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)

Once thought to be a relatively untreatable disease, pancreatic cancer has recently become a focus of intense clinical research. The systemic administration of gemcitabine (Gemzar) is currently considered the standard first-line treatment for patients with advanced disease. While treatment with gemcitabine has been shown to result in both clinical benefit and prolongation of survival, objective tumor responses are relatively uncommon and median survival times remain short. Several recent efforts have therefore focused on evaluating chemotherapy regimens in which gemcitabine is combined with other cytotoxic drugs. While randomized trials have now confirmed that such combinations are associated with higher response rates, they have not yet clearly demonstrated that combination therapy results in a survival advantage. Increasingly, attention has turned to a number of novel chemotherapeutic and biologic agents that appear promising and are likely to play an important future role in the treatment of patients with this disease.
 ...
PMID:Advanced pancreatic cancer: is there a role for combination therapy? 1459 95

Erlotinib (Tarceva) is an orally available selective small-molecule inhibitor of HER1/EGFR tyrosine kinase with a 50% inhibitory concentration of 2 nM for purified tyrosine kinase. This agent has been shown to produce stasis or regression of tumor growth in human cancer xenograft models, including non-small-cell lung cancer models. Ongoing preclinical investigations indicate that inhibition of the MAPK and Atk signaling pathways downstream of HER1/EGFR may be required for optimal antitumor effects. Erlotinib exhibits inhibition of MAPK and Atk kinases at concentrations higher than those required for HER1/EGFR tyrosine kinase inhibition; such findings suggest that maximal inhibition of HER1/EGFR, requiring high erlotinib doses, is necessary for optimum antitumor activity. These considerations are supported by tumor models, including non-small-cell lung cancer models, showing dose-related antitumor effects up to high doses of erlotinib. Erlotinib exhibits additive antitumor effects when combined with chemotherapeutic agents (cisplatin, doxorubicin, paclitaxel, gemcitabine [Gemzar], and capecitabine [Xeloda]), radiation therapy, and other targeted agents (e.g., bevacizumab [Avastin]). Recent studies indicate that erlotinib inhibits the EGFRvIII mutant at concentrations higher than those required for inhibition of wild-type receptor. Ongoing investigation will help to determine optimal dosing and dose frequency of erlotinib in various cancers in the clinical setting.
 ...
PMID:Erlotinib: preclinical investigations. 1468 18

Of the new chemotherapeutic substances of the last decade, gemcitabine (Gemzar, Eli Lilly) is probably the most valuable for the treatment of early and advanced stage non-small cell lung cancer (NSCLC). When used as a single agent in both chemotherapeutically pretreated and chemotherapy-naive patients, gemcitabine shows an objective tumor regression rate of approximately 20%. Gemcitabine's unique mechanism of action and its lack of overlapping toxicity with other cytotoxic agents also define it as an ideal candidate for combination therapy. Early clinical development has included single-agent first- and second-line treatment, doublet combination regimens and incorporation into multimodality treatment strategies for operable and inoperable locally advanced nonmetastatic NSCLC. Gemcitabine/platinum-based combination chemotherapy has become the most attractive treatment standard for NSCLC patients in good clinical condition. The role of gemcitabine in the concurrent or sequential application of chemo- and radiotherapy for inoperable locally advanced NSCLC has also been addressed in several Phase I and II studies. Based on data available, gemcitabine can be safely administered in combination with radiotherapy. This review summarizes results from representative Phase I, II and III studies in order to underline gemcitabine's clinical importance for patients suffering from early and advanced NSCLC.
 ...
PMID:Gemcitabine (Gemzar) in non-small cell lung cancer. 1516 34

Chemotherapy (CT) for elderly patients is becoming a standard, since the first demonstration by Gridelli and co-workers that chemotherapy (in their case Vinorelbine (VNB), single agent) is capable to produce significant survival benefits. Much less is known concerning the use of CT for unfit patients. The purpose of this phase II trial was to perform a comprehensive evaluation of activity, toxicity, and tolerability of single-agent Gemcitabine (GEM) (Gemzar) as a first-line chemotherapy for unfit patients with inoperable or recurrent non-small cell lung cancer. Patients were eligible if they had a pathological diagnosis and no previous chemotherapy; they should be younger than 76, with a performance status (ECOG-PS) equal to three; informed consent was also required. Gemcitabine was given by intravenous infusion at a weekly dose of 1250 mg/m2, 3 weeks per month, every 28 days. Treatment was given until progression, persistent toxicity, or refusal. Forty-five patients (39 males) entered the study; median age was 73 years (range 45-75); cell types were: adenocarcinoma (21), squamous (18), large cell (6). Previous surgical treatments included three lobectomies and one pneumectomy. Because of rapid clinical deterioration or consent withdrawal, six patients, registered for study, never started their treatment; other six had early chemotherapy suspension. These patients were included in the analysis, on an "intent-to-treatment" basis. The median number of chemotherapy cycles was nine (range 0-15); median dose-intensity was 75% of projected. Toxicity was mild, mainly hematological and never life threatening (only 1 grade 4 toxicity out of 325 pre-chemotherapy evaluations). Four patients obtained a partial response (9%, C.I. 1-17%) and other six patients had some tumor regression (13%, C.I. 3-23%). The estimated median time to progression was 17 weeks (quartile range: 9-24), with a median survival of 35 weeks (quartile rage: 20-51). We have found that single-agent gemcitabine represent a sufficiently safe therapeutic option in unfit patients with inoperable non-small cell carcinoma (NSCLC).
 ...
PMID:Front-line weekly chemotherapy with gemcitabine for unfit patients with non-small cell lung cancer (NSCLC). 1530 78

Several new antimetabolites, administered alone or in combination, are changing the therapeutic landscape for thoracic cancer. Two-drug combinations involving these newer drugs are becoming the standard of care for non-small-cell lung cancer (NSCLC), largely due to improvements in survival rates, time to disease progression, and response rates as well as an improved safety profile. Gemcitabine (Gemzar) has elicited considerable interest in this disease, as a combination partner in chemotherapeutic regimens. Another promising agent is pemetrexed (Alimta), a folate-based inhibitor of thymidylate synthase. In preclinical development, pemetrexed both alone and in combination with other cytotoxic agents has exhibited activity across a broad range of tumor models, including NSCLC and mesothelioma. In clinical trials of patients with NSCLC, pemetrexed has been an effective, well-tolerated agent that can be used as monotherapy or in combination with other agents at full dose. In clinical trials of patients with mesothelioma, the combination of pemetrexed and cisplatin demonstrated a significant improvement in survival, response, and patient quality-of-life parameters. The principle toxicities of pemetrexed can be minimized by folate and vitamin B12 supplements.
 ...
PMID:New investigative regimens and cytotoxic agents in thoracic cancers: gemcitabine and pemetrexed. 1533 53

The use of chemotherapy in the treatment of early and advanced non-small-cell lung cancer (NSCLC) has increased during the past decade. One of the main reasons for the increased acceptance of chemotherapy is the development of several new cytotoxic agents with a unique mechanism(s) of action and high single-agent activity, combined with a favorable toxicity profile. Pemetrexed (Alimta) is a novel antifolate that inhibits several enzymes involved in DNA synthesis (thymidylate synthase [TS], dihydrofolate reductase [DHFR], and glycinamide ribonucleotideformyltransferase [GARFT]). Pemetrexed's toxicity is markedly reduced by folic acid and vitamin B12 supplementation. The compound has been studied extensively in various tumor types, including NSCLC. In NSCLC, pemetrexed at 500 mg/m2, every 3 weeks, given i.v. over 10 minutes, has shown promising activity, and can safely be administrated with vitamin supplementation. After registration, single-agent pemetrexed will certainly add to the chemotherapeutic options available for pretreated patients and will most likely change significantly chemotherapy prescriptions in second-line chemotherapy. In first-line chemotherapy, the role of platinum-based and -free combination doublet chemotherapy with pemetrexed still needs to be defined. Phase II data indicate high efficacy combined with favorable toxicity for pemetrexed in combination with cisplatin, carboplatin (Paraplatin), oxaliplatin (Eloxatin), gemcitabine (Gemzar), and vinorelbine (Navelbine). This review summarizes the clinical experience obtained thus far during the early clinical development of pemetrexed in NSCLC.
 ...
PMID:Pemetrexed: its promise in treating non-small-cell lung cancer. 1533 59

Effects of gemcitabine (Gemzar) on immune cells were examined in pancreas cancer patients to determine whether it was immunosuppressive, or potentially could be combined with vaccines or other immunotherapy to enhance patient's responses to their tumors. Blood was obtained at five time-points, before therapy, 3-4 days after initial gemcitabine infusion and immediately preceding three additional weekly infusions. Effects on T-cell subsets, B-cells, myeloid dendritic cell precursors, antigen presenting cells (APC), activated/memory, and naive cells were examined. Functional activity was measured by intracellular staining for cytokines before and after T-cell activation, and by interferon gamma production in EliSpot responses to tumor presentation. Although absolute lymphocyte counts decreased with the initial treatment with gemcitabine infusion, the counts stabilized during subsequent treatments, then returned within normal ranges seven days after the fourth treatment so that the absolute lymphocyte count no longer differed significantly from that prior to treatment. These effects on absolute lymphocyte counts were mirrored by statistically significant decreases in absolute numbers of CD3 and CD20 lymphocytes during these time periods. The proportions of T and B-cells, however did not change significantly with therapy, although significance changes were observed in some specialized subsets. A decrease in the proportions of the major BDCA-1+, CD1b myeloid dendritic cell subset and a reciprocal increase in the minor BDCA-3+ dendritic cell subsets resulted at 3-4 days, then their levels returned to normal. No significant changes in percentages of CD86 and CD80 APCs or CD4+, CD25+ T-cells were documented. Increased percentages of CD3+, CD45RO+ memory lymphocytes reached significance at day 7, then declined to statistically significant decrease at days 14 and 21 after the second and third infusions, respectively. Immune T-cells were functional in pancreas cancer patients treated with gemcitabine. The data suggest that gemcitabine therapy may decrease memory T-cells and promote naive T-cell activation. We conclude that gemcitabine therapy (1) is not immunosuppressive and (2) may enhance responses to specific vaccines or immunotherapy administered to activate or support immune responses directed toward driving effector immunity to cancer cells.
 ...
PMID:Effect of gemcitabine on immune cells in subjects with adenocarcinoma of the pancreas. 1578 12

We isolated and screened two tumor cell clones DD1 and DG6 with different capacity of metastasis from the same parent cell line, a mouse dendritic cell (DC) sarcoma, using limited dilution method. The genome-wide expressions of DD1 and DG6 cells were detected by Affymetrix's MOE-430A microarray. The expression profiles related with mouse DC development were downloaded from GEO at NCBI and ArrayExpress at EBI database. In order to compare the expression of DC sarcoma and DC developmental arrays which was performed by MG-U74av2, we had screened the best matched probesets between MOE-430A and MG-U74av2 according to the probe identities from Affymetrix technical annotation. After the normalization of 11 housekeeping genes across the 34 arrays (2 DC sarcoma and 32 DC developmental arrays), all these expression profiles were analyzed by the methods of hierarchical clustering, principal component analysis, nearest-neighborhood, and self-organizing maps. The results indicate that expression profiles of DC sarcoma are closer to those of the DC progenitors and hematopoietic stem cells from bone marrow compared with the sorted DCs from spleen. The results support the hypothesis that cancers (tumors or sarcomas) arise from stem cells. It is suggested that the DC sarcomas are more similar to the DC progenitors and hematopoietic stem cells than the relative mature DCs in gene expressions on the large-scale.
 ...
PMID:Expression profiles of mouse dendritic cell sarcoma are similar to those of hematopoietic stem cells or progenitors by clustering and principal component analyses. 1584 78

A novel gemcitabine-lipid conjugate 5 was synthesized and tested for its in vivo efficacy and toxicity. Compound 5 was tested in BxPC-3 human pancreatic tumor model in SCID mice and exhibited promising activity and lower toxicity when compared with Gemzar.
 ...
PMID:Synthesis and biological evaluation of gemcitabine-lipid conjugate (NEO6002). 1586 18

The article is dedicated to a new method of treatment of pancreatic cancer, developed by researchers of St. Petersburg Research Institute of Roentgenology and Radiotherapy. The method consists in slowing down blood flow in the tumor by means of selective embolization of its arteries using a mixture of the chemiotherapeutic agent gemcitabine (Gemzar) in the oily radio-paque medium Lipodol Ultrafluid. Upon entering microcirculatory vessels, the agent diffuses into pancreatic tissue. This tumor chemoinfiltration provides prolonged contact between tumor tissue and the chemoembolization agent, thus allowing strong antitumor effect without high systemic toxicity. Experimental studies on 12 dogs have proved that oil arterial chemoembolization with lipiodol does not cause morphological changes in the pancreas, and is only manifested by short and reversible hyperenzymemia.
 ...
PMID:[Radiopaque oil chemical arterial embolization in treatment of pancreatic cancer]. 1614 30


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