Molecular characterization as a target for cancer therapy in relation to orphan status disorders (Review)

The long-term effort in investigating chemical methods to eliminate only cancer cells has improved our knowledge and has led to the development of new drugs. The targets for cancer treatment may be large polymeric molecules such as DNA or microtubules as well as regulatory pathways for tumor development and cell survival preservation or tyrosine kinase activity. Examples of new agents are: trastuzumab (Herceptin), a humanized monoclonal antibody that blocks the HER-2/neu proto-oncogene in combination with cytotoxic agents, is used in a percentage of breast cancer patients; signal transduction inhibitor of abl tyrosine kinase STI 571 (Glivec) has been shown to be an active treatment for chronic myeloid leukemia and GISTs; epidermal growth factor receptors in certain tumors have been targeted with agents such as C225 (Cetuximab) and ZD 1839 (IRESSA); an adenosine deaminase analogue of deoxyadenosine, Cladribine (2-chloro-2 deoxy-adenosine) has shown high effectiveness in hairy-cell leukemia and the multitargeted antifolate (Premetrexed) and several vaccines have been studied and are in clinical trials for resistant cancers. These new drug developments represent a promising field for future cancer management

Plasma VEGF levels in breast cancer patients with and without metastases

Vascular endothelial growth factor (VEGF) is a key mediator of angiogenesis since it stimulates the formation of new blood vessels. Basic fbroblast growth factor (bFGF) is related to the promotion of endothelial cells into tube-like structures, and it is therefore expected to promote angiogenesis with a greater potency than VEGF. VEGF and bFGF are considered to be biomarkers that predict treatment effectiveness. Elevated plasma VEGF and bFGF levels have been reported in a variety of different malignant tumors, and patients with metastatic disease have also been reported to present with higher serum VEGF and bFGF levels. Other studies have documented controversial results with respect to the prognostic and predictive value of the aforementioned biomarkers. This study aimed to determine the plasma VEGF and bFGF levels in breast cancer patients without metastatic disease compared with breast cancer patients with advanced metastatic disease. The study included 93 patients with breast cancer, 46 without recurrent disease (group A) and 47 with metastatic disease (group B), as well as 21 healthy individuals. The median age was 58 years (range 34-78) for group A and 59 years (range 37-75) for group B. All 93 patients underwent chemotherapy, adjuvant for group A, and adjuvant plus chemotherapy for group B patients with advanced disease. Plasma VEGF and bFGF levels were determined using a quantitative sandwich immunoassay, and samples were tested in triplicate (ELISA). The plasma levels of VEGF and bFGF varied greatly, i.e., from extremely low to extremely high in the two groups, as well as in the healthy individuals. No statistically signifcant difference was found between the two groups or between the patients and healthy individuals. Data of the present study therefore showed that VEGF and bFGF levels are not valuable biomarkers for predicting treatment outcome

Paclitaxel and carboplatin in pretreated advanced gastric cancer: A phase II study

In the present study, the combination of paclitaxel and carboplatin was applied in the treatment of gastric carcinoma. This cytotoxic combination has been an effective regimen with acceptable toxicity in ovarian, lung and head and neck cancers. We evaluated 47 patients (37 male, 10 female), all with advanced disease and all having undergone prior chemotherapy treatment. All patients had disease progression or no response to the prior treatment. Forty-four patients had undergone a previous gastrectomy for gastric adenocarcinoma and 3 patients were inoperable at diagnosis. Paclitaxel 175 mg/m2 was administered as a three-hour infusion, followed by carboplatin 5 AUC infused for 90 min. Thirteen (27.66%) patients showed partial response with a median survival of 10 months; 3 (6.38%) patients showed minor response and 13 patients, stable disease with clinical benefit. The median survival of patients with minor response and disease stability was 6 months. Eighteen (38.29%) patients had disease progression with a median survival of 3 months. It appears that in advanced cancer patients, the paclitaxel-carboplatin combination is an effective second-line treatment, resulting in partial response and disease stability in 61% of patients as well as in a prolongation of median survival

Paclitaxel combined with cis-platin as second-line treatment in patients with advanced non-small cell lung cancers refractory to cis-platin.

We combined paclitaxel with cis-platin as second-line treatment in patients with non-small cell lung cancer (NSCLC) who had previously undergone first-line therapy with cis-platin combined with cytotoxic drugs other than taxanes. The aim was to evaluate the effect of this cytotoxic combination in patients with refractory tumour to cis-platin. All 36 patients in the study population were evaluable for toxicity and 35 for response. Nine patients were stage IIIa, 15 IIIb and 12 IV. Prior treatment involved cis-platin plus vindesine and epirubicin or vinblastine and mitomycin-C; second-line treatment involved cis-platin (90 mg/m2) and paclitaxel (175 mg/m2), administered once every 3 weeks with 2-6 courses per patient. Partial response (40%) was obtained in 14 patients, 8 of whom had achieved minor response or stable disease after first-line treatment. Response duration was a minimum of 3 months. Toxicity was tolerable; only neurotoxicity was grade II in 16.7% of the patients. On the basis of our results, paclitaxel can be recommended as a very effective cytotoxic drug for NSCLC patients

Tamoxifen in Carcinoid Syndrome

To the Editor: Attempts to control carcinoid syndrome with chemotherapy have produced partial and temporary responses in some patients.1 Streptozocin is probably the drug of choice, but fluorouracil, doxorubicin, cyclophosphamide, mitomycin, dactinomycin, methotrexate, and nitrosoureas have also been used as single agents or in combination. Inhibition of serotonin synthesis by enzymatic inhibitors of 5-hydroxytryptophan decarboxylase2 or of hydroxylation of tryptophan3 has also been tried. Treatment with p-chlorophenylalanine, a potent depletor of tissue serotonin,4 has reduced the gastrointestinal symptoms. Serotonin antagonists are effective enough to reduce gastrointestinal symptoms, although they are not harmless and should be used with caution. We.  . . No extract is available for articles shorter than 400 words. © 1981, Massachusetts Medical Society. All rights reserved

Granulocyte colony-stimulating factor expression as a prognostic biomarker in non-small cell lung cancer

Hematologic paraneoplastic alternations may not be very common, but they have been observed in a small number of patients. Granulocytosis has been described in several malignancies and its common mechanism may be associated with granulocyte colony-stimulating factor (G-CSF) production by the tumor. High neutrophilia (150,000-240,000 white blood cell count) observed in two patients with non-small cell lung cancer led us to run the present trial. The purpose of this study was to compare the white blood cell counts and the G-CSF plasma levels of the patients and classify the results into groups, as well as to determine the survival rates of the patients in each of the groups. The histological specimens and plasma of two patients as well as the plasma of another 87 patients with several malignancies, were examined. The plasma G-CSF levels were determined using a quantitative sandwich immunoassay technique (Quantikine; RYSD Systems) according to the manufacturer's instructions and all samples were tested in triplicate. It was found that 12 patients had a white blood cell count increased beyond normal as well as a high G-CSF plasma level and the survival of these patients was shorter as compared to the rest of the patients. We assume that these findings may indicate that increased G-CSF levels may function as a biomarker of survival. Copyright © 2011 Spandidos Publications Ltd. All rights reserved

Pleural effusion and pulmonary injury as an unusual complication to chemotherapy in non-small cell lung cancer patients

We report the appearance of pleural effusion, or pulmonary failure after chemotherapy, followed by tumor reduction, in a small number of patients. Five hundred and fifty-four patients with lung cancer have undergone chemotherapy at our Institute during the last ten years. Three patients with non-small cell lung cancer (NSCLC), with locally advanced disease, exhibited an unusual consequence following cytotoxic drug treatment. Two patients with NSCLC had pleural effusion which improved within 2-3 weeks, together with tumor reduction, which allowed the continuation of treatment. One patient had pulmonary failure with pleural effusion and recovered within two weeks. Two of the three patients had positive cytology for cancer cells in the fluid. All three patients achieved partial remission with no repetition of the complication. The patients' recovery, response to treatment and the tumor reduction suggest that this complication was not due to disease progression