Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0684249 (lung carcinoma)
 23,830 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The combination of gemcitabine and cisplatin is one of the most active chemotherapy regimens against non-small cell lung cancer (NSCLC). This study was designed to evaluate the efficacy and safety of gemcitabine combined with cisplatin in a 3-week cycle regimen for patients with operable, early stage NSCLC. Gemcitabine at a dose of 1000 mg/m(2) on days 1 and 8 of each 21-day cycle for 3 cycles, followed by cisplatin at a dose of 75 mg/m(2) on day 1 was administered to patients with previously untreated, operable, early stage (IB-IIIA) NSCLC. A total of 47 patients (46 male, mean age 56.0+/-8.0 years) who met the eligibility criteria were enrolled. The pathological complete response rate was 5.3% of operated patients and 4.3% of total patients. At visit 4, 57.1% of the patients had partial response, 38.1%, stable disease and 4.8%, progressive disease. The main toxicities - leukopenia, neutropenia and thrombocytopenia - were usually clinically asymptomatic and did not require hospitalization. Non-hematological toxicities were minimal and manageable. Disease free and 12-month overall survival rates were over 70% and 80%, respectively. This study demonstrates that the administration of gemcitabine and cisplatin combination for 3 cycles is effective and tolerable for patients with operable, early stage NSCLC. Low toxicity profile and promising survival outcome suggest that this regimen has an encouraging activity in this subset of patients.
Lung Cancer 2007 Nov
PMID:Gemcitabine and cisplatin as neo-adjuvant chemotherapy for non-small cell lung cancer: a phase II study. 1768 27

Gemcitabine is a chemotherapeutic drug widely used in the treatment of non-small cell lung carcinoma, especially in advanced lung adenocarcinoma. However, many patients with advanced lung adenocarcinoma show a resistance to gemcitabine. Overexpression of COX-2 has been found in human non-small cell lung cancer tissues and itA s cell lines. Evidences show that COX-2 is involved in drug resistance of tumor. However, It is unknown whether COX-2 inhibitor can augment the efficacy of gemcitabine against lung adenocarcinoma. In this study, A549 cells were treated with gemcitabine and/or NS-398. The cell viability was examined by MTT assay. The cell cycle distribution and apoptotic ratio were tested by flow cytometry. The levels of p21WAF1, p27KIP1, p16INK4a and p15INK4b expression were detected by western blotting. After the cells were treated with gemcitabine along with NS-398, more cells were arrested in G1 phase and went to apoptosis. The levels of p21WAF1 and p27KIP1 protein were elevated, while the levels of p16INK4a and p15INK4b protein were not changed. It can be concluded that NS-398 enhances the efficacy of gemcitabine against lung adenocarcinoma and the efficacy is associated with up-regulation of p21WAF1 and p27KIP1protein.
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PMID:NS-398 enhances the efficacy of gemcitabine against lung adenocarcinoma through up-regulation of p21WAF1 and p27KIP1 protein. 1834 52

Concurrent chemoradiotherapy (CCR) followed or preceded by full-dose chemotherapy seems to be a standard treatment for unresectable non-small cell lung cancer (NSCLC). Gemcitabine is a strong radiosensitizer, and a phase I study confirmed the feasibility of CCR with low-dose gemcitabine administered twice-weekly in NSCLC patients. Consequently, we designed a prospective, multicentric, phase II trial to evaluate the efficacy and toxicity of this approach, following induction chemotherapy with cisplatin and gemcitabine. We included patients with unresectable stage III NSCLC, no pleural effusion, adequate pulmonary, renal, liver and hematological functions, Karnofsky index >70 and planned treated volume (PTV) <2200cm3. Treatment consisted of 3 cycles of cisplatin (100mg/m2, d1) and gemcitabine (1250mg/m2, d1 and 8) q3w, followed by CCR (gemcitabine 50mg/m2 on Mondays and Thursdays and radiotherapy 68.4Gy, 1.8Gyqd). After the inclusion of 22 patients (group A), an unacceptable toxicity was detected. Thus, cisplatin dose was reduced to 70mg/m2, and gemcitabine dose was adjusted to 35mg/m2 during CCR. Another 34 patients (33 eligible, group B) were included. Five patients in group A and 6 patients in group B discontinued the study treatment during induction. Thus, 17 and 27 patients, respectively initiated CCR. Hematological toxicity (grades III and IV) was particularly relevant in group A during this phase, with 35 and 23% of thrombopenia and neutropenia, respectively. Nonhematological grades III-IV toxicity of chemoradiation was significant and similar in groups A and B: esophagitis 35.2 and 33.3% and pneumonitis 23.5 and 25.9%, respectively. 40.9% of patients in group A vs. 57.5% in group B completed treatment. Overall response (intention-to-treat analysis) was 68.1% in group A and 63.5% in group B. Median survival was 17.7 months for the whole group with a mean follow-up of 41.2 months. 20% of patients were alive at 3 years. Long-term results of this schedule are encouraging. However, nonhematological toxicity of chemoradiation is substantial and different strategies should be tested to minimize it.
Lung Cancer 2008 Oct
PMID:Induction chemotherapy with cisplatin and gemcitabine followed by concurrent chemoradiation with twice-weekly gemcitabine in unresectable stage III non-small cell lung cancer: final results of a phase II study. 1844 89

Gemcitabine (Gemzar) is a nucleoside analogue used as a cytotoxic agent for the treatment of various carcinomas: pancreatic cancer, bladder cancer, breast cancer, and non-small-cell-lung cancer. Carboplatin, a DNA alkylating agent, is used alongside with gemcitabine in a regimen known as GemCarbo chemotherapy to treat several different types of cancer, most commonly lung cancer. We report an unusual case of hand-foot hyperpigmentation after the use of GemCarbo therapy on a man with stage IV non-small cell lung carcinoma. Physical examination revealed hyperpigmented lesions that were approximately 1-2 mm in diameter, of brown/purple discoloration localized to the palmar surface of his hands and the dorsum of his feet. A rapid plasma reagin blood test, used for the screening of syphilis was nonreactive. Discontinuation of both agents resulted in the dramatic disappearance of the lesions over the course of 2 weeks. In this report, we describe, to our knowledge, the first case of hand-foot hyperpigmentation that has been reported with the use of either of these 2 agents.
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PMID:Hand-foot hyperpigmentation skin lesions associated with combination gemcitabine-carboplatin (GemCarbo) therapy. 2046 Sep 84

The term "Pseudocellulitis" can be used to describe an uncomplicated nonnecrotizing inflammation of the dermis and hypodermis from a noninfectious etiology. Chemotherapeutic agents have been associated with a variety of cutaneous reactions, including radiation recall dermatitis, hypersensitivity reactions, and erysipeloid reactions. Gemcitabine (2,2-difluorodeoxycytidine) is currently being used for treatment of a variety of solid malignancies, including carcinoma of the lung. The dermatitis involved with gemcitabine is typically a radiation recall reaction whereby an inflammatory reaction occurs in the area previously treated with radiotherapy. We describe here a case of Gemcitabine-induced pseudocellulitis that was unrelated to radiation exposure and manifested in an area of lymphedema. The pseudocellulitis in such cases could be related to the drug's pharmacokinetics and may last until the drug is displaced from the subcutaneous tissue of the affected area. Antibiotics have no role in the treatment, and diphenhydramine with nonsteroidal anti-inflammatories may be used for symptomatic management.
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PMID:Recurrent lower extremity pseudocellulitis. 2277 33

A 62-year-old male presented with stage IV lung adenocarcinoma with leptomeningeal metastases (LM). Gemcitabine (1000 mg/m2 i.v.) was administered on days 1 and 8 while oxaliplatin (100/m2 i.v.) was administered on day 1 and repeated for 4 cycles every 3 weeks. Computerized tomography (CT) and cerebrospinal fluid (CSF) were used to evaluate the response of the LM and the primary tumor to drug therapy. Following the administration of chemotherapy, headaches were observed to be notably reduced 6 days later and absent after 14 days. The symptoms of coughing and chest pain were alleviated. Subsequent to 4 cycles of treatment, the patient had a partial response (PR) and the CSF pressure was normal. Analysis of the CSF revealed that it was colorless, positive for protein, had a total cell number of 0/l and contained no cancer cells. However, the primary lung tumor progressed for 1 year. This may suggest that first-line therapies, including the use of gemcitabine and oxalipaltin, may be appropriate for the treatment of non-small cell lung carcinoma (NSCLC) with LM involvement.
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PMID:Gemcitabine plus oxaliplatin for the treatment of leptomeningeal metastases of non-small cell lung cancer: A case report and review of the literature. 2376 May 44

With standard doublet chemotherapy for patients with advanced non-small-cell lung cancer (NSCLC), we have reached an outcome plateau of about 10 months median overall survival over the last decades. Several studies have now demonstrated some survival benefits for patients treated beyond induction chemotherapy. In the current discussion about treatment duration, the terms "switch" and "continuation" maintenance therapy are now most commonly used by the scientific community. Switch maintenance is the treatment with an agent with a different mode of action after completion of induction chemotherapy in patients who's tumors have not progressed, whereas continuation maintenance is the continuation of one compound of the induction regimen. Chemotherapeutic compounds successfully investigated in the maintenance setting are Gemcitabine, Docetaxel and Pemetrexed. Targeted agents, recently investigated as maintenance therapy are Bevacizumab, Cetuximab and Erlotinib. New peer-reviewed publications of phase III randomized clinical trials on maintenance chemotherapy have led to a change in current practice guidelines and the use of maintenance therapy represents a new treatment option in advanced NSCLC. The pivotal trials are described and summarized in this review article.
Transl Lung Cancer Res 2012 Jun
PMID:Maintenance therapy in non-small-cell lung cancer. 2580 66

Gemcitabine is a pyrimidine nucleoside analog that becomes triphosphorylated intracellularly where it competitively inhibits cytidine incorporation into DNA strands. Another mechanism-of-action of gemcitabine (diphosphorylated form) involves irreversible inhibition of the enzyme ribonucleotide reductase thereby preventing deoxyribonucleotide synthesis. Functioning as a potent chemotherapeutic gemcitabine promote decreases in neoplastic cell proliferation and apoptosis which is frequently found to be effective for the treatment of several leukemias and a wide spectrum of carcinomas. A brief plasma half-life in part due to rapid deamination and chemotherapeutic-resistance restricts the utility of gemcit-abine in clinical oncology. Selective "targeted" delivery of gemcitabine represents a potential molecular strategy for simultaneously prolonging its plasma half-life and minimizing innocient tissues and organ systems exposure to chemotherapy. The molecular design and an organic chemistry based synthesis reaction is described that initially generates a UV-photoactivated gemcitabine intermediate. In a subsequent phase of the synthesis method the UV-photoactivated gemcitabine intermediate is covalently bonded to a monoclonal immunoglobulin yielding an end-product in the form of gemcitabine-(C4-amide)-[anti-HER2/neu]. Analysis by SDS-PAGE/chemiluminescent auto-radiography did not detect evidence of gemcitabine-(C4-amide)-[anti-HER2/neu] polymerization or degradative fragmentation while cell-ELISA demonstrated retained binding-avidity for HER2/neu trophic membrane receptor complexes highly over-expressed by chemotherapeutic-resistant mammary adenocarcinoma (SKBr-3). Compared to chemotherapeutic-resistant mammary adenocarcinoma (SKBr-3), the covalent immunochemotherapeutic, gemcitabine-(C4-amide)-[anti-HER2/neu] is anticipated to exert greater levels of cytotoxic anti-neoplastic potency against other neoplastic cell types like pancreatic carcinoma, small-cell lung carcinoma, neuroblastoma, glioblastoma, oral squamous cell carcinoma, cervical epitheliod carcinoma, or leukemia/lymphoid neoplastic cell types based on their reported sensitivity to gemcitabine and gemcitabine covalent conjugates.
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PMID:Synthesis of Gemcitabine-(C4-amide)-[anti-HER2/neu] Utilizing a UV-Photoactivated Gemcitabine Intermediate: Cytotoxic Anti-Neoplastic Activity against Chemotherapeutic-Resistant Mammary Adenocarcinoma SKBr-3. 2622 16

Gemcitabine (GEM) is an anticancer agent widely used in non-small cell lung and pancreatic cancers. The clinical use of GEM has been limited by its rapid metabolism and short plasma half-life. These restrictions lead to frequent administration of high drug doses which can cause severe side effects. Therefore, new delivery strategies are needed aiming toward improved therapeutic effects. Single-walled carbon nanotubes (SWCNTs) are emerging as promising carriers for drug delivery due to their unique properties including high drug loading capacities, notable cell membrane penetrability and prolonged circulation times. In this work, pristine SWCNTs were functionalized through carboxylation, acylation, amination, PEGylation and finally GEM conjugation. The prepared SWCNT-GEM and SWCNT-PEG-GEM conjugates were characterized by FTIR, NMR, DSC and TEM to confirm the successful functionalization. The amount of GEM bound to the conjugates was 43.14% (w/w) for the SWCNT-GEM and 37.32% for the SWCNT-PEG-GEM, indicating high loading capacity. MTT assay on the human lung carcinoma cell line (A549) and the human pancreatic carcinoma cell line (MIA PaCa-2) demonstrated that the SWCNT-GEM was more cytotoxic than SWCNT-PEG-GEM and GEM. The SWCNT-PEG-GEM conjugates afford higher efficacy in suppressing tumor growth than SWCNT-GEM and GEM in B6 nude mice. The results demonstrate that the new formulation of GEM is useful strategy for improving the antitumor efficacy of GEM.
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PMID:In vivo drug delivery of gemcitabine with PEGylated single-walled carbon nanotubes. 2695 65

Elevated tissue inhibitor of metalloproteinase-1 (TIMP-1) is a negative prognosticator in non-small cell lung carcinoma NSCLC patients. This study sought to identify mechanisms whereby TIMP-1 impacts anticancer therapy. Using NSCLC cells and their TIMP-1 knockdown clones, we examined the chemoresistance against two chemotherapeutic agents, Gemcitabine and Cisplatin, as identified by increased apoptosis in the knockdown clones. A bead-based cytokine screening assay identified interleukin-6 (IL-6) as a key factor in chemoresistance. Exogenous human recombinant rhTIMP-1 or rhIL-6 resulted in reduced apoptosis. IL-6 expression was closely correlated with TIMP-1 kinetics and was upregulated by the addition of exogenous TIMP-1 while TIMP-1 neutralizing antibodies delayed IL-6 elevation. IL-6 production was regulated by TIMP-1, exerting its effect via activation of downstream signal transducer and activator of transcription 3 (STAT3) signaling. Both molecules and their documented transcription factors were upregulated and activated in chemoresistant NSCLC cells, confirming the roles of TIMP-1 and IL-6 in chemoresistance. To examine the role of these genes in patients, survival data from lung adenocarcinoma (LUAD) patients was curated from the cancer genome atlas (TCGA) database. Kaplan-Meier analysis found that individuals expressing low TIMP-1 and IL-6 have a higher survival rate and that the two-gene signature was more significant than the single-gene status. We define for the first time, a regulatory relationship between TIMP-1 and IL-6 in NSCLCs, suggesting that the TIMP-1/IL6 axis may be a valuable prognostic biomarker. Therapeutic interventions directed at this dual target may improve overall prognosis while negatively affecting the development of chemoresistance in NSCLC.
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PMID:TIMP-1-Mediated Chemoresistance via Induction of IL-6 in NSCLC. 3144 42


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