Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0013395 (dyspepsia)
 4,879 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

High-dose thymidine (dThd) was given to 12 patients with advanced hematological and solid tumors. The dose schedule used was 75 g/sq m/day, given i.v. continuously for 5 days or more. Myelosuppression, especially leukopenia, was the dose-limiting toxicity. Nonhematological toxicities affected the gastrointestinal tract (nausea, vomiting, anorexia, diarrhea, and indigestion) and the central nervous system (somnolence, headache, visual illusions, and memory impairment). Patients who had received cumulative doses of dThd developed alopecia. Thymine crystals were noted in the urine after refrigeration. Tumor regression (less than partial remission) occurred in one patient with melanoma. Three of four patients with acute leukemia had a fall in peripheral white blood cell counts and blasts but no marrow improvement. Four patients with adenocarcinoma (three colon, one unknown primary) had stable disease. Pharmacokinetic studies revealed that, at a dThd dose of 75 g/sq m/day, millimolar concentrations of dThd and thymine can be achieved in the plasma. The half-life of dThd was approximately 100 min. One-third of the plasma concentrations was measurable in the cerebrospinal fluid. dThd was mainly excreted by the kidneys.
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PMID:Clinical phase I-II and pharmacokinetic study of high-dose thymidine given by continuous intravenous infusion. 747 Oct 98

An 89-year-old woman was seen for indigestion, light chest pain, and melanotic stools. Endoscopic examination revealed 2 submucosal gastric masses. A subtotal gastrectomy showed 2 submucosal masses in the stomach: one infiltrating through the muscularis propria into the serosa, the second one, a well-circumscribed submucosal nodule. Histologic examination showed large tumor cells infiltrating diffusely through the muscularis propria into the subserosa. On higher magnification, numerous signet ring cells were present against a myxoid stroma, in addition to large vacuolated epithelioid cells. There was no evidence of invasion, necrosis, nuclear pleomorphism, or mitotic activity. Initial diagnostic considerations based on the histology included signet ring cell carcinoma, malignant melanoma, and a myxoid mesenchymal tumor, including gastrointestinal stromal tumor. A panel of immunohistochemical stains showed diffuse strong positivity for S-100 protein and negative reaction for CD117, bcl-2, cytokeratin AE1/AE3, Melan-A, HMB45, smooth muscle antigen, and other differentiation markers. Electron microscopic examination revealed elongated, complex, and interdigitating cell processes covered by a thin layer of continuous basement membrane material characteristic of peripheral nerve sheath differentiation. The presentation of this tumor was significant in that it was multifocal and infiltrative, mimicking a malignant neoplasm. The extensive myxoid/signet ring cell change represents a heretofore-unreported histologic variant of gastric schwannoma.
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PMID:Signet ring cell gastric schwannoma: report of a new distinctive morphological variant. 1832 78

Immune checkpoint inhibitors such as programmed cell death-1 inhibitor pembrolizumab have been shown to be effective in metastatic malignancies such as advanced melanoma. Immune-related adverse effects on multiple organs have been described, such as colitis, skin rash, and hypothyroidism. We present the case of a 44-year-old man with advanced melanoma and recurrent lung metastases who developed symptoms of dyspepsia and gastroesophageal reflux disease after 1 month of therapy with pembrolizumab. Gastric biopsy showed histologic features consistent with lymphocytic gastritis, which was absent on a biopsy 2 months before initiation of therapy. Lymphocytic infiltrates likely secondary to increased autoimmunity after use of immunotherapy have been observed in the colon; however, such histologic findings in the upper gastrointestinal tract have yet to be described. Here, we present a case of lymphocytic gastritis in a patient treated with pembrolizumab, suggesting a new manifestation of toxicity.
Melanoma Res 2018 12
PMID:Lymphocytic gastritis induced by pembrolizumab in a patient with metastatic melanoma. 3025 71

The peel of Citrus unshiu Marcow. fruits (CU) has long been used as a traditional medicine that has therapeutic effects against pathogenic diseases, including asthma, vomiting, dyspepsia, blood circulation disorders, and various types of cancer. In this study, we investigated the effect of CU peel on metastatic melanoma, a highly aggressive skin cancer, in B16F10 melanoma cells, and in B16F10 cells inoculated-C57BL/6 mice. Our results show that ethanol extracts of CU (EECU) inhibited cell growth and increased the apoptotic cells in B16F10 cells. EECU also stimulated the induction of mitochondria-mediated intrinsic pathway, with reduced mitochondrial membrane potential and increased generation of intracellular reactive oxygen species. Furthermore, EECU suppressed the migration, invasion, and colony formation of B16F10 cells. In addition, the oral administration of EECU reduced serum lactate dehydrogenase activity without weight loss, hepatotoxicity, nor nephrotoxicity in B16F10 cell-inoculated mice. Moreover, EECU markedly suppressed lung hypertrophy, the number and expression of metastatic tumor nodules, and the expression of inflammatory tumor necrosis factor-alpha in lung tissue. In conclusion, our findings suggest that the inhibitory effect of EECU on the metastasis of melanoma indicates that it may be regarded as a potential therapeutic herbal drug for melanoma.
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PMID:Citrus unshiu peel suppress the metastatic potential of murine melanoma B16F10 cells in vitro and in vivo. 3148 24