Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0016382 (flushing)
 6,387 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Resistance of hypoxic cells to radiation and chemotherapy remains a major limitation to effective therapy of solid tumors. Misonidazole, a 2-nitroimidazole analogue, has been studied extensively as a radiosensitizer of hypoxic cells and has been shown to undergo bioreductive metabolism to exert preferential cytotoxicity against hypoxic cells. We have investigated the effects of misonidazole on the biosynthesis of prostaglandins (PGs) in a murine mammary adenocarcinoma cell line (No. 4526) under aerobic and hypoxic conditions in attempts to exploit modulation of PG levels under hypoxia as a means of improving therapeutic approaches for the treatment of solid tumors. We report a time-dependent inhibition of PG biosynthesis by the suspended cells under hypoxia induced by flushing sealed vials with N2 (1.5 liters/min). After 30 min of hypoxia, PG formation was inhibited by 50%. Indomethacin was able to further inhibit the PG formation in a concentration-dependent manner under hypoxia. Misonidazole, however, selectively increased the PGE2 biosynthesis under hypoxia by 49% at 100 microM. This increase was concentration dependent over the range of 25 to 100 microM and was blocked by indomethacin (0.1 microM). Imidazole, the heterocyclic moiety in misonidazole without the nitro function, had no effect on PG biosynthesis at these concentrations. These data suggest that arachidonic acid metabolism is sensitive to the differential oxygen levels which exist within solid tumors and that PG levels may be modulated by electron-affinic agents in hypoxic tumor cells.
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PMID:Modulation of prostaglandin biosynthesis in hypoxic murine mammary adenocarcinoma cells by misonidazole. 273 27

Twenty-five patients with metastatic gastrointestinal adenocarcinoma received one to four infusions (400 mg) of murine monoclonal antibody CO17-1A. Eleven patients had mild gastrointestinal symptoms, and one had a transient flushing episode. Two of five who received three weekly infusions had readily reversible anaphylactic reactions at the time of the third infusion (day 15). There were no other toxic effects. One patient had a complete remission and is surviving at greater than 104 weeks, and four had stable disease. The median survival for the whole group was 57 weeks. In general, the antibody infusions were well tolerated but had modest antitumor effects.
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PMID:Phase I trial of multiple large doses of murine monoclonal antibody CO17-1A. I. Clinical aspects. 339 68

Antineoplaston A3 is an oxidated mixture of small peptides and amino acid derivatives isolated from human urine which have shown antineoplastic activity in tissue culture and low toxicity in mice. Twenty-four patients diagnosed with 25 cases of neoplastic diseases were involved in the studies. The patients' diagnoses included: adenocarcinoma of the prostate, stage IV (7 cases); adenocarcinoma of the breast, stage IV (3); adenocarcinoma of the colon and rectum, stage IV (3); adenocarcinoma of the colon, status post resection (1); adenocarcinoma of the lung, stage III (2); squamous cell carcinoma of the lung, stage III (2); adenocarcinoma of the pancreas, stages II and IV (2); and single cases of adenocarcinoma of the kidney, stage IV; malignant fibrohistiocytoma, stage IV; glioblastoma multiforme, stage IV; basal cell epithelioma; and transitional cell carcinoma of the bladder, grade II. Only patients who had over six weeks' anticipated survival and who continued the treatment for over six weeks were eligible. In 23 patients, Antineoplaston A3 was administered in divided doses daily i.v. through a subclavian vein catheter. In one patient, the injections were given i.m. The length of treatment was from 44 to 478 days and the highest dosage was 76 mg/kg/24 h. Side-effects associated with treatment included febrile reaction (4 patients), vertigo (2), headache (2), flushing of the face, nausea and tachycardia (1 each). Adverse reactions were mild and occurred only once during the entire course of treatment. Desirable side-effects included increase of platelet count, increase of white blood cell count and increase of reticulocyte count. At the end of the study, there were 5 cases of complete remission, 5 of partial remission, nine of stable disease and six of increasing disease. The patients who obtained complete remission were diagnosed with cancers of the bladder, prostate, colon, and basal cell epithelioma. In view of its very limited toxicity and the interesting responses obtained, Antineoplaston A3 was submitted for Phase II clinical trials to establish its usefulness in cancer treatment.
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PMID:Phase I clinical studies of antineoplaston A3 injections. 356 12

In this prospective study, we examined the possible diagnostic value of the measurement of two endometrial proteins, placental protein-14 (PP14) and CA-125, in the evaluation of pre- and post-menopausal bleeding. Concentrations of these two proteins were measured in plasma and uterine flushings obtained from 139 pre- and post-menopausal women with bleeding problems, and 26 normal post-menopausal control women without bleeding. Endometrial biopsy samples were also obtained for histological study. Concentrations of PP14 in both the plasma and uterine flushings in post-menopausal women were significantly lower (P < 0.001) than those of control pre-menopausal women. In post-menopausal women, the concentrations of PP14 (mean +/- SEM) in both plasma and flushing were significantly higher (P < 0.001) in women with endometrial adenocarcinoma (46.9+/-7.5 ng/ml plasma; 3350+/-1711 ng/ml flushing) than in the controls (7.6+/-1.3 ng/ml plasma; 125+/-27 ng/ml flushing) or in women with post-menopausal bleeding and atrophic endometrium (20.4+/-2.1 ng/ml plasma; 453+/-167 ng/ml flushing). In contrast CA-125 concentrations in plasma and flushings were similar in post-menopausal and pre-menopausal women. Plasma concentrations of CA-125 were higher in post-menopausal women with adenocarcinoma (29.1+/-7.4 IU/ml) than in those with post-menopausal bleeding and atrophic endometrium (21.8+/-2 IU/ml) (P < 0.05) or control post-menopausal subjects (16.1+/-2.1 IU/ml) (P < 0.01). CA-125 concentrations in uterine flushings were not significantly different in any group of post-menopausal women. The results show that concentrations of PP14 are correlated more strongly to endometrial histopathology than those of CA-125 in pre- and post-menopausal women. Elevated PP14 concentrations are also associated with the presence of endometrial adenocarcinoma and may have a potential to be used as a marker for this disease.
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PMID:Is the measurement of placental protein-14 and CA-125 in plasma and uterine flushings useful in the evaluation of peri-menopausal and post-menopausal bleeding? 980 52

Neuroendocrine tumors of the cervix are rare and are often under- or misdiagnosed. Because these tumors are very aggressive, early diagnosis and subsequent treatment are warranted. We describe a 46-yr-old woman with carcinoid syndrome caused by an atypical carcinoid of the uterine cervix. At age 44, she had dysplasia on Pap smear and underwent total abdominal hysterectomy with the diagnosis of adenocarcinoma. Fourteen months postoperatively, she developed the carcinoid syndrome and was found to have numerous liver metastases. Histological and immunohistochemical investigations of biopsy specimens from the patient's liver lesions and original cervical lesion ("adenocarcinoma") suggested that this woman had a primary atypical carcinoid of the uterine cervix with metastases to the liver. Treatment with octreotide and alkylating agents decreased the episodes of flushing and diarrhea within 8 weeks. If an adenocarcinoma of the uterine cervix is diagnosed, atypical carcinoid should be in the differential diagnosis. Symptoms of the carcinoid syndrome should be pursued and, if present, a urinary 5-hydroxyindolacetic acid level should be obtained. Timely diagnosis of a neuroendocrine tumor of the cervix may improve survival.
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PMID:Carcinoid syndrome caused by an atypical carcinoid of the uterine cervix. 1056 74

Epidemiology has demonstrated that alcoholic beverages are causally related to oropharyngolaryngeal, esophageal, liver, colorectal, and female breast cancer. Among Japanese male alcoholics screened by endoscopy combined with esophageal iodine staining and immunofecal occult blood tests, 4.2% had esophageal squamous cell carcinoma (SCC); 1.2%, oropharyngolaryngeal SCC; 1.4%, stomach adenocarcinoma; 1.9%, colorectal adenocarcinoma. The inactive form of aldehyde dehydrogenase-2 (ALDH2), encoded by the gene ALDH2*1/2*2, which is prevalent in Asians, exposes them to higher levels of acetaldehyde after drinking and was a strong risk factor for these cancers among Japanese heavy drinkers. Inactive ALDH2 was also associated with synchronous and metachronous multiple esophageal cancers. These results suggest a general role of acetaldehyde, an established animal carcinogen, in carcinogenesis of the human alimentary tract. The oropharyngolarynx and esophagus lack ALDH2 activity, suggesting that after exposure to acetaldehyde derived from systemic, mucosal, salivary, or bacterial production or alcoholic beverages, these organs' inefficient degradation of acetaldehyde enhances the chances for local acetaldehyde-associated carcinogenesis. The normal alcohol dehydrogenase-2 (ADH2), encoded by ADH2*1/2*1, is another risk factor for oropharyngolaryngeal and esophageal cancer in Japanese alcoholics. For patients with both normal ADH2 and inactive ALDH2, the risks for oropharyngolaryngeal and esophageal cancer are enhanced in a multiplicative fashion. The responses to a simple questionnaire about both current and past facial flushing after drinking a glass of beer can indicate an individual's ALDH2 phenotype fairly well. Use of this questionnaire to obtain information on ALDH2-associated cancer susceptibility could contribute to the prevention of alcohol-related cancer in Asians.
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PMID:[Alcohol and oropharyngolaryngeal and digestive tract cancer]. 1182 13

Immune heparin-induced thrombocytopenia (HIT) is a life-threatening adverse effect of heparin. It can result from any type of heparin exposure and by any route of administration; however only a few cases are reported after exposures to small quantities of heparin from catheter flushes. The major clinical problem associated with HIT is thrombosis. Early detection and institution of alternative, non-heparin anticoagulation are important. We report a patient with HIT associated with use of therapeutic-dose unfractionated heparin in whom immune sensitization to heparin was triggered by two 500-unit exposure to UFH associated with intravascular catheter flushing for antineoplastic chemotherapy in a patient with colon adenocarcinoma.
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PMID:Immune heparin-induced thrombocytopenia resulting from preceding exposure to heparin catheter flushes. 1717 92

The symptoms that result from compression of the superior vena cava are known as superior vena cava syndrome. The syndrome was originally described as secondary to infection such as tuberculosis or syphilitic aortic aneurysm. Currently, the origin is generally cancer or thrombotic events. Adenocarcinoma of the lung is the most common cause. Thrombotic causes are increasing because of the rise in use of pacemakers and central venous catheters for access or treatment purposes. Symptoms may include a feeling of fullness in the head, dyspnea, and cough. Clinical findings may include facial and neck swelling; dilated venous channels over the trunk, upper extremities, and neck; facial flushing; cyanosis; respiratory stridor and distress; and neurologic signs. Primary symptoms are in the neck and head. Treatment of superior vena cava syndrome will depend on the cause of the compression. If thrombosis is found, thrombolysis and anticoagulation may be indicated. With carcinoma or infection, specific drugs or radiation may be used. In cases of compression, dilation and stenting of the superior vena cava may be performed. In some cases a bypass of the superior vena cava may be indicated.
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PMID:Superior vena cava syndrome. 1732 62

Hypersensitivity reactions (HSR) to oxaliplatin in patients with colorectal cancer include facial flushing, erythema, pruritus, fever, tachycardia, dyspnea, tongue swelling, rash/hives, headache, chills, weakness, vomiting, burning sensations, dizziness, and edema. We report a patient with fever as the sole manifestation of initial HSR, review the literature and discuss the management of HSR. A 57-year-old female with T3N2M0 rectal adenocarcinoma received modified FOLFOX-6. She tolerated the first 8 cycles without any toxicities except grade 1 peripheral neuropathy and nausea. During 9th and 10th infusions, she developed fever to a maximum of 38.3 centigrade with stable hemodynamic status despite medications. During 11th infusion, she developed grade 3 HSR consisting of symptomatic bronchospasm, hypotension, nausea, vomiting, cough, and fever. On examination, she was pale, cyanotic, with a temperature of 38.8 centigrade, BP dropped to 95/43 mm Hg, pulse of 116/min and O(2) saturation of 88%-91%. She was hospitalized for management and recovered in 24 h. Fever alone is not a usual symptom of oxaliplatin HSR. It may be indicative that the patient may develop serious reactions subsequently, as did our patient who developed hypotension with the third challenge. Treatment and prevention consists of slowing the infusion rate, use of steroids and antagonists of Type 1 and 2 histamine receptor antagonists, whereas desensitization could help to provide the small number of patients who experience severe HSR with the ability to further receive an effective therapy for their colorectal cancer.
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PMID:Fever as the only manifestation of hypersensitivity reactions associated with oxaliplatin in a patient with colorectal cancer Oxaliplatin-induced hypersensitivity reaction. 1787 1

Iso-octyl chain-hydroxylated oxysterols were determined in attomoles per 10,000 cells concentrations in 10,000-80,000 cultured pancreatic adenocarcinoma cells, using a sensitive, highly automated nano-LC-ESI-MS-based method. Identified oxysterols included 24S hydroxycholesterol (24S-OHC), 25 hydroxycholesterol (25-OHC), and 27 hydroxycholesterol (27-OHC), while 20S hydroxycholesterol and 22S hydroxycholesterol were not detected. Lower mass limit of quantification was 23 fg (65 amol) for 25-OHC and 27-OHC (100 times lower than our previous method) and 54 fg (135 amol) for 24S-OHC, after derivatization into Girard T hydrazones and online sample cleanup using simplified and robust automatic filtration and filter back flushing solid phase extraction LC/MS/MS. The instrument configuration was easily installed using a commercial nano-LC/MS system. Recoveries in spiked sample were 96, 97, and 77% for 24S-OHC, 25-OHC, and 27-OHC, with within- and between-day repeatabilities of 1-21% and 2-20% relative SD, respectively. The study demonstrates the potential of nano-LC in lipidomics/sterolomics.
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PMID:Highly automated nano-LC/MS-based approach for thousand cell-scale quantification of side chain-hydroxylated oxysterols. 2479 27


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