Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A phase I-II clinical trial was conducted to determine the maximum-tolerated dose (MTD) of oral cyclosporine (CsA) and vinblastine in patients with metastatic renal cell cancer (RCC) as well as to estimate the response rate. Sixteen patients received a 5 mg/kg oral loading dose of CsA followed by 3 days of CsA in 4 divided daily doses escalating from 10 mg/kg per day up to 17 mg/kg per day. Vinblastine (Vbl) was administered as an intravenous bolus on the morning of the 3rd day with dose escalation from 6 to 10 mg/m2. Cycles were repeated every 4 weeks until tumor progression. Forty-nine cycles of CsA with vinblastine were administered. The maximum tolerated dose of Vbl was 10 mg/m2, with neutropenia as the dose-limiting toxicity resulting in one death. CsA could not be escalated above 17 mg/kg per day because of nausea and vomiting. Other toxicities included constipation (100%), malaise (100%), temporary increase in pain (36%), and one seizure that may have been drug-related. There were no clinically significant changes in renal function or serum bilirubin. Mean peak whole-blood CsA level at the highest CsA dose level was 919 ng/ml (range: 414-1,827) with a trough prior to Vbl injection of 451 ng/ml (range: 128-1,229). There were no tumor responses. The combination of oral CsA and Vbl is not nephrotoxic but is poorly tolerated. In most patients optimal blood levels of CsA for reversal of MDR cannot be reliably achieved, and vinblastine dose intensity must be compromised because of the significant toxicity of this regimen.
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PMID:Phase I-II study of vinblastine and oral cyclosporin A in metastatic renal cell carcinoma. 774 14

We first describe a case of generalized intraperitoneal seeding of hepatocellular carcinoma (HCC) after microwave coagulation therapy (MCT). A 61 year-old man underwent operative MCT for an exophytic HCC, 60 mm in diameter, in segment IV of his cirrhotic liver. Despite successful tumor ablation, the serum alpha-fetoprotein levels continuously rose after MCT. Five months later, radiographic examinations delineated several perihepatic masses with hypervascularity, and the patient presented with constipation. At the second laparotomy, there were numerous small peritoneal metastases involving the entire peritoneal cavity and slightly bloody ascites. An omental mass, 50 mm in diameter, involved the transverse colon. Most of these intraabdominal masses were removed together with the involved colon. Histologically, the initial tumor was a moderately differentiated HCC, and the peritoneal masses were poorly differentiated HCCs. The patient died of rapid tumor progression and bleeding 2 months later. In conclusion, we should be aware of the possible occurrence of peritoneal seeding after MCT for HCC. Every effort should be made to prevent this serious complication, particularly in cases of superficial, large, and less differentiated HCCs.
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PMID:Generalized intraperitoneal seeding of hepatocellular carcinoma after microwave coagulation therapy: a case report. 1052 41

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.
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PMID:Thalidomide for the treatment of multiple myeloma. 1532 81

In the present article, we have summarized the phase I/II clinical trials on combination therapy of S-1 and docetaxel. With result of the phase I study, patients were treated with intravenous infusion of 40 mg/m2 docetaxel on day 1 and oral S-1 80 mg/m2/day on days 1 to 14 every 3 weeks. Forty eight patients received a total of 272 treatment cycles. No complete responses (CRs) and 27 partial responses (PRs) were observed for an overall response rate (CR+PR) of 56.2% (95% CI, 38-66%). Eighteen patients (37.5%) had stable disease (SD), and 3 patients (6.2%) had progressive disease (PD) as best response. The tumor control rate (CR+PR+SD) was 93.8% (95% CI, 83-98%). The median overall survival was 14.3 months (95% CI: 10.7-20.3 months) and the median time to tumor progression was 7.3 months (95% CI: 4.2-10.7 months). The most common grade 3-4 hematologic toxicities were neutropenia 58.3%, leukopenia 41.7%, febrile neutropenia 8.3%, and anemia 8.3%. The most common grade 3 nonhematologic toxicities were anorexia 14.6%, stomatitis 8.3%, nausea 6.3%, diarrhea 4.2%, constipation 4.2%, and vomiting 2.1%. No grade 4 nonhematologic toxicities were reported, and all treatment-related toxicities were resolved. The mechanisms underlying these synergistic effects of S-1 and docetaxel were examined by expression and activity analyses of 5-FU metabolic enzymes. The expressions of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) were decreased and that of orotate phosphorybosyl transferase (OPRT) was increased in mRNA, protein level and activity assay after the treatment with docetaxel and 5-FU in the TMK-1 gastric cancer cell. These findings strongly indicate that the combination chemotherapy of docetaxel and S-1 is effective against gastric carcinomas and therefore is a good candidate as a standard chemotherapeutic strategy in treating these tumors.
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PMID:[Combination chemotherapy of S-1 and docetaxel on advanced and recurrent gastric cancer]. 1689 78

Tendencies to suppress negative emotions have been shown to predict adjustment to cancer and cancer progression. We examined whether emotional suppression, in terms of both general and emotion-specific tendencies, predict symptom reports, mood states, and coping appraisals during adriamycin/doxorubicin, cyclophosphamide/cytoxan chemotherapy for breast cancer. Forty participants completed a measure yielding scores for anxiety suppression, anger suppression, depression suppression, and total emotional suppression. They then reported their experiences of 34 physical symptoms, mood, and coping efficacy on a daily basis for the duration of treatment (84 days). Mixed model analyses revealed that emotional suppression predicted lower reports of symptoms that are vague, well-known, and potentially embarrassing side effects of chemotherapy (e.g., fatigue and constipation). Emotional suppression and particularly anger suppression predicted higher reports of symptoms relating to immune function and cardiovascular arousal (e.g., mouth sores and heart palpitations) and with appraisals of poorer coping. The three suppression tendencies exhibited distinctive patterns of relationships with symptoms, mood, and coping appraisals, suggesting that anxiety suppression, anger suppression, and depression suppression have partially independent relationships with symptomatic and mood processes. The findings highlight the potential importance of emotional suppression for understanding symptom and coping responses during chemotherapy.
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PMID:Emotional suppression tendencies as predictors of symptoms, mood, and coping appraisals during AC chemotherapy for breast cancer treatment. 2065 65

Mu opioids are among the most widely used drugs for patients with cancer with both acute and chronic pain as well as in the perioperative period. Several retrospective studies have suggested that opioid use might promote tumor progression and as a result negatively impact survival in patients with advanced cancer; however, in the absence of appropriate prospective validation, any changes in recommendations for opioid use are not warranted. In this review, the authors present preclinical and clinical data that support their hypothesis that the mu opioid receptor is a potential target for cancer therapy because of its plausible role in tumor progression. The authors also propose the hypothesis that peripheral opioid antagonists such as methylnaltrexone, which reverses the peripheral effects of mu opioids but maintains centrally mediated analgesia and is approved by the US Food and Drug Administration for the treatment of opioid-induced constipation, can be used to target the mu opioid receptor.
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PMID:The mu opioid receptor: A new target for cancer therapy? 2604 35