplasms, and a few neoplasms were present in the skin, small and large intestine, liver, and oral cavity of treated animals at 15 months. At the end of the study, neoplasms related to chemical administration were found in the Zymbal's gland, skin, oral cavity, and the preputial or clitoral gland in both male and female rats. Neoplasms related to chemical administration were also seen at other sites including the small and large intestine, liver, uterus, and brain. The incidence of mononuclear cell leukemia was also increased in treated rats. Genetic Toxicology: C.I. Direct Blue 15 was not mutagenic in Salmonella typhimurium strains TA100, TA1535, TA1537, and TA98 when tested in a standard preincubation protocol with or without exogenous metabolic activation; however, when a specialized reductive metabolism protocol was used, C.I. Direct Blue demonstrated mutagenic activity in Salmonella strain TA1538. C.I. Direct Blue 15 did not induce sister chromatid exchanges or chromosomal aberrations in Chinese hamster ovary cells with or without S9 activation; reductive metabolism was not used in these cytogenetic tests. Conclusions: Under the conditions of these 22-month drinking water studies, there was clear evidence of carcinogenic activity of C.I. Direct Blue 15 (desalted industrial grade) in male F344/N rats, as indicated by benign and malignant neoplasms of the skin, Zymbal's gland, preputial gland, liver, oral cavity, and small and large intestine. Increased incidences of mononuclear cell leukemia and neoplasms of the brain may have been related to chemical administration. There was clear evidence of carcinogenic activity of C.I. Direct Blue 15 in female F344/N rats, as indicated by benign and malignant neoplasms of the skin, Zymbal's gland, clitoral gland, liver, oral cavity, small and large intestine, and uterus, and by mononuclear cell leukemia. Synonyms: Airedale Blue D, Aizen Direct Sky Blue 5BH, Amanil Sky Blue, Atlantic Sky Blue A, Atul Direct Sky Blue, Azine Sky Blue 5B, Belamine Sky Blue A, Benzanil Sky Blue, Benzo Sky Blue S, Benzo Sky Blue A-CF, Cartasol Blue 2GF, Chloramine Sky Blue A, Chloramine Sky Blue 4B, Chrome Leather Pure Blue, C.I. 24400, Cresotine Pure Blue, Diacotton Sky Blue 5B, Diamine Blue 6B, Diamine Sky Blue, Diaphtamine Pure Blue, Diazol Pure Blue 4B, 3,3'-[(3,3'-dimethoxy[1,1'-biphenyl]-4,4'-diyl)bis(azo)]bis[5-amino-4-hydroxy-2,-naphthalenedisulfonic acid] tetrasodium salt, Diphenyl Brilliant Blue, Diphenyl Sky Blue 6B, Direct Blue 10G, Direct Blue HH, Direct Pure Blue, Direct Pure Blue M, Direct Sky Blue (6CI), Direct Sky Blue A, Direct Sky Blue 5B, Enianil Pure Blue AN, Fenamin Sky Blue, Hispamin Sky Blue 3B, Kayafect Blue Y, Kayaku Direct Sky Blue 5B, Mitsui Direct Sky Blue 5B, Naphtamine Blue 10G, Niagara Blue 4B, Niagara Sky Blue, Nippon Direct Sky Blue, Nitto Direct Sky Blue 5B, Paper Blue S, Phenamine Sky Blue A, Pontamine Sky Blue 5BX, Shikiso Direct Sky Blue 5B, Sky Blue 4B, Sky Blue 5B, Tertrodirect Blue F, Vondacel Blue HH
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PMID:NTP Toxicology and Carcinogenesis Studies of C.I. Direct Blue 15 (CAS No. 2429-74-5) in F344 Rats (Drinking Water Studies). 1263 62

The level of disability and polypathology in hospitalized elderly is usually high. Multidimensional and functional assessment allows to identify risk factors for clinical and functional failure of patients. Many studies point out that identifying predictors of high-risk patients is a necessary step in accurate targeting. We evaluated 395 subjects (175 women, 202 men, mean age 77.9 year) during their hospitalization in our Geriatric ward. Baseline data included: demographics variables, medical diagnosis, functional evaluation, and laboratory values. After a 6-month follow up 80 (20.2%) subjects died. In our study, male gender, dependence at the Dependence Medical Index (DMI), low serum albumin (< 2.8 g/dl), impaired score at the Instrumental Activities of Daily Living scale (IADL), score lower than 13.7 at the acute physiology and chronic health evaluation (APACHE II) and neoplasm were independent predictors of 6-month post-hospitalization mortality. The high mortality rate of our sample could be a marker of considerable frailty among elderly patients. Our study shows that a poor functional status is a more reliable prognostic factor than type and number of admitting diagnosis. Clinical evaluation, improved with information about functional status, is a feasible and practical way of detecting risk of short term post-hospitalization mortality of elderly subjects.
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PMID:Post-hospitalization mortality in the elderly. 1284 2

Geriatric cancer patients present special challenges for clinicians. Few large series have been published in the last 20 years on the types of neoplasms that involve the central nervous system (CNS) in older individuals. To review types of neoplasms involving the central CNS that are currently being encountered by pathologists and neurosurgeons, we identified from our databases for the years 1992-2002, inclusive, patients 75 years or older who had symptomatic lesions requiring neurosurgical interventions. Retrospective characterization of tumors by immunohistochemistry, in situ hybridization, and fluorescence in situ hybridization was performed whenever possible and relevant to tumor type. Neurosurgical procedures (n=125) on 119 patients were identified; 90 patients were diagnosed as having neoplasms, with clot evacuation or infections being the most frequent non-neoplastic conditions necessitating surgery. Tumor types included glioblastomas (36 patients), meningiomas (16), pituitary adenomas (12), lymphomas or other hematological malignancies (8), anaplastic gliomas (5), metastases (6), head and neck malignancies with direct intracranial extension (3), and other miscellaneous tumor types (4). Compared with older literature series, we encountered a larger number of elderly patients with CNS lymphomas and fewer who came to surgery for CNS metastatic disease. In the "older old", glioblastomas are the most frequent symptomatic tumors necessitating surgical intervention. Glioblastomas in this aged cohort display the signature features of the small cell phenotype (62%), high cell cycle labeling indices (mean MIB-1-labeling index=25.1%), and either amplification of epidermal growth factor receptor or gain of chromosome 7 by fluorescence in situ hybridization (93% of assessable cases).
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PMID:Neoplasms involving the central nervous system in the older old. 1465 15

The purpose of this study was to address the question whether patients with bilateral breast cancer (BBC) have a worse prognosis in terms of recurrence and survival than patients with primarily unilateral breast cancer (UBC) following breast-conserving treatment (BCT). From 1983 to 2000, a total of 1760 BCT were registered in the Radiotherapy Department of the Medisch Spectrum Twente. We defined synchronous a BBC as cancer diagnosed in both breasts at the same time or within a period of 3 months of diagnosis of the first tumor. One thousand seven hundred and sixty BCT were performed on 1705 patients, 26 of whom presented with BBC. Of these 26 patients, 18 had BCT for both breasts. A higher proportion of patients with BBC showed more tubular carcinoma (P=0.029) and medially located tumors (P=0.076) than those with UBC did. The 5- and 10-year local recurrence rates (LRRs) were 4.5% and 9.1%, respectively, in BBC patients, as against 3.3% and 7.6% for UBC after BCT. The 5- and 10-year distant metastasis rates were 26.9% and 50.7%, respectively, for BBC as against 13.4% and 21.1% for UBC after BCT (P=0.065 and P=0.014, respectively). The 5- and 10-year disease-specific survival (DSS) rates for the 1705 patients were 82.1% and 41%, respectively, after BBC, and 91.4% and 84% after UBC (P=0.086 and P=0.0045, respectively). Patients with BBC have a higher rate of distant metastasis and a worse DSS than those with UBC. As the LRR is similar for BBC and UBC, BCT is not contraindicated in BBC. The incidence of BBC is low, at 1.5% which makes it difficult to reach any more definitive conclusions on outcome and treatment.
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PMID:Synchronous, bilateral breast cancer: prognostic value and incidence. 1517 34

A renal mass with not typical instrumental characteristic in patient in follow-up for ovarian neoplasia sets to the surgeon serious doubts about proper surgical strategy. Achieve of the conservative renal surgery assisted by the intraoperative use of the radiofrequency energy has allowed to preserve the renal function and the diagnosis of unknown angiomyolipoma.
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PMID:[Atypical presentation of angiomiolypoma in a patient with peritoneal metastases from ovarian cancer: a case report]. 1511 57

Patients who are > or =65 years of age are the fastest growing segment of the U.S. population. These patients with already existing physiologic decline and comorbidities, when diagnosed with cancer, provide considerable challenges in management issues. Along with therapy for the tumor the practicing oncologist must also keep in mind the various symptoms, like fatigue, pain, and depression, that may occur due to the tumor itself or due to therapy. The prevalence of fatigue is greater than 50-70% in advanced cancer. The tools to measure fatigue are all subjective in nature and no one tool has been tested in the elderly cancer patient. Treatment of fatigue in the elderly may involve education, antidepressants, treatment of anemia, exercise, and use of psychostimulants. Pain is present is 80% of elderly patients with advanced cancer. Pain should be assessed in a systematic way and it has been shown that the Visual Descriptor Scale is the tool most preferred by the elderly. Several guidelines for management of pain exist and options include acetaminophen, nonsteroidal anti-inflammatory drugs, opioids, adjuvant analgesics, and education of patients and caregivers. Depression is also a prevalent symptom arising from a variety of causes. There are many validated tools to measure depression in the elderly like the Geriatric Depression Scale. Treatment includes use of education, selective serotonin reuptake inhibitors, psychotherapy, and electroconvulsive therapy. There exists an interplay of many of these symptoms and quite often they can occur simultaneously in the elderly cancer patient. Future research is needed to expand our base of knowledge on the occurrence and management of each of these symptoms and to better understand how aging systems interact with these phenomena to produce unique situations in older adults.
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PMID:Symptom management in the elderly cancer patient: fatigue, pain, and depression. 1526 59

Four anthraquinones isolated for the first time from the aerial parts of Rumex acetosa (Polygonaceae), a Korean and a Japanese medicinal plant, and two synthetic derivatives were examined for their cytotoxicities against five cultured human tumor cell lines, i.e. A549 (non-small cell lung), SK-OV-3 (ovary), SK-MEL-2 (melanoma), XF498 (central nerve system) and HCY15 (colon), using the Sulfrhodamine-B method in vitro and antimutagenic activities by Ames test with Salmonella typhimurium TA98 and TA100 and SOS chromotest with E. coli PQ37. Among the tested compounds, emodin strongly inhibited the proliferation of each examined tumor cell line with IC50 values ranged from 2.94 to 3.64 microg/ml and showed potent antimutagenic activities with 71.5% and 53.3% at the concentration of 0.1 mg/plate against the mutagens, NPD and sodium azide, respectively. Its antigenotoxic activity was also very effective at the final concentration of 10 microg/reaction tube against the mutagens, MNNG and NQO by SOS chromotest, reducing the induction factors by 19.6% and 43.5%, respectively. The structure-activity correlation study suggests that an additional OH group at C-6 position in the anthraquinone nucleus may play an important role for their cytotoxicities and an introduction of OH- or OCH3 group at C-6 position is necessary for their antimutagenicities.
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PMID:Antimutagenicity and cytotoxicity of the constituents from the aerial parts of Rumex acetosa. 1627 11

Remarkably, although 60% of new cancer cases and over 70% of cancer deaths occur in patients aged 65 years and older in Europe, standard treatment strategies have been mostly validated in younger adults. This demographic trend has led to the emergence of a new medical discipline, geriatric oncology and the development worldwide of geriatric oncology programs for the individualized management of elderly cancer patients. Elderly cancer patients represent an increasing share of the population and strategies for treating cancer must evolve to face this ineluctable reality. Treatment should take into account the highly heterogeneous physiological age of the elderly, their individual life expectancy, functional reserves, social support and preferences. French geriatric oncology programs have been mostly based on the interdependence of geriatricians, oncologists and auxiliary nursing people. This approach represent the best way to offer patients optimal management; oncologists and geriatricians collaborate to assess both global health status by means of Comprehensive Geriatric Assessment (CGA) and tumor stage by means of Comprehensive Tumor Assessment (CTA) and to initiate individualized care plans, involving comprehensive management and follow-up of all identified problems. This paper focuses on progress observed in the field of geriatric oncology both in France and worldwide.
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PMID:[What's new in geriatric oncology?]. 1645 14

The Informational Spectrum Method (ISM) is the tool for the in silico analysis of proteins which interprets protein sequence linear information using signal analyses methods. In this paper the ISM was employed to characterize the products of genetic variants of tumor suppressor gene p53 and its natural binding regulator protein Mdm2. Based on this we propose the criterion for identification of missense mutations that have impact on the p53-Mdm2 feedback loop. The efficiency of the proposed criterion was confirmed by the ISM analyses of p53 mutants reported in: (i) healthy individuals, (ii) germline mutations database and (iii) somatic mutations database.
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PMID:In silico criterion for prediction of effects of p53 gene missense mutations on p53-Mdm2 feedback loop. 1707 27


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