Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although thalidomide was withdrawn in the 1960s after its teratogenic property was recognized, it was subsequently found that this drug possesses immunomodulatory and anti-inflammatory effects. Recent studies have also demonstrated that thalidomide has antineoplastic activity via an antiangiogenic mechanism. Observations in the late 1990s that the microenvironment in the bone marrow plays a role in tumor progression in multiple myeloma provided an impetus to use thalidomide for the treatment of this disease. It is known that thalidomide monotherapy is effective in one-third of refractory cases, and in combination with glucocorticoids and/or antineoplastic drugs, thalidomide provides a response rate of more than 50%. Thus, thalidomide therapy is considered a standard approach for the treatment of relapsed and refractory myeloma. The exact mechanism of the antimyeloma effect of thalidomide is not yet clearly understood. Anti-angiogenic effects, direct activity in tumor cells such as the induction of apoptosis or G1 arrest of the cell cycle, the inhibition of growth factor production, the regulation of interactions between tumor and stromal cells, and the modulation of tumor immunity have been considered as possible mechanisms. In addition to its teratogenicity, the adverse effects of thalidomide have been general symptoms such as somnolence and headache, peripheral neuropathy, constipation, skin rash, and other symptoms. Although these adverse effects are generally reversible and mild, grade 3 and 4 toxicities such as peripheral neuropathy, deep venous thrombosis, neutropenia, and toxic dermal necrosis have occasionally been reported. The application of thalidomide therapy in patients with multiple myeloma is being broadened to include not only cases of refractory myeloma, but also previously untreated cases, as well as for maintenance therapy after hematopoietic stem cell transplantation and for the treatment of other hematological diseases. The safe use of this drug will depend on the establishment of diagnostic and treatment guidelines. In addition, the establishment of a nation-wide regulation system is urgently needed in Japan.
 ...
PMID:Thalidomide for the treatment of multiple myeloma. 1532 81

A woman affected by Cushing's disease underwent bilateral adrenalectomy followed by radiotherapy of the hypothalamic-pituitary area when she was 18 years old. Thereafter, she used hydrocortisone acetate replacement therapy (35.5 mg divided into two daily doses). At the age of 26 years, the patient exhibited the clinical signs of the Nelson's syndrome, i.e. skin and gingival hyperpigmentation accompanied by amenorrhea, and elevated ACTH plasma levels (2,850 pg/ml, normal range 15-80 pg/ml). The magnetic resonance imaging (MRI) analysis of the sellar region evidenced a pituitary macroadenoma, measuring 14 x 13 mm. The patient was initially treated with cyproheptadine hydrochloride (12 mg/day) for 18 months. There was a partial improvement of the symptoms, with a reduction of the ACTH plasma levels to 112 pg/ml, but without any modification of the tumor mass. Due to sleepiness and weight gain, the cyproheptadine treatment was interrupted and substituted by a cabergoline (0.5 mg twice a week) therapy. Soon after cabergoline was applied an improvement of the clinical symptoms and signs was observed such as a regression of the tumor mass and the normalization of the ACTH plasma titers (38 pg/ml). Later, cabergoline was substituted by bromocriptine (7.5 mg/day) and the plasma levels of ACTH increased again (247 pg/ml), and headache and cutaneous hyperpigmentation were recorded. When cabergoline was reintroduced there was a clinical improvement and normalization of ACTH plasma levels (64 pg/ml). The MRI analysis of the sella region demonstrated a complete remission of the pituitary adenoma. The results obtained show for the first time that a long-term treatment with cabergoline also brings about a complete remission of Nelson's syndrome in the presence of a pituitary macroadenoma.
 ...
PMID:Nelson's syndrome: complete remission with cabergoline but not with bromocriptine or cyproheptadine treatment. 1555 61

Two cases are reported where significant narrowing of the upper airway in association with narcotic administration resulted in respiratory compromise and death. Case 1: A 29-year-old woman with upper airway narrowing due to tonsillar enlargement from an Epstein-Barr infection was admitted to hospital, administered morphine and left in a room on her own with the door closed. She was found dead several hours later. At autopsy there was significant narrowing of the upper airway due to tonsillomegaly with a blood morphine level of 0.16 mg/L. Case 2: A 48-year-old woman with severe narrowing of her glottic inlet from recurrent squamous cell carcinoma and an intravenous drug taking history was found dead at her home. At autopsy there was evidence of recent and remote intravenous drug administration with marked narrowing of the glottis due to a recurrent tumor with a blood morphine level of 0.48 mg/L. In both cases, death was due to the effects of severe upper airway narrowing in combination with the respiratory depressant actions of morphine. Additional exacerbating factors may have included muscle weakness, drowsiness and reduced clearance of airway secretions from the effects of morphine. Narcotic administration in individuals with compromised upper airways should be undertaken extremely circumspectly and hospital protocols should ensure constant surveillance if this has been undertaken. Individuals who self administer narcotics should also be made aware of the dangers if there is coincidental upper airway narrowing. Toxicological evaluation in fatal cases of upper airway narrowing/stenosis may be extremely useful in revealing compounding factors such as opiate administration.
 ...
PMID:Narcotic administration and stenosing lesions of the upper airway--a potentially lethal combination. 1576 87

Thalidomide has been reported to yield anti-tumor activity in advanced renal cell carcinoma (RCC). We evaluated safety and efficacy of a combination therapy comprising interleukin (IL)-2 and thalidomide in patients with metastatic RCC refractory to both immuno- and chemotherapy. Twelve patients with progressive metastatic RCC who had failed prior treatment with immunochemotherapy and desired further active therapy were enrolled in this study. Oral thalidomide was started at 200 mg/day and escalated after 2 days to 400 mg/day at week 0. IL-2 at 7 MIU/m was given by s.c. injection, starting at week 1, days 1-5, weeks 1-4, with rest from IL-2 at weeks 5 and 6. Response was assessed every two therapy cycles. Ten patients were evaluable for response. There was no objective response; four patients showed stable disease for 14+, 11+, 10+ and 9 months, respectively. Toxicities were predominantly grade I-II, and included somnolence and constipation, as well as flu-like symptoms associated with IL-2. However, one patient developed serious constipation which led to a paralytic ileus and discontinuation of treatment. Another patient left the study after 7 weeks due to increasing disorientation/confusion. Eight patients required IL-2 dose reduction. Time on therapy ranged from 3 to 44 weeks (median 20 weeks). Median overall survival was 12+ months. At present, all patients have discontinued treatment. We conclude that outpatient administration of thalidomide/IL-2 is feasible in patients with heavily pretreated and progressive RCC who desire further active treatment. However, toxicity and costs are considerable, and clinical benefit is uncertain. Therefore, thalidomide/IL-2 might not represent a promising therapeutic approach for this subgroup of patients.
 ...
PMID:Application of thalidomide/interleukin-2 in immunochemotherapy-refractory metastatic renal cell carcinoma. 1584 24

Experimental studies have demonstrated that thalidomide has anti-tumor activity mediated by blockage of angiogenesis, with clinical efficacy in multiple myeloma, glioblastoma multiforme, and renal cell cancer. We investigated the therapeutic activity and toxicity of thalidomide in patients with progressive metastatic breast cancer pretreated with chemotherapy. Inclusion criteria were metastatic breast cancer in progression of disease after at least two lines of chemotherapy, age > or = 18 years, performance status < or = 2, and adequate hematologic, renal, and hepatic functions. Twelve patients entered the study, eight of whom were pretreated with three or more lines of chemotherapy (66.7%). Thalidomide was well tolerated: the most common side effects were constipation and somnolence (58.3% of patients). No objective response or durable stable disease was observed. Median time to progression and median overall survival were 8 weeks (range, 4-10 weeks) and 16 weeks (range, 8-54 weeks), respectively. In conclusion, thalidomide is an ineffective treatment in patients with progressive metastatic breast cancer heavily pretreated with chemotherapy.
 ...
PMID:Thalidomide is inactive in heavily pretreated patients with metastatic breast cancer. 1605 69

N-methyl-D-aspartate (NMDA) receptor antagonists enhance opioid-induced analgesia. The plasma concentration of ketamine, an NMDA receptor antagonist that enhances epidural morphine-and-bupivacaine-induced analgesia, is not known. We examined 24 patients with lung carcinoma or metastatic lung tumor who underwent video-assisted thoracic surgery in a placebo-controlled, double-blind manner 4 h after emergence from anesthesia. The morphine + ketamine group (n = 8) and morphine + placebo group (n = 8) received 5 mL volume of 2.5 mg morphine and 0.25% bupivacaine and the placebo + ketamine group (n = 8) received 5 mL volume of saline and 0.25% bupivacaine epidurally at the end of skin closure. Four hours after this anesthesia, in the morphine + ketamine and placebo + ketamine groups, ketamine was administered to successively maintain a stable plasma ketamine concentration of 0, 10, 20, 30, 40, and 50 ng/mL by a target-controlled infusion device, and patients assessed the levels of pain at rest, pain on coughing, somnolence (drowsiness), and nausea using a 100-mm visual analog scale (VAS). In the morphine + placebo group, a placebo (saline) was similarly administered instead of ketamine. In the morphine + ketamine group, the VAS scores for pain at rest and pain on coughing significantly decreased on ketamine administration at a plasma concentration of 20 ng/mL or larger compared with the respective baseline VAS scores (P < 0.05 each). In the placebo + ketamine group, the VAS scores for pain at rest and pain on coughing did not significantly change at any plasma concentration of ketamine as compared to the morphine + placebo group. In the morphine + ketamine group, a plasma concentration of ketamine larger than 20 ng/mL did not further reduce VAS scores for pain at rest and pain on coughing. The VAS scores for drowsiness were comparable among the three groups at any plasma concentration of ketamine. Ketamine at a plasma concentration of 20 ng/mL or larger may enhance epidural morphine-and-bupivacaine-induced analgesia. As an adjunct with epidural morphine-and-bupivacaine and considering the safety of small doses, the minimal plasma concentration of ketamine given IV may be approximately 20 ng/mL.
 ...
PMID:Determining the plasma concentration of ketamine that enhances epidural bupivacaine-and-morphine-induced analgesia. 1611 91

We report two children with post radiation midbrain damage causing severe neurological symptoms. A twelve-year-old boy with a four year history of hydrocephalus was diagnosed with tectal glioma, which endoscopic biopsy revealed to be low grade. He underwent gamma knife radiation surgery (central 24 Gy/peripheral 12 Gy). Two months later bilateral ptosis followed by total oculomotor palsy and drowsiness developed. Despite pulsed-steroid therapy the tumor size increased up to 4.6 times in volume. The tumor was totally removed and was diagnosed as an early delayed radiation reaction pathologically. His symptoms disappeared except for a slight upper gaze palsy. The second patient was a six-year-old girl with a medulloblastoma. Following total resection and a VP shunt she received conventional radiation therapy along with chemotherapy. After the final irradiation she became comatose (JCS II-2) and MRI revealed diffuse midbrain damage with acute aqueduct obstruction, which recovered in two weeks. Reports of irradiation injuries of the midbrain in childhood are rare but it should be considered as a possible cause of fulminant symptoms requiring emergency treatment. Because of midbrain anatomical complexity, midbrain radiation therapy requires great care, especially in children.
 ...
PMID:[Fulminating midbrain irradiation injury of pediatric brain tumor]. 1624 69

This unusual mixed glioneuronal neoplasm of the spine resembling central neurocytoma is only the second reported example of a neoplasm of this type involving the spinal cord and is, seemingly, the first to present with diffuse leptomeningeal dissemination and communicating hydrocephalus. This 15-month-old boy presented with somnolence, bilateral sixth nerve palsy, and lower-extremity weakness and was found to harbor a primary neoplasm within the thoracic spine and associated syrinx, widespread leptomeningeal dissemination, and communicating hydrocephalus. The patient underwent cerebrospinal fluid shunt placement, thoracic laminectomy for tumor debulking and biopsy, chemotherapy, and radiation therapy to the neuraxis. Immunohistochemically, the tumor was marked by evidence of mixed glial (glial fibrillary acidic protein-positive) and neuronal (synaptophysin-positive) differentiation. Mitotic activity was inconspicuous. No areas of vascular proliferation, necrosis, or marked nuclear pleomorphism were noted. Mixed glioneuronal neoplasms are a heterogeneous group of tumors whose biological potential remains incompletely defined. The present case illustrates the reality that some of these neoplasms can be clinically aggressive, despite comparatively bland histological features. The authors' goal is to acquaint neurosurgeons with the expanding spectrum of mixed glioneuronal neoplasms and with the potential of some of these lesions to pursue an aggressive clinical course.
 ...
PMID:Neurocytoma-like neoplasm of the thoracic spine in a 15-month-old child presenting with diffuse leptomeningeal dissemination and communicating hydrocephalus. Case report. 1637 Feb 89

Hypoglycemia is a well-known paraneoplastic manifestation of hepatocellular carcinoma usually occurring in the terminal stages of the disease. However, during initial presentation this manifestation is uncommon. We report a 77-year-old man who presented with signs and symptoms of severe hypoglycemia for example drowsiness. After clinical work-ups, we detected a large mass in the liver. Interestingly, after surgical excision of the tumor, the attacks of decreased level of consciousness and hypoglycemia seized.
 ...
PMID:Hypoglycemia, the first presenting sign of hepatocellular carcinoma. 1653 4

Seizures are a common complication of primary (PBT) and metastatic (MBT) brain tumors, affecting approximately 50% of all patients during the course of their illness. Anti-convulsant therapy of these tumor-induced seizures is often inadequate with conventional anti-epileptic drugs (AEDs), due to a variety of factors, including activation of glutaminergic NMDA receptors, immune-mediated neuronal damage, and anatomic alterations of neuronal input pathways. Levetiracetam (LEV) is a new AED with a novel mechanism of action, which includes reducing the Ca++ current through neuron-specific, high voltage activated Ca++ channels (n-type). Because of this unique mechanism, it has been postulated that LEV may be effective in controlling tumor-induced seizures. A retrospective chart review was performed of all patients who had received LEV for seizure control. Forty-one patients were reviewed (22 female, 19 male), with a median age of 47.5 years (range 25-81). There were 34 patients with PBT and 7 with MBT. LEV was used as an add-on AED in 33 patients and as monotherapy in eight patients, with a median dose of 1500 mg/day (range 500-3500). The baseline median seizure frequency for the cohort was 1 per week. After the addition of LEV and follow-up for a minimum of 4 weeks, the median seizure frequency was reduced to 0 per week (59% of patients noted complete seizure control). Overall, the seizure frequency was reduced in 90% of patients (P<0.0001; Sign test). The most common toxicity was somnolence, noted in 37% of patients. LEV was very effective and well tolerated in brain tumor patients with seizures, and should be considered for add-on therapy to current AEDs, or as a substitute anti-convulsant for monotherapy.
 ...
PMID:Retrospective analysis of the efficacy and tolerability of levetiracetam in brain tumor patients. 1654 29


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>