Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An 84-year-old woman was admitted because of anemia and marked leukocytosis. The white cell count was 237,660/microliter, with 93% abnormal lymphoid cells. The cells had abundant cytoplasm and prominent nucleoli. They were positive for CD 5, 19, 20, 22, 23, HLA-DR, IgM, IgD and kappa chain. Thus, a diagnosis of B-cell PLL was made. Chromosome analysis disclosed a complex karyotypic abnormality. Massive splenomegaly was detected by abdominal computed tomography. No external or internal lymphadenopathy was found. The patient was intermittently treated with etoposide. Although the white cell counts had been suppressed, she refused to take the drug because of side effects. When the white cell count exceeded more than 200,000/microliter again, she developed severe headache, diplopia, nausea, and vomiting. A lumber puncture disclosed infiltration of the prolymphocytes in the cerebrospinal fluid. Though intrathecal chemotherapy alleviated the symptoms and the leukemic cells disappeared, the effects were transient. When the therapy was withheld because of bone marrow suppression, the meningitis recurred and the symptoms progressed. The patient died six months after the initial presentation.
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PMID:[Leukemic meningitis in B-cell prolymphocytic leukemia]. 1222 29

Chemotherapy and radiation therapy for cancer often have severe side effects that limit their efficacy. Glucocorticoids (GCs) are frequently used as cotreatment because they may have potent proapoptotic properties and reduce nausea, hyperemesis, and acute toxicity on normal tissue. In contrast to the proapoptotic effect of GCs in lymphoid cells, resistance toward cancer therapy-mediated apoptosis was induced in solid tumors of human cervix and lung carcinomas. Filter hybridization, expression data, as well as functional assays identified multiple core apoptosis molecules, which are regulated by GCs in a pro- or antiapoptotic manner. Both antiapoptotic genes such as FLIP and members of the Bcl-2 and IAP family as well as proapoptotic elements of the death receptor and mitochondrial apoptosis pathways were down-regulated in carcinomas resulting in a decreased activity of caspase-8, caspase-9, and caspase-3. In contrast, death receptor and mitochondrial apoptosis signaling as well as caspase activity was enhanced by dexamethasone in lymphoid cells. To restore apoptosis sensitivity in dexamethasone-treated carcinomas, caspase-8 and caspase-9 were transfected. This resensitized tumor cells in vitro and xenografts in vivo to cisplatin induced cell death. These data therefore raise concern about the widespread combined use of GCs with antineoplastic drugs or agents in the clinical management of cancer patients.
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PMID:Glucocorticoid cotreatment induces apoptosis resistance toward cancer therapy in carcinomas. 1281 Jun 37

Bortezomib (Velcade, formerly PS-341) is proteasome inhibitor with documented antitumor activity in multiple myeloma and other lymphoid malignancies. We performed a Phase I study to investigate the maximum tolerated dose and dose-limiting toxicity of bortezomib in patients with acute leukemias refractory to or relapsing after prior therapy. Fifteen patients were treated with 0.75 (n = 3), 1.25 (n = 7), or 1.5 (n = 5) mg/m(2) bortezomib administered twice weekly for 4 weeks every 6 weeks. Dose-limiting toxicity included orthostatic hypotension (n = 2), nausea (n = 2), diarrhea (n = 1), and fluid retention (n = 1), all at 1.5 mg/m(2) bortezomib. Proteasome inhibition was dose dependent and reached 68% at 1.5 mg/m(2) bortezomib. Peak inhibition was observed 1 h after treatment and returned to near baseline levels by 72 h after treatment. Incubation of blast cells with bortezomib in vitro showed induction of apoptosis in three of five patients investigated. We conclude that the maximum tolerated dose of bortezomib in patients with acute leukemia is 1.25 mg/m(2), using a twice-weekly for 4 weeks every 6 weeks schedule. The in vitro evidence of antileukemia and transient hematological improvements observed in some patients warrants further investigation of bortezomib in acute leukemias, probably in combination with other agents.
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PMID:Phase I study of bortezomib in refractory or relapsed acute leukemias. 1516 91

Low-grade lymphoma arising in mucosa-associated lymphoid tissue (MALT) of the duodenum represents a very rare neoplasm. We report an unusual presentation of primary duodenal MALT lymphoma in a 78-year-old man. The patient initially presented with a suspected pulmonary embolus and was anticoagulated, which precipitated a major gastrointestinal hemorrhage. A large atypical ulcer with narrowing of the duodenum beyond the bulb was seen on endoscopy. Biopsies revealed atypical lymphoid cells. Abdominal CT scan revealed a mass in either the duodenum or head of the pancreas. An endoscopic retrograde cholangiopancreatography (ERCP) was performed, which revealed a normal pancreatic duct with a large calculus in the common bile duct, which was extracted after sphincterotomy. Elective surgery was planned for suspected lymphoma of the duodenum. The patient developed severe nausea, vomiting, and fullness after meals. The patient underwent pancreaticoduodectomy for a neoplastic mass causing duodenal obstruction. Pathological examination of the resected specimen revealed a low-grade B-cell lymphoma (MALToma) arising in the duodenum and invading the pancreas. Flow cytometry confirmed the phenotype typical of MALT lymphoma. Celiac, peripancreatic, pelvic, and cervical nodes were also involved with tumor. Bone marrow was also positive for metastasis. The patient was postoperatively treated with chemotherapy for stage IV disease.
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PMID:Primary duodenal low-grade mucosa-associated lymphoid tissue lymphoma presenting with outlet obstruction. 1527 85

The glucocorticoid dexamethasone is frequently used as co-treatment in cytotoxic cancer therapy, e.g. to prevent nausea, to protect normal tissue or for other reasons. While the potent pro-apoptotic properties and the supportive effects of glucocorticoids to tumour therapy in lymphoid cells are well studied, the impact to cytotoxic treatment of colorectal and hepatocellular carcinoma is unknown. We tested apoptosis-induction, viability, tumour growth and protein expression using 8 established cell lines, 18 surgical specimen and a xenograft on nude mice. In the presence of dexamethasone we found strong inhibition of apoptosis in response to 5-FU, cisplatin, gemcitabine or gamma-irradiation, enhanced viability and tumour growth of colorectal and hepatocellular carcinomas. No correlation with age, gender, histology, TNM, the p53 status and induction of therapy resistance by dexamethasone co-treatment could be detected. These data show that glucocorticoid-induced resistance occurs not occasionally but is common in colorectal and hepatocellular carcinomas implicating that the use of glucocorticoids may be harmful for cancer patients.
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PMID:Dexamethasone desensitizes hepatocellular and colorectal tumours toward cytotoxic therapy. 1633 63

The glucocorticoid dexamethasone is frequently used as a co-treatment in cytotoxic cancer therapy, e.g. to prevent nausea, to protect normal tissue or for other reasons. While the potent pro-apoptotic properties and supportive effects of glucocorticoids to tumour therapy in lymphoid cells are well studied, the impact on the cytotoxic treatment of ovarian carcinoma is unknown. We tested apoptosis-induction, viability, tumour growth and protein expression using established cell lines, primary cell lines freshly isolated from patient material and a xenograft on nude mice. We found a general induction of resistance toward cytotoxic therapy by DEX-co-treatment in most of the examined ovarian cancer cells treated in vitro, ex vivo or in vivo. Resistance occurred independently of cell density and was found at peak plasma levels of dexamethasone and below. Mechanistically, the dexamethasone-induced expression of survival genes may be involved in the resistance. These data show that glucocorticoid-induced resistance is common in ovarian carcinomas implicating that the use of glucocorticoids may be harmful for cancer patients.
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PMID:Glucocorticoid-mediated inhibition of chemotherapy in ovarian carcinomas. 1639 12

Total body irradiation (TBI) is an important part of bone marrow transplantation conditioning regimens. In TBI, dose escalation is difficult, because of associated normal organ toxicities. A method to deliver a more targeted dose of TBI preferentially to sites of greatest tumor burden is needed to reduce the dose to normal organs, reduce toxicities, and permit dose escalation. The purpose of this study was to evaluate, through a dosimetric analysis, the potential advantages and feasibility of selectively delivering targeted myeloablative doses of radiation to bone and marrow using a recently developed image-guided tomographic intensity-modulated radiation therapy delivery system (helical tomotherapy). Whole-body computed tomography datasets from 3 patients, age 5, 20, and 53 years, were used for treatment planning studies to evaluate 2 targeted TBI strategies: total marrow irradiation (TMI), in which the target region was defined as the skeletal bone, and total marrow and lymphoid irradiation (TMLI), in which the target regions were defined as bone, major lymph node chains, liver, spleen, and sanctuary sites, such as brain. Organ doses and dose distributions were compared with those in conventional TBI. A 1.7- to 7.5-fold reduction in median organ doses was observed with TMI and TMLI compared with conventional TBI. With this more targeted approach, a dose-volume histogram analysis predicted the potential to escalate the dose to bone (and containing marrow) up to 20 Gy, while maintaining doses to normal organs at lower levels than in conventional TBI to 12 Gy. Results were similar for the adult and pediatric patients, indicating that this form of targeted TBI will be applicable to most patients regardless of frame size. TMI to 10 Gy was delivered as part of a tandem transplant regimen to the 53-year-old patient with multiple myeloma. Clinical results confirmed the treatment planning predictions. After TMI, the patient experienced the expected blood count nadir, followed by successful engraftment. Grade 2 nausea and grade 1 emesis occurred only briefly on day 2 of TMI. Skin erythema, oral mucositis, esophagitis, and enteritis were not observed. This report demonstrates the feasibility and potential dosimetric advantages of selectively delivering myeloablative doses of radiation to bone and marrow using an image-guided tomographic intensity-modulated radiation therapy delivery system. Organ doses are substantially lower than those associated with standard TBI and predict the potential to significantly reduce associated toxicities and allow for dose escalation. The results also suggest that this form of targeted TBI may have potential advantages over other forms of targeted TBI, such as radioimmunotherapy or bone-seeking radionuclide therapy. Ongoing clinical trials will define the maximum TMI and TMLI doses achievable and define the potential advantages and limitations of this new approach for patients undergoing hematopoietic stem cell transplantation.
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PMID:Targeted total marrow irradiation using three-dimensional image-guided tomographic intensity-modulated radiation therapy: an alternative to standard total body irradiation. 1650

Glucocorticoids have been used widely in conjunction with other treatment for patients with cancer because they have potent proapoptotic properties in lymphoid cells, can reduce nausea, and alleviate acute toxic effects in healthy tissue. However, glucocorticoids are used in a supportive-care role, even though to our knowledge no prospective clinical studies have assessed the effect of these steroids on the growth of solid tumours. Data from preclinical and, to some extent, clinical studies, suggest that glucocorticoids induce treatment resistance in solid tumours, including prostate cancer. Research has focussed on disseminated cells that have been shed by the tumour: the potential of glucocorticoids to render these cells resistant to apoptosis--and to downregulate the immune response--might contribute to tumour metastasis. Here, we review the benefits of glucocorticoids and their negative effects, such as induction of resistance in tumour cells and concomitant induction of apoptosis in immune cells, with particular emphasis on prostate cancer.
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PMID:Glucocorticoid use in prostate cancer and other solid tumours: implications for effectiveness of cytotoxic treatment and metastases. 1664 47

We reported a case of X-linked lymphoproliferative syndrome (XLP) with multiple nodular lesions in the brain and lungs. A 21-year-old man was admitted because of one month history of low grade fever, headache, nausea, and amnesia. He developed agammaglobulinemia following Epstein-Barr virus infection at 3-year-old, and thereafter was administered 7.5g of immunoglobulin every 3 weeks with a diagnosis of XLP. Physical examination was unremarkable on admission. Neurological examination revealed disorientation of time, and bilateral gaze-evoked nystagmus. Neuropsychological tests demonstrated impairment of recent memory and calculation. Pleocytosis (83/microl) and increase of protein (1269 mg/dl) and IgG (141 mg/dl) in the CSF were observed. Brain MRI showed multiple nodular lesions with high intense signal on T2-weighted images and Gd-DTPA enhancement on T1-weighted images. Chest CT showed multiple nodular lesions in the bilateral lungs. The needle lung biopsy was performed, which showed infiltration of lymphocytes around the vessels. An immunohistochemical study showed that the infiltrating cells were mainly CD8 positive T lymphocytes. B lymphocyte and plasma cells were not seen. The histological findings excluded intravascular malignant lymphoma and lymphomatoid granulomatosis. Therefore we diagnosed lymphoid vasculitis. The patient developed pancytopenia caused by hemophagocytic syndrome 48 days after admission and was treated with 1 g of methylprednisolone per day for 3 days and a tapered dose of steroid (500 mg to 125 mg of methylprednisolone and 60 mg to 10mg of predonisolone) for 21 days, which resulted in the improvement of clinical features (hemophagocytic syndrome and central nervous system symptoms) and the abnormal CSF findings. The multple nodular lesions in the brain and the lungs shrank 1 month after treatment and disappeared 11 months later. There are few reports concerning lymphoid vasculitis with XLP, and no effective treatment has been described. Our case suggests that steroid therapy may be useful for the treatment of lymphoid vasculitis in XLP.
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PMID:[Case of X-linked lymphoproliferative syndrome (XLP) with multiple nodular lesions in the brain]. 1676 91

Glucocorticoids (GCs) such as dexamethasone (DEX) have been widely used as co-medication in cancer therapy because they have potent proapoptotic properties in lymphoid cells, can reduce nausea, and alleviate acute toxic effects in healthy tissue. However, GCs are used in a supportive-care role, even though no prospective clinical studies have assessed the effect of these steroids on the growth of solid tumours. Data from preclinical and, to some extent, clinical studies, suggest that GCs induce treatment resistance in some solid tumours. Since it is unknown whether GC-induced resistance occurs only occasionally or is a more common phenomenon, we performed a screening study using several established cell lines from bone, brain, breast and cervix carcinoma as well as melanoma and neuroblastoma together with fresh surgical resections from patients with breast cancer. We found that DEX inhibits cisplatin and 5-fluorouracil-induced apoptosis and promotes the growth of the majority of examined malignant cells. In contrast, and as expected, DEX acted pro-apoptotically and promoted the cytotoxic effect of chemotherapy in established and primary lymphoid cells. Thus, these data demonstrate the need for detailed molecular studies to clarify the mechanism of differential glucocorticoid signaling as well as controlled, prospective clinical studies.
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PMID:Corticosteroids induce chemotherapy resistance in the majority of tumour cells from bone, brain, breast, cervix, melanoma and neuroblastoma. 1701 64


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