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)

Hypercalcemia may be a manifestation of a variety of disorders including hyperparathyroidism, hypervitaminosis D, sarcoidosis, multiple myeloma, hyperthyroidism, acute osteoporosis, metastatic bone disease, and a number of primary malignancies. Hypercalcemia may be seen in as many as 1.5% of all patients with malignant disease, with or without bony metastases. The neoplasms most commonly associated with hypercalcemia include carcinoma of the lung (all cell types), breast cancer, squamous cell carcinomas, hematologic malignancies, and renal cell carcinoma. Observation of a number of instances of hypercalcemia attendant on urologic malignancies prompts the brief report of 4 characteristic cases with documentation of response to therapy. Management of severe and debilitating hypercalcemia is emphasized. Urologists should be aware of new agents available for such treatment.
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PMID:Hypercalcemia and urologic malignancies. 781 68

Sweet's syndrome is a rare dermatosis characterized by fever, neutrophilia, raised painful erythematous plaques and a dense dermal infiltrate consisting of mature neutrophils. About 15% of published cases occurs in association with hematologic malignancies, so that the syndrome is considered a paraneoplastic phenomenon; conversely, the association with solid tumors is very rare (up to now seven cases). We report the first case of Sweet's syndrome associated with adenocarcinoma of the lung. The syndrome appeared when the tumor was in remission after five courses of chemotherapy, and remained the only sign of underlying malignancy for 2 months, when lung cancer relapsed.
Lung Cancer 1993 Oct
PMID:Sweet's syndrome and malignancy: report of the first case associated with adenocarcinoma of the lung. 806 9

Recently an increase of the elderly patients with hematological malignancies has been pointed out. We analyzed second malignancies in elderly patients with hematological malignancies (95 age 65 or more), and made a comparative study with non-elderly case for the past 5 years. Second malignancies were observed in 26 cases out of the total of 282 hematological malignancies (9.2%). The percentage of patients with second malignancies in the elderly group (19/95; 20%) was significantly higher than that of the non-elderly group (7/187; 3.7%). Among the all kinds of hematological malignancies, the second malignancies were mainly observed in cases with myelodysplastic syndrome and chronic myelo-proliferative disorder. Colon carcinoma, gastric carcinoma and lung carcinoma accounted for nearly half of all the second malignancies. On 11 of the 26 cases with second malignancies, the first malignancies had been treated with some anti-cancer drug such as alkylating agents. Development of a second cancer was greater in cases in which the first hematological malignancy was treated with alkylating agents more than in cases in which the first carcinoma was not treated with alkylating agents.
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PMID:[Elderly cases of hematological malignancies with second malignancies]. 823 Jul 94

Topotecan (Hycamtin) is a promising new topoisomerase I-targeting anticancer agent that first entered clinical trials in 1989 under National Cancer Institute sponsorship in collaboration with SmithKline Beecham. In 1996, it was approved for use by the United States Food and Drug Administration (FDA) for previously treated patients with advanced ovarian cancer. For these patients, topotecan provides another therapeutic option upon disease progression after initial platinum-based chemotherapy. Topotecan also has activity in other tumor types, including small-cell lung cancer, hematologic malignancies and pediatric neuroblastoma and rhabdomyosarcoma. Topotecan combination regimens with paclitaxel (Taxol), etoposide (VePesid), cisplatin (Platinol), and cytarabine and with other treatment modalities, such as radiation therapy, are in development. Studies evaluating topotecan combinations as initial treatment in such diseases as ovarian and small-cell lung carcinoma are also underway. It is hoped that earlier use of topotecan, with its novel mechanism of action, will prolong survival and increase cure rates in patients with these chemoresponsive tumors. Whether or not such hopes are realized, these important studies will help define the role of topotecan in cancer chemotherapy.
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PMID:Clinical status and optimal use of topotecan. 939 64

Several tumor markers have been evaluated in pleural fluid, but their clinical role has not been firmly established. The aim of this study is to determine the diagnostic value of carbohydrate antigen 549 (CA 549) levels in pleural fluid, and to compare it with another previously studied tumor markers: carcinoembryonic antigen (CEA), CA 15.3 and CA 72.4. We prospectively studied 252 patients with pleural effusion: 101 malignant (20 mesothelioma) and 151 of several benign diseases. The levels of the tumor markers were measured by immunoradiometric assays (RIA). CA 549 in pleural fluid has an acceptable sensitivity (0.49), with high specificity (0.99). The best combination of tumor markers for differentiating malignant from benign effusions was CA 549+CEA+CA 15.3, with a sensitivity of 0.65, specificity of 0.99 and accuracy of 0.85. The addition of any one tumor marker assay consistently improved the diagnostic value of cytology. In our study, none of the tumor markers was organ-specific. When mesothelioma and hematological malignancy were ruled-out, the combination of CA 549+CEA+CA 15.3, improved the results up to a sensitivity of 0.77, specificity of 1 and accuracy of 0.92. In conclusion, CA 549 assay has an acceptable sensitivity with high specificity. The best combination of tumor markers in this series with a high relative frequency of mesothelioma and low frequency of breast carcinoma was CA 549+CEA+CA 15.3. Individual tumor markers or their combination increased the sensitivity of pleural cytology.
Lung Cancer 2003 Jun
PMID:Diagnostic value of CA 549 in pleural fluid. Comparison with CEA, CA 15.3 and CA 72.4. 1278 27

Bcl-2 protein plays a critical role in inhibiting anticancer drug-induced apoptosis, which is mediated by a mitochondria-dependent pathway that controls the release of cytochrome c from mitochondria through anion channels. Constitutive overexpression of Bcl-2 or unchanged expression after treatment with anticancer drugs confers drug resistance not only to hematologic malignancies but also to solid tumors. The down-regulation of Bcl-2 protein by the antisense (AS) Bcl-2 (oblimesen sodium) may be a useful method for targeting the antiapoptotic protein and thereby increasing the chemotherapeutic effect of anticancer drugs. Several randomized, controlled, Phase III trials have compared standard chemotherapy with a combination of AS Bcl-2 and standard chemotherapy for the treatment of patients with chronic lymphocytic leukemia, multiple myeloma, malignant melanoma, and nonsmall cell lung carcinoma. Nonrandomized clinical trials and preclinical evaluations of AS Bcl-2 also are underway for patients with other malignancies. Here, the authors review the current clinical and preclinical evaluations of AS Bcl-2 and discuss its potential to act as a chemosensitizer and to enhance the therapeutic effect of cancer chemotherapy.
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PMID:Therapeutic potential of antisense Bcl-2 as a chemosensitizer for cancer therapy. 1550 11

The proteasome is responsible for the degradation of intracellular proteins, including several involved in cell cycle control and the regulation of apoptosis. Preclinical studies have shown that the proteasome inhibitor bortezomib decreases proliferation, induces apoptosis, enhances the activity of chemotherapy and radiation, and reverses chemoresistance in a variety of hematologic and solid malignancy models in vitro and in vivo. Proteasome inhibition with bortezomib has specifically promoted apoptosis of tumor cells through the stabilization of p53, p21, p27, Bax, and IkappaBalpha, resulting in nuclear factor kappaB inhibition. Bortezomib was the first proteasome inhibitor to enter clinical trials. In two Phase II trials, SUMMIT and CREST, it was found that treatment with bortezomib, alone or in combination with dexamethasone, produced durable responses with meaningful survival benefits in patients with recurrent and/or refractory multiple myeloma. In the APEX Phase III trial, bortezomib produced significant survival benefits and improved response rates over high-dose dexamethasone at first recurrence and beyond in patients with multiple myeloma. Clinical trials evaluating the safety and activity of bortezomib alone or in combination regimens with dexamethasone, doxorubicin, melphalan, prednisone, and/or thalidomide in the treatment of patients with newly diagnosed multiple myeloma have shown encouraging results. Preliminary studies suggest that bortezomib may serve as induction therapy before stem cell transplantation. Proteasome inhibition with bortezomib also has shown activity with manageable toxicity in mantle cell and other lymphomas, leukemias, and solid malignancies, including nonsmall cell lung carcinoma. Further studies with bortezomib as monotherapy and in combination regimens in the treatment of solid and hematologic malignancies are warranted.
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PMID:Proteasome inhibition and its clinical prospects in the treatment of hematologic and solid malignancies. 1617 3

Non-small-cell lung cancer (NSCLC) represents approximately 80% of all lung cancers. With modern platinum- based combination regimens, overall median survival has reached 9-12 months. Antifolates are active against several solid tumors and hematologic malignancies. The cytotoxic action of antifolates is mainly related to their ability to inhibit several different folate-dependent enzymes involved in DNA synthesis. Pemetrexed is a novel multitargeted antifolate that inhibits at least 3 of the enzymes involved in purine and pyrimidine synthesis: thymidylate synthase (TS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT). Pemetrexed was approved for the treatment of relapsed NSCLC as it produced equivalent response and survival rates and less toxicity compared with docetaxel. Pemetrexed in combination with platinum analogues or with gemcitabine showed equivalent clinical impact compared with standard combinations of platinum plus third-generation agents. We analyze the potential implications of pemetrexed's role in first-line chemotherapy of NSCLC as well as hints of differential cytotoxic action according to histology, new schedules of vitamin supplementation, and target enzymes expression levels. Issues of pharmacogenomics are becoming relevant in defining pemetrexed efficacy. Chemosensitivity was significantly linked to low levels of TS, GARFT, and DHFR in preclinical models. Consequently, the differential expression of TS according to histology might explain the different activity of pemetrexed according to histology, as recently postulated.
Clin Lung Cancer 2008
PMID:New data integrating multitargeted antifolates into treatment of first-line and relapsed non-small-cell lung cancer. 1941 26

Skin is an uncommon site for metastasis. This study was done to evaluate the role of FNAC as an important tool for investigating cutaneous and subcutaneous nodules in patients with known malignancy or as a primary manifestation of an unknown malignancy. All the FNAC done from January 2003 to August 2008 were reviewed (n = 55,556). Ninty-five patients (49 males and 46 females with age range of 4-96 years) with cutaneous/subcutaneous nodules which were diagnosed as metastasis were analyzed. Primary tumors of skin/subcutis were excluded from the study. In our study, 63 out of 95 cases had a known primary malignancy. Of these, five had underlying hematological malignancy and 58 patients had solid organ tumors. Lung carcinoma was seen to metastasize most commonly to skin in males and breast carcinoma in females. The most common site for a cutaneous/subcutaneous metastasis was chest wall [40 followed by abdominal wall (14) and scalp (9)]. Multiple site involvement was also observed (8). In 32 cases primary site was not known. They were most commonly diagnosed as poorly differentiated carcinoma followed by adenocarcinoma. FNAC can diagnose a variety of tumors in the skin and support the diagnosis of a metastasis in case of a known primary and offer a clue to underlying malignancy in case of an occult primary.
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PMID:Role of fine-needle aspiration cytology in evaluation of cutaneous metastases. 1953 99

Constitutive activation of STAT3 is a common feature in many solid tumors including non-small cell lung carcinoma (NSCLC). While activation of STAT3 is commonly achieved by somatic mutations to JAK2 in hematologic malignancies, similar mutations are not often found in solid tumors. Previous work has instead suggested that STAT3 activation in solid tumors is more commonly induced by hyperactive growth factor receptors or autocrine cytokine signaling. The interplay between STAT3 activation and other well-characterized oncogenic "driver" mutations in NSCLC has not been fully characterized, though constitutive STAT3 activation has been proposed to play an important role in resistance to various small-molecule therapies that target these oncogenes. In this study we demonstrate that STAT3 is constitutively activated in human NSCLC samples and in a variety of NSCLC lines independent of activating KRAS or tyrosine kinase mutations. We further show that genetic or pharmacologic inhibition of the gp130/JAK2 signaling pathway disrupts activation of STAT3. Interestingly, treatment of NSCLC cells with the JAK1/2 inhibitor ruxolitinib has no effect on cell proliferation and viability in two-dimensional culture, but inhibits growth in soft agar and xenograft assays. These data demonstrate that JAK2/STAT3 signaling operates independent of known driver mutations in NSCLC and plays critical roles in tumor cell behavior that may not be effectively inhibited by drugs that selectively target these driver mutations.
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PMID:STAT3 is activated by JAK2 independent of key oncogenic driver mutations in non-small cell lung carcinoma. 2231 90


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