Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0677930 (primary tumor)
 20,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Despite the widely held belief of the resistance to chemotherapy of brain metastases, central nervous system metastases of a malignancy are equally sensitive to chemotherapy as its metastases elsewhere in the body. This is due to the fact that the blood-brain barrier is disrupted in contrast enhancing brain metastases, and does not limit the response to chemotherapy. Therefore, the response rate of the primary tumour. Up-front chemotherapeutic treatment instead of radiotherapy of brain metastases should therefore be based on the chemosensitivity of the primary tumor to the used regimen, and not on the question whether the used agent penetrates an intact blood-brain barrier. First-line chemotherapy for brain metastases or with only minor neurological signs and symptoms, and who have an indication for systematic chemotherapy for metastases elsewhere in the body. In contrast, central nervous system micrometastases may hide behind an intact barrier, and this may be clinically relevant in patients that can be cured with chemotherapy (like in small cell lung cancer). Cytochrome P450 3A4 inducing anti-epileptic drugs like phenytoin, carbamazepine and phenobarbital may significantly increase the metabolism of many chemotherapeutic agents like CPT11 and paclitaxel (but also of newer biological agents like many tyrosine kinase inhibitors). These anti-epileptic drugs should be avoided in patients requiring chemotherapy with agents metabolised through the cytochrome P450.
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PMID:The role of chemotherapy in brain metastases. 1452 68

Activation of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) results in inhibition of tumor growth in various types of cancers, but the mechanism(s) by which PPAR-gamma induces growth arrest has not been completely defined. In a recent study, we demonstrate that treatment of A549 (human non small cell lung cancer cell line) tumor-bearing SCID mice with PPAR-gamma ligands troglitazone (Tro) and pioglitazone significantly inhibits primary tumor growth. In this study, immunohistochemical analysis of Tro-treated and Pio-treated tumors with factor VIII antibody revealed a significant reduction in blood vessel density compared to tumors in control animals, suggesting inhibition of angiogenesis. Further analysis showed that treatment of A549 cells in vitro with Tro or transient transfection of A549 cells with constitutively active PPAR-gamma (VP16-PPAR-gamma) construct blocked the production of the angiogenic ELR+CXC chemokines IL-8 (CXCL8), ENA-78 (CXCL5), and Gro-alpha (CXCL1). Similarly, an inhibitor of NF-kappa B activation (PDTC) also blocked CXCL8, CXCL5, and CXCL1 production, consistent with their NF-kappa B-dependent regulation. Conditioned media from A549 cells induce human microvascular endothelial cell (HMVEC) chemotaxis. However, conditioned media from Tro-treated A549 cells induced significantly less HMVEC chemotaxis compared to untreated A549 cells. Furthermore, PPAR-gamma activation inhibited NF-kappa B transcriptional activity, as assessed by TransAM reporter gene assay. Collectively, our data suggest that PPAR-gamma ligands can inhibit tumor-associated angiogenesis by blocking the production of ELR+CXC chemokines, which is mediated through antagonizing NF-kappaB activation. These antiangiogenic effects likely contribute to the inhibition of primary tumor growth by PPAR-gamma ligands.
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PMID:PPAR-gamma activation inhibits angiogenesis by blocking ELR+CXC chemokine production in non-small cell lung cancer. 1579 29

Temozolomide (TMZ) has shown modest efficacy in the treatment of recurrent brain metastasis (BM). We designed a new regimen utilizing dose-intensified, protracted course of TMZ in combination with vinorelbine, a lipophilic large-spectrum agent, in an attempt to improve the efficacy of TMZ. This phase I study was conducted to establish the maximum tolerated dose (MTD) of vinorelbine for this combination. Patients with recurrent or progressive BM were eligible. Chemotherapy consisted of 28-day cycles with TMZ (150 mg/m2, days 1-7 and 15-21) and vinorelbine (days one and eight at escalating doses). The starting dose was 15 mg/m2, with increments of 5 mg/m2 for each cohort of 3-6 patients, until MTD was reached (30 mg/m2). A total of 21 patients were enrolled; the median age was 59 (41-77). The primary tumor was lung cancer in 13 patients (NSCLC in 10, SCLC in 3), breast in 6, renal in 1 and endometrial in 1. Vinorelbine dose was 15 mg/m2 in seven patients, 20 mg/m2 in five, 25 mg/m2 in four and 30 mg/m2 in six. Grades 3 and 4 neutropenia developed in six patients, lymphopenia in nine, and thrombocytopenia in six; other toxicities were rare. No dose-limiting toxicity was seen. Out of 18 evaluable patients 2 had a radiographic response (one partial and one minor). Disease was stable in 6 of 18 patients and the median survival was 27 weeks. This regimen was well tolerated and a phase II trial using a dose of 30 mg/m2 of vinorelbine is warranted.
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PMID:Vinorelbine combined with a protracted course of temozolomide for recurrent brain metastases: a phase I trial. 1661 43

The relationship between cancer and coagulopathy was suggested by Trousseau nearly 150 years ago. Later, it became more evident that oncologic patients are at a higher risk of experiencing thromboembolic events. This can be due to activation of the coagulation system either by neoplastic cells or by prescribed therapies (chemotherapy or surgical procedures). In fact, these events can constitute the first manifestation of cancer, and their recurrence, despite efficient anticoagulation, has been described. The coagulation system is normally activated in order to provide healing. In the presence of neoplasms, this complex system is activated as a response to multiple stimuli and seems to contribute to cancer progression. Activation of the coagulation system has a greater effect on metastatic foci than on the primary tumor. However, most cancer victims die from complications caused by metastasis, which underscores the importance of this theme. In this area, various mechanisms have been described, creating promising perspectives for future treatments. The current success in using low-molecular-weight heparins against small cell lung cancer is encouraging. Although the knowledge of those mechanisms is relatively incipient, many basic research and clinical studies are underway.
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PMID:Hypercoagulability and lung cancer. 1854 28

Only 20-30% of patients with non small cell lung cancer (NSCLC) present with early-stage disease at the time of diagnosis and may benefit by surgical resection. Five-year survival in early-stage disease varies from 38 to 57% for stage IB and from 13 to 23% for stage IIIA according to the clinical and pathological assessment of the patients. Occult micrometastatic disease already present in many patients with resectable NSCLC at the time of diagnosis and surgical treatment leads to local and distant disease recurrence. Therefore a more systemic approach should be considered in early-stage disease. The role of adjuvant chemotherapy has already been established in this field. Within the past decade attention has been focused on the possible beneficial effects of preoperative chemotherapy considering that patients' compliance to the induction treatment can be very high with eventual eradication of micrometastatic disease and primary tumor downstaging. In this review we present the currently available data on induction chemotherapy followed by surgery in early-stage (stages IB-IIIA) NSCLC with a fundamental question to be answered: is this approach justified in current clinical practice?
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PMID:Preoperative chemotherapy in early-stage (stage IB-IIIA) resectable non small cell lung cancer. Is it justified? 1855 60

Lung cancer in women is increasing in worldwide. This process beginning with the difference on the susceptibility of lung cancer in women smokers may be different from men in the prognosis. In this study, it was aimed to evaluate the clinical features, and prognostic factors of female patients with lung cancer diagnosed between January 2000-December 2005. The data of 109 patients data was evaluated. The mean age was 59.40 +/- 11.56 and 17 (15.6%) patients were smokers. In 20 patients (18.3%) having a family history of cancer, 55% of them had a relative with lung cancer. In admission, cough (81.7%), dyspnea (78.9%), chest pain (40.3%) were the most frequent presenting symptoms. The most common site of tumoral lesion in bronchoscopy were right upper lobe (16.5%). In the study group histopathological diagnosis were as follows; adenocarcinoma (44.9%), small cell lung cancer (SCLC) (19.3%), squamous cell (10.1%), non-small cell lung cancer (NSCLC) --undefined (22.0%), carsinoid tumors (2.8%), in non-smokers adenocarcinoma was significantly higher than smokers (44.9%/17.7%) (p< 0.001). 61.9% of NSCLC patients and 57.1% of SCLC patients had a stage IV disease at the initial evaluation. The most common sites of metastasis were bone (28.4%), liver (22.9%), and brain (11.9%), there were multiple metastasis in 10 patients. Median survival time was found as 288 days. In univariate analysis, comorbidity, primary tumor stage, bone metastasis, advanced disease stage, ECOG performance score >or= 2 and supportive care alone were poor prognostic factors. In multivariate analysis, poor performance status (p= 0.003), advanced disease stage (p= 0.002) and bone metastasis (p= 0.04) were negatively related to survival. In women, the definition of the clinical features, disease course and survival related factors may contribute to our future treatment approaches based on our national data.
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PMID:[Lung cancer in women: clinical features and factors related to survival]. 1893 27

Small cell lung cancer constitutes 15-20% cases of lung cancers, currently the leading cause of death from malignant diseases. It also causes the demise of >90% of affected individuals in 5 years. We have established a new SCLC cell line STP54 derived from fine needle aspirate of metastatic supraclavicular lymph node of 54 -year-old women for model experiments. The primary tumor was diagnosed by histopathological examination as combined type of small cell lung cancer with a non-small cell component. We cultured the cancer cells in the RPMI 1640 medium. In the long-term culture only the small cell component survived. The cell line was established after 30 passages and then characterized by performing cell morphology, cell growth analysis, tumorigenicity in vitro and flow cytometry analysis of selected markers (like NCAM, cytokeratines, HLA-ABC, Fas, Bcl-2, p53, CXCR4, CD210). The cells were growing in floating aggregates and show features suggesting its invasiveness. We suggest that this new cell line may serve as a valuable tool for further studies on lung tumor biology, molecular pathogenesis and metastatic mechanism.
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PMID:Characterization of a new small cell lung cancer (SCLC) cell line STP54 derived from a metastatic bioptate of a combined type of SCLC with Non-SCLC component. 1941 48

Small cell carcinomas are most frequently localised within the lung, however, they also may be detected at extrapulmonary sites such as the gastrointestinal tract and the genitourinary tract. The confirmation of a small cell carcinoma outside of the lung may not necessarily indicate the presence of a metastasis, however, it also may represent the primary tumor itself. We present the case of a patient with a small cell carcinoma of the lung with metastases to the stomach. A regression of the primary lung tumor and the disappearance of the gastric metastases could be achieved by chemotherapeutic treatment with carboplatin, etoposide, and vincristine. However, death due to pneumonia occurred 3 months after initial diagnosis. This case illustrates that in rare cases a metastasis from small cell lung cancer may occur in the intestinal tract even without leading to distinctive symptoms.
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PMID:[Gastric metastasis from small cell lung cancer]. 1970 8

We report a 59-year-old man who developed dysesthesia in all extremities with severe loss of deep sensation over three months. A radiating radicular pain was also noted in the extremities. The nerve conduction study barely elicited sensory nerve action potentials both in the median and in the sural nerve. An extensive search for anti-neuronal antibodies including anti-Hu and anti-CV2 antibody was negetive. The biopsy specimen of an enlarged tracheobronchial lymph node revealed squamous cell carcinoma. The subsequent chemotherapy and radiation therapy for the neoplasm improved the radicular pain and the deep sensation to a moderate extent, leading to the diagnosis of paraneoplastic subacute sensory neuropathy (SSN). In general, cases with paraneoplastic SSN are associated mostly with small cell lung cancer, and quite rarely with squamous cell lung cancer. The early detection and the treatment of the primary tumor are crucial in a patient with subacute progression of sensory-dominant neuropathy.
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PMID:[Subacute sensory neuronopathy associated with squamous cell carcinoma of the lung: a case report]. 1982 1

Small cell carcinoma (SCC) is commonly of pulmonary origin. Pleural small cell carcinoma is a very uncommon feature. We report here a case of small cell carcinoma of the pleura in a 36 year old man. The diagnosis of primary disease SCC of the pleura was established by transparietal pleural biopsy in absence of any mediastino-pulmonary or extrathoracic other lesions that could be the primary tumor. The treatment was based on chemotherapy with cisplatin and etoposide. The patient died four months in spite of cytotoxic chemotherapy. Extrapulmonary small cell carcinoma is a rare entity. Immunohistochemistry study is very useful for the diagnosis. The prognosis seems to be worse than the small cell lung cancer.
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PMID:[A new case of pleural small cell carcinoma]. 1999 55


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