Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0007097 (carcinoma)
 152,788 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We examined the apoptosis of tongue carcinoma cells and the effects of anticancer drugs to identify the molecules that mediate apoptotic cascade in the malignancy. Carboplatin (CBDCA) induced apoptosis of SCC-9 and SCC-25, human well-differentiated tongue squamous carcinoma cell lines. Neutralizing anti-Fas (APO-1/CD95) and anti-Fas ligand (FasL) antibodies obliterated the CBDCA-induced cell death. In the absence of CBDCA, cytotoxic anti-Fas antibody, which binds to and activates Fas at the cell surface, failed to induce apoptosis. However, in the presence of CBDCA, the cytotoxic antibody markedly enhanced the apoptosis in a dose-dependent manner. Western blotting and reverse-transcription (RT) PCR revealed that there were no alterations in Fas or FasL expression upon CBDCA treatment. SCC-25 induced apoptosis of Jurkat cells, Fas-sensitive T-lymphatic leukemia cell line, and the apoptosis was inhibited by neutralizing anti-Fas or anti-FasL antibody. These results indicate that the tongue carcinoma cells express nonfunctional Fas and functional FasL, which by themselves fail to induce apoptosis. The expression of FADD in the tongue carcinoma cells was very low and was largely enhanced by CBDCA treatment. Suppression of FADD expression using the specific antisense oligonucleotide resulted in a failure of CBDCA induction of cell death. These results indicate that a deficiency of FADD is involved in the insensitivity of tongue carcinoma cells for Fas activation, and that CBDCA treatment switches nonfunctional Fas to functional Fas by upregulation of FADD expression, resulting in activation of a Fas-sensitive pathway leading to apoptosis.
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PMID:Carboplatin induces Fas (APO-1/CD95)-dependent apoptosis of human tongue carcinoma cells: sensitization for apoptosis by upregulation of FADD expression. 1274 Sep 5

The refinement of radiation therapy techniques should result in a decrease in morbidity in canine and feline nasal carcinoma patients and should further allow for the addition of adjuvant therapies. Patients with large oral tumors that are incompletely excised should have radiation therapy added to their treatment regimen. Tumors with significant metastatic potential, such as melanoma, should be considered for addition of chemotherapy. Carboplatin has activity in melanomas and is being added at several institutions, but trial results are not yet available. Chemoradiation has become the treatment of choice for human head and neck squamous cell carcinomas but remains largely unexplored in veterinary medicine. Hopefully, development of chemoradiation will benefit feline squamous cell carcinoma patients, because current treatment regimens are largely ineffective. Immunotherapy agents and targeted biologic therapeutics seem to hold promise for the future.
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PMID:Multimodality therapy for head and neck cancer. 1285 39

Human tumor cells lines with acquired resistance to cisplatin (DDP) and carboplatin (CBDCA) are often cross-resistant to copper and vice versa, and some DDP-resistant cells overexpress the copper export pump ATP7B. We sought to demonstrate that ATP7B directly mediates resistance to DDP and CBDCA by stably transfecting human carcinoma cells with a vector designed to express ATP7B. Increased expression of ATP7B rendered all three cell lines tested more resistant to a 1-h exposure to DDP (1.6-2.6-fold), CBDCA (1.5-1.6-fold), and copper (1.2-1.4-fold). The effect of ATP7B on the cellular pharmacology of 64Cu and [14C]CBDCA was investigated in more detail using one cell pair (2008 cells transfected with an empty vector or an ATP7B-expressing vector). In the 2008/ATP7B subline, steady-state copper levels were decreased under both basal and copper-supplemented conditions, as was steady-state CBDCA content upon exposure to 50 microM [14C]CBDCA. Over the first 5 min, the average rate of accumulation of copper and CBCDA in the 2008/ATP7B cells was reduced by 37 and 61%, respectively. Efflux was more rapid from 2008/ATP7B cells for both copper and CBDCA. Two-compartment modeling indicated that the second phase of efflux was increased by a factor of 3.9-fold for CBCDA and to an even greater extent for copper. We conclude that expression of ATP7B regulates sensitivity to CBDCA as well as to DDP and copper and that a transporter that normally mediates copper homeostasis modulates the cellular pharmacology of CBDCA.
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PMID:The copper export pump ATP7B modulates the cellular pharmacology of carboplatin in ovarian carcinoma cells. 1286 52

Ifosfamide (IFO) has demonstrated activity in recurrent/metastatic squamous cell head and neck carcinoma with an overall response rate of 24-26%. Better results are reported for chemotherapy-naive patients; in heavily pretreated cases results are poor and toxicity unacceptable. Cisplatin-IFO combination in stage III-IV is probably more active than IFO alone (ORR = 60-72 vs. 50%) but is indicated in patients who desire aggressive treatment and are physically able to tolerate the drugs. The carboplatin-IFO scheme is better tolerated than the cisplatin-IFO regimen with superimposable clinical results (ORR = 69%; CR = 15%). Carboplatin-taxol-IFO is one of the most active regimens in recurrent (ORR = 59%; CR = 17%) and in locally advanced (ORR = 81%; CR = 31%) head and neck cancer. Its role in the multidisciplinary treatment of advanced head and neck cancer is under investigation. In recurrent/metastatic undifferentiated nasopharygeal carcinoma, IFO combinations have proven to be effective as first- and second-line treatment.
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PMID:Ifosfamide in the treatment of head and neck cancer. 1458 45

AP5280 is a novel N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-bound platinum (Pt) therapeutic designed to increase the therapeutic index relative to conventional, small-molecule platinum agents. The platinum-polymer construct accumulates in solid tumours on the basis of increased capillary permeability. The bound platinum moiety is present as an N,O-Pt chelate at the distal end of a tetrapeptide linker, glycine-phenylalanine-leucine-glycine, and the weight-average molecular weight (Mw) of the construct is 22 kDa. The antitumour activity and toxicity of AP5280 were assessed in the syngeneic murine B16F10 and Lewis lung tumour models, and in the human ovarian carcinoma 2008 and head and neck squamous carcinoma UMSCC10b xenograft models. The maximum tolerated dose (MTD) of AP5280 was 6-fold greater than that of carboplatin (CBDCA) in vivo. AP5280 was active in all four tumour models, and it displayed a higher therapeutic index than CBDCA in each of these tumour models. The antitumour effect of AP5280 given at 16% of its MTD was equivalent to that produced by a MTD of CBDCA. Thus, consistent with the design goal for this drug, and despite being less potent than CBDCA, AP5280 produced less systemic toxicity relative to its antitumour activity and thus has a greater therapeutic index. On the basis of the improved therapeutic index evidenced in these models, AP5280 has been advanced into clinical trials.
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PMID:Improved targeting of platinum chemotherapeutics. the antitumour activity of the HPMA copolymer platinum agent AP5280 in murine tumour models. 1472 45

We report a case of hypopharyngeal carcinoma with recurrent neck metastasis. Preoperative chemoradiation and pharyngo-laryngo-esophagectomy with bilateral neck dissection was done as first-line therapy. Six months later, the carcinoma metastasized to the right paratracheal lymph node. Because of resistance to chemoradiation (CBDCA) as second-line therapy, we administered TS-1 for the treatment after 60 Gy radiation. The chemotherapy with TS-1 resulted in complete response by diagnostic imaging (CT). There was no sign of recurrence for 1 year after 5 courses of treatment. TS-1, which allows oral chemotherapy on an outpatient basis, would be a useful drug for treatment with radiotherapy in patients with advanced and/or recurrent head and neck cancer.
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PMID:[A case of neck metastasis from hypopharyngeal carcinoma successfully treated with TS-1]. 1511 15

A 57-year-old female underwent left lower lung lobectomy and was histologically diagnosed as having lymphoepithelioma-like carcinoma. One year and 2 months after surgery, pleural thickening was recognized, so she was administered 4 courses of CBDCA/PTX combined chemotherapy. Toxicity associated with the chemotherapy was very mild. Pleural thickening and effusion disappeared after treatment, so this case was judged to be a complete response. She suffered from left chest pain before chemotherapy, which later lessened. She was thus able to stop taking NSAIDs. Because primary pulmonary lymphoepithelioma-like carcinoma is a rare tumor, there is no standard chemotherapy treatment. CBDCA/PTX combined chemotherapy is effective for pulmonary lymphoepithelioma-like carcinoma and shows good tolerability and improves QOL.
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PMID:[A case of recurrent pulmonary lymphoepithelioma-like carcinoma responding to treatment with CBDCA/paclitaxel combined chemotherapy]. 1533 46

The human tongue well-differentiated squamous carcinoma cell line, SCC-25, shows Fas-dependent apoptosis by treatment with carboplatin (CBDCA). FADD is markedly up-regulated by CBDCA, resulting in the induction of apoptosis. FAP-1, antiapoptotic tyrosine phosphatase, is expressed in the cytosol and blocks the transduction of the "death signal" from Fas to downstream. In this study, we show that etodolac, a selective cyclo-oxygenase-2 inhibitor, enhanced CBDCA-induced apoptosis of SCC-25, although etodolac alone did not induce the apoptosis. In combination with CBDCA, etodolac significantly decreased FAP-1 expression both at protein and mRNA levels, although etodolac by itself did not inhibit FAP-1 expression. These results indicate that etodolac, when combined with CBDCA, can enhance an action of anticancer drug through the suppression of FAP-1 expression.
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PMID:Etodolac, a selective cyclo-oxygenase-2 inhibitor, enhances carboplatin-induced apoptosis of human tongue carcinoma cells by down-regulation of FAP-1 expression. 1559 89

A 19-year-old man visited our hospital complaining of dyspnea. Chest X-ray and computed tomography (CT) showed a huge mass in the right anterior mediastinum. We diagnosed this as invasive thymoma by microscopic examination of specimens obtained by echo-guided needle biopsy. The patient underwent 6 courses chemotherapy [1st course : carboplatin (CBDCA) + doxorubicin hydrochloride (DXR) + vincristine sulfate (VCR) + cyclophosphamide (CPA), 2nd, 3rd-6th course : cisplatin (CDDP) + ADM + VCR + CPA]. At achievement of partial response (the reduction rate of the tumor size : 91.4%), the tumor was completely resected. The pathological examination of the resected specimens yielded a diagnosis of large cell carcinoma. Preoperative chemotherapy with ADOC regimen may be effective in advanced thymic carcinoma.
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PMID:[Complete resection for giant thymic carcinoma after simultaneous combination chemotherapy]. 1582 54

A 40-year-old man suffering from right cheek swelling was first diagnosed with ameloblastoma or anaplastic poorly-differentiated carcinoma of the head and neck region. He received 2 courses of CDDP/TXT chemotherapy (cisplatin 75 mg/m2, docetaxel 80 mg/m2) and achieved a partial response, but his carcinoma of the pancreas recurred. He also achieved a partial response with 2 courses of CBDCA/TXL regimen (carboplatin AUC=6, paclitaxel 200 mg/m2), but later died from his progressive disease. The autopsy revealed a pathological diagnosis of metastatic endocrine carcinoma of the pancreas. This case was close to a cancer with an unknown primary (CUP) site, and several favorable sub-sets of CUP have been identified, which are responsive to systemic chemotherapy. Poorly-differentiated neuroendocrine carcinomas like this case are highly sensitive to chemotherapy, and a careful pathological diagnosis may clarify its sensitivity to chemotherapy and the prognosis.
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PMID:[An autopsied case of metastatic endocrine carcinoma of the pancreas with primary site difficult to identify]. 1591 70


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