Search

Background: Cetuximab enhances the efficacy of chemotherapy in several cancer types. This trial assessed the activity of cetuximab and chemotherapy in advanced gastric cancer.Methods: Patients with previously untreated, metastatic, gastric cancer received cetuximab 400 mg m(-2) at first infusion followed by weekly infusions of 250 mg m(-2) combined with FUFOX (oxaliplatin 50 mg m(-2), 5-FU 2000 mg m(-2), and DL-folinic acid 200 mg m(-2) d1, 8, 15 and 22 qd36). The primary endpoint was tumour response.Results: Overall, 52 patients were enrolled. The most common grade 3/4 toxicities were diarrhoea (33%), and skin toxicity (24%). Efficacy was evaluable in 46 patients who showed a response rate of 65% (CI 95%: 50-79%) including four complete responses. Time to progression (TTP) was 7.6 months (CI 95%: 5.0-10.1 months) and overall survival (OS) was 9.5 months (CI 95%: 7.9-11.1 months). Epidermal growth factor receptor (EGFR) was detectable in 60% of tumours but showed no correlation with treatment outcome. A KRAS mutation was found in only 1 of 32 (3%) tumour samples analysed.Conclusion: Cetuximab plus FUFOX showed an interesting high response rate in metastatic gastric cancer. Cetuximab plus platinum-fluoropyrimidine chemotherapy is at present being investigated in a phase III randomised controlled trial. [ABSTRACT FROM AUTHOR]

Copyright of Wiener Klinisches Magazin is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Aims: Recent results generated in a mouse model suggest that tumour angiogenesis/vasculogenesis can be initiated and maintained by bone marrow derived endothelial progenitor cells. This present study investigated the distribution and frequency of CD133 positive endothelial progenitor cells in patients with non-small cell lung cancer (NSCLC) (tumour tissue and tumour free lung regions) and healthy controls using fresh frozen specimens. The novel marker CD133 identifies human haemopoetic precursor cells, in addition to human endothelial progenitor cells. Methods: Seventy nine lung cancer specimens and 66 adjacent histologically tumour free tissues of the same patient cohort were analysed; 11 postmortem specimens from control patients who did not suffer from malignant disease served as controls. Cryostat sections were stained for CD133, CD31, vascular endothelial growth factor receptor 2 (VEGFR-2; KDR), p53, and the proliferation marker Ki-67, and the correlations were analysed. Results: Forty three of 63 evaluable tumour specimens had increased numbers of CD133 positive cells and in some cases capillary forming CD133 positive structures were detectable. In addition, 30 of 63 specimens had raised expression of KDR and 29 of 63 had increased MVD. Increased CD133 expression marginally correlated with raised KDR expression but not with p53 and Ki-67. Conclusion: A significant increase in CD133 positive cells was documented in patients with NSCLC, suggesting an involvement of endothelial progenitor cells in tumour vasculogenesis and tumour growth in these patients. [ABSTRACT FROM AUTHOR]

The ability of cells to readjust their volume after swelling, a phenomenon known as regulatory volume decrease (RVD), is a fundamental biological achievement guaranteeing survival and function of cells under osmotic stress. This article reviews the mechanisms of RVD in mammalian cells with special emphasis on the activation of ion channels during RVD. [ABSTRACT FROM AUTHOR]

The present study has been performed to test for the influence of serotonin on the potential difference across the cell membrane (PD) of Madin-Darby canine kidney (MDCK)-cells. Under control conditions PD averages −48.6±0.6 mV ( n=98). Increasing extracellular potassium concentration from 5.4 to 10 and 20 mmol/l depolarizes the cell membrane by +6.3±0.6 mV ( n=6) and +14.1±1.0 mV ( n=12), respectively. The cell membrane is transiently hyperpolarized to −67.8±0.8 mV ( n=63) by 1 μmol/l serotonin. In the presence of serotonin, increasing extracellular potassium concentration from 5.4 to 20 mmol/l depolarizes the cell membrane by +26.4±1.0 mV ( n=11). 1 mmol/l barium depolarizes the cell membrane by +15.7±1.3 mV ( n=17) and abolishes the effect of step increases of extracellular potassium concentration from 5.4 to 10 mmol/l. In the presence of barium, serotonin leads to a transient hyperpolarization by −26.3±1.0 mV ( n=16). During this transient hyperpolarization, the cell membrane is sensitive to extracellular potassium concentration despite the continued presence of barium. 10 μmol/l methysergide hyperpolarize the cell membrane by −7.2±2.0 mV ( n=6). In the presence of 10μmol/l methysergide, the effect of serotonin is virtually abolished (+0.4±0.9 mV, n=6). 1 μmol/l ketanserin, a 5-HT receptor blocking agent, ICS 205-930, a 5-HT receptor blocking agent, and phentolamine, an unspecific α-receptor blocking agent, do not significantly modify the effect of serotonin. In the nominal absence of extracellular calcium, the effect of serotonin is markedly reduced. In conclusion, serotonin hyperpolarizes MDCK-cells by increasing apparent potassium conductance. This effect is transmitted by 5-HT receptors and depends on extracellular calcium. [ABSTRACT FROM AUTHOR]

In NIH 3T3 fibroblasts expressing the Ha- ras oncogene (+ ras) bradykinin leads to sustained oscillations of cell membrane potential due to oscillations of intracellular Ca with subsequent activation of Ca-sensitive K channels. In cells not expressing the oncogene (- ras), bradykinin leads only to a single transient hyperpolarization of the cell membrane. The present study has been performed to elucidate the possible interaction of cell volume, intracellular pH and bradykinin-induced oscillations of the cell membrane potential. Bradykinin leads to cell shrinkage and intracellular alkalinization of both + ras cells and − ras cells. Inhibition of Na/H exchanger by HOE 694 abolishes the bradykinin-induced alkalinization but does not significantly interfere with the bradykinin-induced oscillations of cell membrane potential. In contrast, prevention of bradykinin-induced cell shrinkage by simultaneous reduction of extracellular osmolarity blunts the oscillations. Thus, cell shrinkage stimulates bradykinin-induced oscillations of cell membrane potential. On the other hand, cell shrinkage alone does not elicit oscillations unless, in addition, Ca entry is stimulated by ionomycin. [ABSTRACT FROM AUTHOR]

Expression of the Ha-ras oncogene has been reported to stimulate the dimethylamiloride sensitive Na/H exchanger and Na, K, 2Cl cotransport, both transport systems which are involved in cell volume regulation. The present study has been performed to test for an influence of ras oncogene expression on cell volume regulation in NIH 3T3 fibroblasts expressing the Ha-ras oncogene (+ ras). As controls served NIH 3T3 fibroblasts not expressing the ras oncogene (− ras). In isotonic extracellular fluid, the cell volume of + ras cells (2.70±0.08 pl) is significantly greater than the cell volume of −ras cells (2.04±0.10 pl). Both, + ras and − ras cells exhibit a regulatory cell volume increase in hypertonic extracellular fluid and a regulatory cell volume decrease in hypotonic extracellular fluid. The regulatory cell volume decrease is inhibited by 1 mmol/l quinidine and barium, the regulatory cell volume increase is inhibited in − ras and + ras cells by dimethyl-amiloride (100 μmol/l) and, only in + ras cells, by furosemide (100 μmol/l) and bumetanide (10 μmol/l). In conclusion, expression of the ras oncogene leads to a shift of the set point for cell volume regulation to greater cell volumes, which may contribute to the activation of the Na/H exchanger and Na, K, 2Cl cotransport. [ABSTRACT FROM AUTHOR]

In NIH fibroblasts expressing the ras oncogene bradykinin leads to sustained, calcium-dependent oscillations of cell membrane potential by oscillating activity of calcium sensitive potassium channels. The present study has been performed to further analyse the underlying mechanisms. In cells expressing the oncogene, but not in NIH fibroblasts not expressing the oncogene, bradykinin elicits calcium oscillations, which are detected by fura-2 fluorescence and amplified by a decrease of extracellular sodium activity. These calcium oscillations are dependent on the presence of extracellular calcium and are inhibited by lanthanum ions. It is concluded that in cells expressing the ras oncogene, bradykinin activates lanthanum sensitive calcium entry from the extracellular space. Ras oncogene expression leads to enhanced bradykinin-induced formation of both, 1, 4, 5 inositoltrisphosphate and 1, 3, 4, 5 inositoltetrakisphosphate, an effect probably accounting for the oscillations of intracellular calcium activity. [ABSTRACT FROM AUTHOR]

ATP activates K channels by increasing intracellular calcium activity in Madin Darby canine kidney (MDCK) cells. The present study has been performed to test for the involvement of G-proteins and of protein kinase C in the intracellular transmission of these effects. To this end, the effect of ATP on intracellular calcium and K channel activity has been studied in cells pretreated with the phorbol ester 12- O-tetradecanoylphorbol 13-acetate (TPA) and/or pertussis toxin. The ATP-induced increase of intracellular calcium is not significantly affected by pretreatment with pertussis toxin, is significantly blunted by pretreatment with TPA and is abolished by pretreatment with both pertussis toxin and the phorbol ester. The ATP activation of K channels is similarly blunted by pretreatment with TPA, but is not abolished by pretreatment with both the phorbol ester and pertussis toxin. Furthermore, the ATP-induced hyperpolarization is not abolished in cells pretreated with both pertussis toxin and TPA. In those cells, ATP may activate K channels by calcium-independent mechanisms or lead to localized increases of intracellular calcium sufficient to activate the K channels but escaping detection with fura-2 fluorescence. [ABSTRACT FROM AUTHOR]

Gastric cancer is still a devastating disease. Two thirds of the patients are diagnosed in a locally advanced or metastatic stage. Even if surgery is possible, long-term survival is low. Optimal therapy in a curative and a palliative setting is still not clear yet. ASCO 2010 could shed some light on optimal chemotherapy and the introduction of molecular targeted therapy. The aim of this article is to summarize the most important publications at this year's ASCO annual meeting and to put them into context of current therapeutic strategies. [ABSTRACT FROM AUTHOR]

Overall survival of patients suffering from gastric cancer is still poor. Two-thirds of patients are diagnosed in a locally advanced stage or with metastatic tumour. But even in patients with operable disease recurrence rate is high. To increase the prognosis of this devastating disease much effort has been put in the development of curative and palliative therapy concepts recently. The aim of this article is to summarize the most important publications at this year's ASCO meeting and to put them into context of current therapeutic strategies. [ABSTRACT FROM AUTHOR]

Gastric cancer is still one of the predominant causes of death on account of gastrointestinal neoplasias. In recent years, chemotherapy and radiotherapy have substantially improved the outcome in operable gastric cancer patients. A benefit in median overall survival is reported for perioperative chemotherapy as well as for postoperative adjuvant radio-chemotherapy. But there is still a controversy about the best treatment sequence. The aim of this paper is to critically review current literature, to discuss the pros and cons of neoadjuvant (preoperative) or postoperative adjuvant therapy and to give treatment recommendations based on large phase III trials. [ABSTRACT FROM AUTHOR]