Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ototoxicity of cis-diammine glycolato platinum, 254-S, was evaluated from the results obtained in phase II studies for head & neck cancer, lung cancer, breast cancer, gastrointestinal cancer, urogenital cancer and gynecological cancer at 114 institutions, and in randomized comparative study of 254-S plus vindesine vs. cisplatin plus vindesine for advanced non-small cell lung cancer conducted at 41 institutions. In these studies, 254-S was administered at doses ranging from 80 to 100 mg/m2, repeated at least 2 times at 4-week intervals. Impaired hearing was examined in a hearing audiometry test before and after 254-S administration. The incidence of impaired hearing was 25.8% (16/62) in the 254-S phase II studies. The incidences in the randomized comparative study were 17.6% (3/17) for the 254-S/vindesine group and 20.0% (3/15) for the cisplatin/vindesine group. From these results, the ototoxicity of 254-S was thought to be similar to that of cisplatin in incidence and type.
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PMID:[Ototoxicity of cis-diammine glycolato platinum, 254-S]. 150 88

Methionine metabolism is altered in cancer, and methionine labeled with 11C has been successfully used for imaging of brain, lung, and breast cancer and lymphoma. Uptake of L-[methyl-11C]methionine (11C-methionine) in head and neck cancer of 23 patients was studied with PET. Accumulation of 11C-methionine in the tumors was assessed by two different methods: the influx constant, Ki, and the standardized uptake value (SUV). All 23 cancers accumulated 11C-methionine. The mean Ki was 0.147 +/- 0.070 min-1 and the mean SUV 8.5 +/- 3.5. There was a strong correlation between the two measures of tumor uptake (r = 0.92, p less than 0.0001). There was no correlation between the uptake of 11C-methionine and the histological grade of cancer. Head and neck cancer can thus be effectively imaged with 11C-methionine. Carbon-11-methionine PET imaging may be useful in delineating tumors for therapy planning.
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PMID:Carbon-11-methionine and PET is an effective method to image head and neck cancer. 156 77

This update of the experience at the University of California at Irvine with laser photoradiation therapy (PRT) encompasses the period between May 1981 and June 1983. The results of treatment of 77 patients are reported (head and neck, 39; breast, 33; and lung 5). Head and neck cancer patients received treatment to 114 sites with a complete response (CR) in 28, partial response (PR) in 42, stable disease (SD) in three, and no response (NR) in 34, and an undetermined response in seven. Breast cancer patients were treated in 395 sites with CR in 222, PR in 74, SD in one, NR in 92, and undetermined response in six. The lung cancer patients in this series responded poorly, if at all. In addition to the above patient trials, we have investigated the interaction of laser hematoporphyrin derivative (HPD)-PRT with a chemotherapeutic agent, Cisplatin, against an experimental tumor (RIF-1) in an animal model. We have been unable to demonstrate an additive effect of laser HPD-PRT at total light doses of 25 J/cm2 and 75 J/cm2 with Cisplatin at a dose of 7 mg/kg. However, no additional toxicity was observed in combination therapy, suggesting that sequential application of laser HPD-PRT and Cisplatin may be safely employed in clinical situations. Another area of investigation has been the evaluation of the light-scattering characteristics of a lipid emulsion designed for laser HPD-PRT of bladder tumors. We have demonstrated that it is feasible to gain uniform illumination of the bladder surface with the use of this light-dispersing medium.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Laser photoradiation therapy of cancer: an update of the experience at the University of California, Irvine. 623 16

General immunobiologic studies in cancer patients have stressed measurements of lymphocyte function and have commonly ignored the monocyte-macrophage system. A preliminary study of peripheral blood monocyte-macrophage function was undertaken in a group of 90 cancer patients (18 breast, 32 colon, 13 head and neck, 9 lung, and 18 melanoma) and 70 controls. Studies included enumeration of extractible monocytes (EM), quantitation of differentiation into macrophages (macrophage precursor test: MP), evaluation of antibody-dependent cellular cytotoxicity (ADCC), and spontaneous cellular cytotoxicity (SCC) as measured with human erythrocytes, and measurements of monocyte and serum lysozyme activity. Breast cancer patients had normal profiles. Colon cancer patients showed the most profound abnormalities with decreased EM and MP and increased ADCC and SCC. Patients with Stage I and Stage II melanoma had normal profiles, whereas those with advanced melanoma had significantly decreased MP. This defect was restored in two patients by BCG immunotherapy. Head and neck cancer and benign breast disease patients had decreased EM, whereas patients with lung cancer had increased EM. Monocyte lysozyme production was unchanged in the cancer patients compared to controls. Serum lysozyme levels, however, were significantly increased in patients with cancers of the colon, head and neck, and lung. Although patients with localized breast cancer and melanoma had normal levels, these were increased in both patient groups with advanced disease. It would appear that the source of the increased serum lysozyme is probably not the peripheral blood monocytes, but could have originated in the intra-tumoral or tissue-bound macrophages which were not examined. Selected assays of peripheral blood monocyte function were deranged in certain types of cancer patients but were fully normal in others, and did not show consistent correlations with tumor type or stage. Tissue-bound or intra-tumoral macrophages might provide a more fruitful area for study in these disease categories.
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PMID:Monocyte dysfunction in human cancer. 682 39

Until now, there have not been any parameters to monitor opioid therapy in cancer patients with pain. In this study, 325 consecutive advanced cancer patients were scheduled for a prospective longitudinal survey. After exclusions, 67 patients were surveyed. All included patients were advanced cancer patients with pain that required opioid therapy for more than 6 weeks before death. Opioid escalation, symptoms associated with opioid therapy, pain mechanism, and pain intensity were recorded. Indices were calculated to categorize the response to opioids. The opioid escalation index (OEI) was used to index the mean increase of the starting opioid dosage, expressed as a percentage or in mg. The length of the period of stable dose (MLD) and the effective analgesic score (EAS), that is, the analgesic consumption/pain relief ratio calculated at fixed intervals, were also used. Patients with a mean visual analogue scale score (VAS) of less than 4 and regular OEI and EAS were considered responsive; patients with a mean VAS less than 4 but with an OEI more than 5 or increases of more than 100% of EAS when compared to that calculated the week before were considered mildly responsive; and patients with a mean VAS more than 4 were considered unresponsive. Advanced age, female gender, and previous chemotherapy were all factors reducing OEI. Head and neck cancer was associated with a higher OEI. Regarding the influence of the opioid-related symptoms, an increased OEI was associated with the presence of confusion. Moreover the presence of confusion was associated with neuropathic pain. Neuropathic pain taken alone, however, did not influence this score. Gender-specific cancer, such as breast cancer, influenced the gender differences reported for MLD (significantly longer than that reported for males and other primary tumor). Good responsiveness was observed in 28 patients, partial responsiveness in 33 patients, unresponsiveness in six patients. Psychological factors were associated with poor pain relief, probably reducing the patient's compliance. The tools used in this study may be useful in monitoring the effects of opioid therapy in cancer pain patients. Simple numbers are easy to compare and make it possible to profile opioid responsiveness and differences among patients.
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PMID:Monitoring of opioid therapy in advanced cancer pain patients. 913 31

The authors report that 4 out of a series of 56 patients (7.1%) treated with gemcitabine developed an unexplained non-cardiogenic pulmonary distress syndrome most likely related to gemcitabine. One further patient developed ventricular arrhythmia immediately after gemcitabine exposure, leading to cardiac arrest. Between 1995 and 1998 56 patients with locally advanced or metastatic carcinoma were treated with gemcitabine. The patients suffered from breast cancer (n = 17), pancreatic cancer (n = 17), lung cancer (n = 12), cancer of unknown primary (n = 5), ovarian cancer (n = 2), oral cavity cancer (n = 2) and cancer of the bladder (n = 1). Their median age was 55 years, and there were 33 female and 23 male patients. Fifteen patients had been pretreated with radiation therapy: 2 had received radiation therapy involving the mediastinum as treatment for non-small-cell lung cancer and cancer of unknown origin respectively, 11 patients had had prior neoadjuvant or adjuvant radiation therapy of the chest wall for breast cancer and 2 patients had received radiation therapy for head/neck cancer. All patients received gemcitabine on days 1, 8 and 15 and this was repeated on day 29 at a dose of 1000 mg/m(2) as a 30-min infusion in 250 ml isotonic NaCl. In 4 patients gemcitabine treatment was combined with cisplatinum, in 7 patients with a somatostatin analogue and in 1 patient with epirubicin. All other patients received gemcitabine as a single agent. We assume that the pulmonary or cardiac toxicity of 5 patients was related to gemcitabine. In 3 patients re-exposure resulted in repeated toxicity. One patient did not receive gemcitabine again because of the life-threatening nature of the primary response. Two patients had received prior radiation to the mediastinum with 62 Gy and 50 Gy respectively, 3 years and 1 year before gemcitabine application. In our experience pulmonary toxicity after gemcitabine treatment is more common than initially anticipated. Gemcitabine should be used with caution in patients who have received prior radiation to the mediastinum.
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PMID:Severe non-haematological toxicity after treatment with gemcitabine. 1054 71

Carcinoma cell lines are frequently refractory to transforming growth factor-beta (TGF beta)-mediated cell cycle arrest. Whether and how TGF beta signaling is disrupted in the majority of human tumors, however, remains unclear. To investigate whether TGF beta signaling might be disrupted by inactivation of the key signaling molecule, the TGF beta type I (T beta R-I) receptor, and whether or not T beta R-I inactivation is associated with late stage disease, we conducted a comprehensive structural analysis of the T beta R-I gene in fine-needle aspirates of 23 head-&-neck cancer metastases. We encountered 4 different mutations of T beta R-I, 3 of which have not been previously identified. In 1 case, we found a somatic intragenic 4-bp deletion predicting for a truncation of the receptor protein. This is the first example of a true loss-of-function mutation of T beta R-I in a human epithelial neoplasm. In 2 other cases, we identified missense mutations located between the juxtamembrane- and serine-threonine kinase domains. One of these resulted in an alanine-to-threonine substitution (A230T), which disrupts receptor signaling activity by causing rapid protein degradation within the endoplasmatic reticulum. This represents a novel mechanism of inactivation of a TGF beta signaling intermediate. Finally, we identified a serine-to-tyrosine substitution at codon 387 (S387Y) in a metastasis but not in the corresponding primary tumor. We had previously shown this S387Y mutant to be predominantly associated with breast cancer metastases and to have a diminished ability to mediate TGF beta-dependent signaling. In aggregate, these findings provide further support for the hypothesis that inactivation of the TGF beta signaling pathway occurs in a significant subset of human cancers.
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PMID:Novel inactivating mutations of transforming growth factor-beta type I receptor gene in head-and-neck cancer metastases. 1147 74

The advent of monoclonal antibodies targeted at tumor associated or tumor specific antigens provides a novel approach for the treatment of a broad range of malignancies. Such targeting agents can either be used as unlabeled molecules to induced antibody dependent cytotoxicity, or complement mediated lysis and/or apoptosis, or be conjugated with cytotoxic moieties such as toxins and/or radioactive nucleids. The applicability of this strategy has been expanded beyond the treatment of NHL as demonstrated by the clinical application of the chimeric monoclonal antibody directed at the Her2/neu receptor in breast cancer, the epidermal growth factor receptor in colon and head/neck cancer, and the vascular endothelial growth factor in lung and colon cancer, among others. In a variety of settings this strategy demonstrates clinical anti-tumor activity in patients who have failed to respond to or are refractory to conventional cytotoxic chemotherapy. Furthermore, given the modest toxicity of these naked antibodies, they avail themselves as ideal partners for combining with conventional chemotherapy to produce results that often appear to be greater than additive. With the discovery of newer targets and means to manipulate the immunoglobulin molecule to generate tailor made antibody fragments, the field of antibody based targeted therapy of cancer appears to be on the threshold of making major strides in the fight against cancer.
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PMID:Monoclonal antibody therapy of non-Hodgkin's lymphoma: the Rituximab story. 1274 5

Langmuir monolayers are useful models of biomembranes as they allow simulation of biological conditions and rigorous thermodynamic analysis. This technique was used to characterize tissues at body temperature for the first time in our study. The organs studied include liver, kidney, stomach, testis, heart and brain from goat and certain human cancerous as well as their corresponding normal biopsies to reveal the potential of the tissue monolayer technique. Monolayers were formed on the surface of deionized water by spreading monolayer amounts of the tissue homogenates. The parameters calculated were minimum surface tension, relative lift off area, relative limiting area, compressibility and hysteresis area. Our results reveal that the parameters can differentiate between tissues obtained from different organs and were statistically significant using one-way ANOVA and Newman Keul's test (P<0.05). For example goat's stomach tissue had the lowest hysteresis area (DeltaG) value (27.6 microJ) whereas brain DeltaG value was nine folds higher than stomach value. Brain had the lowest minimum surface tension of 30.3+/-1.0 mN/m whereas stomach had a value of 40.5+/-0. 2 mN/m. Interestingly, the DeltaG values of human normal neck and esophageal tissues were 3.4 and 3.2 folds greater than that of their respective cancer tissues whereas the DeltaG values of vulval and breast cancer tissues were 4.6 and 4 folds greater than that of their respective normal tissues. While the gammamin values of neck cancer tissue showed 95% increase from normal tissue values, those of vulval and breast cancer tissues were 46 and 50% less compared to their respective normal tissue values. Though all the surface tensiometric parameters showed significant changes, minimum surface tension and hysteresis area were the most sensitive indicators of tissue types and diseased states. Further, the effects of therapeutics could also be monitored by this technique. This is evidenced by the post-radiotherapy tissue isotherms of neck and vulval cancers, where clinical radio-sensitivity was associated with a shift in the tensiometry towards their respective normal isotherms. The small sample amounts required, precision of the technique, very low within group variability, organ specificity and sensitivity to detect changes in diseased states make it a promising tool for prognostic evaluation of diseased states and monitoring effects of therapeutics. Further research is warranted in this promising and hitherto unexplored field of tissue tensiometry.
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PMID:Dynamic surface tensiometry of tissues using Langmuir films. 1562 Aug 38

Gas7, a growth-arrest-specific protein, is expressed preferentially in the brain and is required for neurite outgrowth in cultured cerebellar and peripheral murine neurons. Gas7 interacts with F-actin and colocalizes with the terminal part of actin microfilament in cells in which membrane outgrowth is present. Gas7 isoforms were discovered in murine brain by alternative splicing. This work reports the identification of two human Gas7 cDNA: hGas7-a with 2,427 nucleotides, which encodes 330 amino acids, and hGas7-b with 2,610 nucleotides, which encodes 412 amino acids according to predicted open-reading-frames. The predicted hGas7-b protein is 97% homologous to murine homologues, whereas the hGas7-a is homologous to the mouse Gas7-cb form that is expressed preferentially in cerebellum. Alignment analysis of the Gas7 protein sequences revealed a high homology to that in humans: 99% for the monkey, 97% in murine, and around 75% for the puffer fish and chicken. The hGas7-b protein comprises a WW domain, which often associates with other domains that are typically present in proteins in signal transduction processes, and an FCH domain, which participates in rearranging the cytoskeleton. The hGas7-a comprises only the FCH domain. Analysis of the human Gas7 sequences using the DNA database revealed that the two forms resulted from the canonical alternative splicing of a Gas7 genomic sequence. The abundance of both hGas7 mRNA levels, determined by quantitative PCR in tissues including brain, breast cancer, placenta, and head-neck cancer, revealed that the level of hGas7-a was 14 times that of hGas7-b in these tissues. Transfection of cells with hGas7-a or hGas7-b cDNA yielded the predicted 38-kDa or 50-kDa protein, respectively. The ectopic expression of hGas7 caused neurite-like cell processes in both mouse Neuro-2a and human SH-SY5Y neuroblastoma cells. Interestingly, the hGas7-a preferentially elicited the small lamellipodia, whereas the hGas7-b elicited the small filopodia phenotype. These findings reveal the evolutionary conservation of the structure and function of Gas7. They also suggest that the FCH domain in Gas7 may participate in the development of lamellipodia, and the WW domain may participate in the fine-tuning of the filopodia.
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PMID:Human Gas7 isoforms homologous to mouse transcripts differentially induce neurite outgrowth. 1594 47


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