S. Algarra

8534 Background: Angiogenesis has an important role in melanoma progression. A prognostic value has been suggested for serum VEGF in melanoma. The novel agent bevacizumab (Bev) has demonstrated in combination with chemotherapy high activity in other tumors. We studied the combination of weekly paclitaxel (TXL) and bevacizumab (Bev) in previously treated metastatic melanoma patients (pts) and analyzed serum VEGF levels before and during treatment. Methods: TXL 70 mg/m2 weekly and Bev 10 mg/kg biweekly during 5 consecutive weeks every six weeks. VEGF levels pre-treatment and at response evaluation were analyzed with enzyme-linked immunoassays. Results: 13 pts have been treated: male/female: 4/9, median age: 45 (29–71), median PS ECOG: 2 (0–3), stage distribution M1b/ M1c: 2/11, high LDH levels: 8 pts. Median number of previous lines: 3 (1–6). Hematological toxicity: G III lymphopenia in 6 pts, G III leucopenia in 2 pts, G III thrombocytopenia in 1 pt and G I anemia in 3 pts. Non-hemat...

Objectives: To evaluate the feasibility and a possible activity range of combination irinotecan (CPT-11), oxaliplatin, and 5-FU in advanced colorectal cancer (ACC). Patients and Methods: A total of 53 patients (51% chemoresistant) were treated. Twenty-eight received monthly intravenous oxaliplatin (120 mg/m2) and CPT-11 (250 mg/m2) on day 1 and a course of 5-FU; these constituted the IRI250 group. Twenty-five received monthly intravenous oxaliplatin (120 mg/m2), CPT-11 (300 mg/m2) on day 1, and a course of 5-FU (IRI300 group). 5-FU administration was carried out as follows. Those with predominant hepatic disease (n = 32) received an intra-arterial infusion of 5-FU (2,500 mg/day on days 1–4); these were the IA-FU group. The remaining 21 patients received intravenous 5-FU (2,600 mg/m2 plus leucovorin 500 mg/m2 on days 1 and 15); these constituted the IV-FUFOL group. Results: Intention-to-treat response rate was 54.7% (4 CR, 7.5%). Twelve patients (22.5%) had stable disease; only 4 (7....

Unless carcinoid are in general slow-growing tumors, some cases could be frankly malignant. The commonest cause of death in patients suffering a carcinoid tumor is liver failure due to tumor progression. When tumors have a fast evolution a multidisciplinary approach must be perform. This case report is an example of this specific situation.

Clinical trials of drugs that influence coagulation and fibrinolysis pathways have been undertaken in patients with malignancy because these pathways are capable of influencing malignant progression. The validity of this concept was originally confirmed in experimental animal models of malignancy. Earlier pilot studies in human disease have been succeeded by definitive prospective randomized clinical trials that have revealed heterogeneity of responsiveness to anticoagulant and fibrinolytic agents that may be attributable to differences in mechanisms of interaction of the tumor cells of various types of malignancy with these pathways in vivo. In certain tumor types studied thus far, increased tumor response rates and prolongation of survival have been observed that suggest the possibility that substantial benefit may be realized from this treatment approach in patients with malignancy. In addition, the availability of newer and potentially more effective therapeutic agents holds promise for even greater gains in previously tested tumor types. The ability to design treatment regimens that correspond to defined mechanisms that pertain to specific tumor types should permit future studies to be designed rationally. Current data suggest that anticoagulant and fibrinolytic agents might reasonably be tested in tumor types characterized by the existence of a tumor cell-associated coagulation pathway with thrombin generation and conversion of fibrinogen to fibrin (such as small cell carcinoma of the lung). By contrast, protease inhibitors might reasonably be tested in tumor types characterized by expression of tumor cell plasminogen activators. Expansion of current views on the possible role of antithrombic drugs in cancer therapy is justified. For example, antithrombotic drugs classified as non-steroidal anti-inflammatory agents may inhibit carcinogenesis while polyanionic drugs with anticoagulant properties, such as suramin and heparin, may inhibit growth factor interactions with cells. Intriguing new opportunities clearly exist for interactions between clinical and basic investigators that may provide both novel biologic insights and improved patient care.

Fifty-one patients with small cell lung cancer (SCLC) were treated with alternating urokinase (UK)-cyclophosphamide-doxorubicin (Adriamycin, Adria Laboratories, Columbus, OH)-vincristine and cisplatin-etoposide-vincristine. UK was given as a loading dose of 3000 micrograms/kg body weight, followed by 3000 micrograms/kg/h for 6 hours. Thoracic irradiation with split technique (46 Gy) and prophylactic cranial irradiation (25 Gy) were administered to responding patients. A second staging was performed in patients exhibiting a clinical complete response (CR) after 1 year. In 27 patients with limited disease, there were 23 CR and 8 partial responses (PR) (CR, 85.1%; 66.2-95.8% at 95% confidence intervals); in 24 patients with extensive disease, there were 17 CR, 4 PR, and 3 cases with progression. Pathologically proven CR were observed in 59.2% patients with limited disease and 33.3% patients with extensive disease. Survival rates were as follows: in patients with limited disease, 1 year, 85.1%; 2 years, 55.5%; and 3 years, 25.9%; in patients with extensive disease, 1 year, 54.1; and 2 years, 16.9%. Median survival times were 26.3 months (patients with limited disease) and 13.3 months (patients with extensive disease). UK-related toxic effects included four episodes of mild to moderate bleeding, one allergic reaction, and one cerebrovascular accident. Myelotoxicity was severe, with a median of two episodes of Grade III-IV (World Health Organization classification) aplasia per patient. These results are consistent with a potential benefit of fibrinolytic therapy in combination with chemotherapy in patients with SCLC with limited disease. Additional trials are indicated.

Vinorelbine-cisplatin combination chemotherapy is a standard approach for the treatment of advanced non-small-cell lung cancer (NSCLC). The addition of paclitaxel as a third therapeutic agent seems promising. The aim of the present study was to evaluate the activity and toxicity of this new regimen. Forty-six nonselected and chemotherapy-naive patients with stage IV NSCLC and an Eastern Cooperative Oncology Group performance status of 0 to 2 were treated every 4 weeks with paclitaxel (135 mg/m2 given iv in 3 hours) and cisplatin (120 mg/m2 given iv in 6 hours) on day 1 and vinorelbine (30 mg/m2 given iv in 30 minutes) on days 1 and 15. All patients were evaluated for toxicity and response according to the intent-to-treat principle. An objective response was observed in 39% of the patients (95% CI: 25% to 55%). World Health Organization grade III to IV neutropenia, thrombocytopenia, and anemia occurred in 43%, 2%, and 17%, respectively. There was one treatment-related death. Nonhematologic toxicities were mild, mainly grade III nausea and vomiting in 20% of the patients. After a median follow-up period of 54 months, the median progression-free survival was 14.3 weeks and the median overall survival was 31.3 weeks. This three-drug chemotherapy combination is feasible, well tolerated, and shows activity in metastatic NSCLC.

Vemurafenib tolerability was assessed in a large, open-label, multicentre study in patients with BRAF (V600) mutated advanced melanoma. We investigated safety, tolerability and efficacy of vemurafenib in Spanish patients participating in that study. Patients with previously treated or treatment-naive, unresectable stage IIIC or stage IV, BRAF (V600) mutation-positive melanoma received vemurafenib 960 mg twice daily until disease progression, unacceptable toxicity, withdrawal of consent or death. The primary endpoint was safety; secondary endpoints included overall response rate (ORR), progression-free survival (PFS) and overall survival (OS). 301 Spanish patients were included, 70 % with M1c disease, 22 % with brain metastases and 51 % with prior systemic therapy for metastatic disease. Most frequent adverse events included fatigue (48 %), arthralgia (45 %), rash (41 %), photosensitivity (34 %) and skin neoplasms (21 %). Grade 3/4 adverse events occurred in 156 patients (52 %), including cutaneous squamous cell carcinoma (including keratoacanthoma; 16 %), fatigue (6 %) and arthralgia (5 %). The ORR was 28 % (95 % CI 23-34 %). Responses occurred in patients with brain metastases (18 %), elevated baseline lactate dehydrogenase (19 %) and poor performance status (15 %), and elderly patients (22 %). Median PFS was 5.8 (95 % CI 5.0-6.4) months; median OS was 10.5 (95 % CI 9.5-13.5) months. Our results for Spanish patients in the vemurafenib safety study indicate similar efficacy and a comparable safety profile in Spanish patients with no new safety signals compared with the overall population. Clinical benefit was demonstrated in poor-prognosis patients and in those with favourable baseline characteristics, suggesting that poor-prognosis patients may also benefit from vemurafenib treatment.

All melanoma patients must be confirmed histologically and resected according to Breslow. Sentinel node biopsy must be done when tumor is over 1 mm or if less with high-risk factors. Adjuvant therapy with interferon must be offered for patients with high-risk melanoma and in selected cases radiotherapy can be added. Metastatic melanoma treatment is guided by mutational BRAF status. BRAF wild type patients must receive anti-PD1 therapy and BRAF mutated patients BRAF/MEK inhibitors or anti-PD1 therapy. Up to 10 years follow up is recommended for melanoma patients with dermatologic examinations and physical exams.

Paclitaxel-cisplatin is considered to be a standard therapy for metastatic non-small-cell lung cancer (NSCLC). The aim of this study was to evaluate the activity and toxicity of this combination with vinorelbine or gemcitabine as front-line therapy in brain metastases from NSCLC. Twenty-six chemotherapy-naive patients with an ECOG performance status of 0-2 were treated with paclitaxel (135 mg/m(2)) on day 1, cisplatin (120 mg/m(2)) on day 1, and either vinorelbine (30 mg/m(2)) on days 1 and 15 or gemcitabine (800 mg/m(2)) on days 1 and 8. Whole-brain irradiation was offered early in case of progression and later as consolidation treatment. All patients were evaluated for toxicity and 25 for response. An intracranial response rate was observed in 38% of the patients (95% CI: 22-59%). WHO grade 3-4 neutropenia and thrombocytopenia occurred in 31 and 4% of the patients, respectively. There was one treatment-related death. Non-hematological toxicities were mild. After a median follow-up of 46 months, the median overall survival for all patients was 21.4 weeks and the median time to progression was 12.8 weeks. Paclitaxel and cisplatin combined with vinorelbine or gemcitabine as front-line therapy in brain metastases seem to achieve responses similar to those for extracranial disease, suggesting a meaningful role in this setting.

Surrogate biomarkers of efficacy are needed for anti-PD1/PD-L1 therapy, given the existence of delayed responses and pseudo-progressions. We evaluated changes in serum IL-8 levels as a biomarker of response to anti-PD-1 blockade in melanoma and non-small-cell lung cancer (NSCLC) patients. Metastatic melanoma and NSCLC patients treated with nivolumab or pembrolizumab alone or nivolumab plus ipilimumab were studied. Serum was collected at baseline; at 2-4 weeks after the first dose; and at the time-points of response evaluation. Serum IL-8 levels were determined by sandwich ELISA. Changes in serum IL-8 levels were compared with the Wilcoxon test and their strength of association with response was assessed with the Mann-Whitney test. Accuracy of changes in IL-8 levels to predict response was estimated using receiver operation characteristics curves. Twenty-nine melanoma patients treated with nivolumab or pembrolizumab were studied. In responding patients, serum IL-8 levels significantly decreased between baseline and best response (P <0.001), and significantly increased upon progression (P =  0.004). In non-responders, IL-8 levels significantly increased between baseline and progression (P =  0.013). Early changes in serum IL-8 levels (2-4 weeks after treatment initiation) were strongly associated with response (P <0.001). These observations were validated in 19 NSCLC patients treated with nivolumab or pembrolizumab (P =  0.001), and in 15 melanoma patients treated with nivolumab plus ipilimumab (P <0.001). Early decreases in serum IL-8 levels were associated with longer overall survival in melanoma (P =  0.001) and NSCLC (P =  0.015) patients. Serum IL-8 levels also correctly reflected true response in three cancer patients presenting pseudoprogression. Changes in serum IL-8 levels could be used to monitor and predict clinical benefit from immune checkpoint blockade in melanoma and NSCLC patients.

From 1982 to 1989, 68 patients were treated with the diagnosis of breast cancer. 57 were premenopausal and 11 postmenopausal. The most frequent stage was T2N1 (44.1%) followed by T1N1 (20.6%). The mean dosage of chemotherapy given were 91.2% for cyclophosphamide, 88% for methotrexate and 94% for 5-fluorouracil. The treatment was well tolerated and the most frequent toxicity encountered was leukopenia. The disease free survival were 89.4% at 96 month for premenopausal and 63.3% at 68 month for postmenopausal. We have not seen any differences in the disease free survival in relation to the size of the tumor or the status of the hormonal receptors of the tumor. The most important prognostic factor were the number of positive axilar nodes affected and the dosage of chemotherapy.

Small cell lung cancer is one of the most aggressive solid tumors because of its rapid growth and early tendency to spread to distant organs. Nonetheless, it is also one of the most sensitive tumors to chemotherapy and radiotherapy, which can give patients with limited disease a chance to become long-term survivors. These characteristics have made this tumor a clinical model to explore various treatment strategies, including concomitant chemotherapy and radiotherapy, alternant chemotherapy, high-dose chemotherapy with hematologic support, or use of whole-brain prophylactic radiotherapy. In addition, in recent years, small cell lung cancer has been used as a platform to develop some new targeted therapy agents or immunotherapeutic approaches.

Cancer patients often show an imbalance condition between coagulation system and fibrinolysis which causes a prothrombotic state. Different molecular factors like von Willebrand factor (vWf), presenting higher plasmatic rates in these patients, play an important role in this situation. During active angiogenesis taking place in tumor growth, the vascular endothelial growth factor (VEGF) and the fibroblast growth factor (FGF-2) contribute to the proliferation and differentiation of endothelial tissue, the main vWf producer, promoting increased rates of vWf in the serum of neoplastic patients. Recently vWf's contribution to tumor cells and platelet adhesion has been described. In this process, the discovery of platelet, endothelial and tumor cell membrane integrins and their implication in cellular adhesion has represented a major step in demonstrating how blood clotting and platelet aggregation are mediated by tumor cell and platelet linkage. Migration properties acquired by tumo...

Tumour response evaluation after chemotherapy has become crucial in the development of many drugs. In contrast to the standard bidimensional WHO criteria, the recently described Response Evaluation Criteria In Solid Tumors are based on unidimensional measurements. The aim of the present study was to compare both methods in patients with metastatic non-small cell lung cancer. One hundred and sixty-four patients treated with two cisplatin-paclitaxel-based chemotherapy schedules between June 1994 and December 2000 were analysed. The measurements were reviewed by an independent panel of radiologists. Patient characteristics were: median age of 55 years (range 24-77 years) and a male to female ratio of 129 : 35. Adenocarcinoma and squamous carcinoma were the most common histologies. Vinorelbine was the third drug used in 77 patients and gemcitabine in 87. The ratio unidimensional/bidimensional was as follows: response 85 : 85; stable disease 32 : 32; progression 47 : 42 and not assessabl...

A phase II study of postoperative high-dose carmustine (HDBCNU), intracarotid cisplatin (CDDP), and radical radiotherapy in patients with high-grade glioma was performed. Patients underwent 4-6 consecutive days of blood hematopoietic progenitor cell (HPC) apheresis without prior mobilization. Chemotherapy included intracarotid CDDP, 60 mg/m2, and BCNU, 900 mg/m2. HPC were infused 48 h after HDBCNU. Whole brain irradiation, up to 50 Gy, was started on the 8th day after HPC infusion. With a median follow-up time of 44 months, median overall survival was 15.5 months. Eight patients (23.5%) are alive free of disease 2-6 years after treatment (seven out of 25 patients with glioblastoma multiforme and one out of nine patients with anaplastic astrocytoma). Survival was influenced by young age, good performance and complete surgical resection. Two patients (5.8%) died of therapy-related complications. Acute hematological toxicity of HDBCNU was moderate, with a full recovery on day 26. No ac...

Activation of the ERK1/2 pathway is involved in malignant transformation both in vitro and in vivo. Little is known about the role of activated ERK1/2 in non-small cell lung cancer (NSCLC). The purpose of this study was to characterise the extent of the activation of ERK1/2 by immunohistochemistry in patients with NSCLC, and to determine the relationship of ERK1/2 activation with clinicopathological variables. Specimens from 111 patients with NSCLC (stages I-IV) were stained for P-ERK. Staining for epidermal growth factor receptor (EGFR) and Ki-67 was also performed. In all, 34% of the tumour specimens showed activation for ERK1/2, while normal lung epithelial tissue was consistently negative. There was a strong statistical correlation between nuclear and cytoplasmic P-ERK staining and advanced stages (P<0.05 and P<0.001, respectively), metastatic hilar or mediastinal lymph nodes (P<0.01, P<0.001), and higher T stages (P<0.01, P<0.001). We did not find correlation ...

As a result of therapeutic advances, a revolution is taking place in the lung cancer field with major implications for pathologic diagnosis and tissue management. We report a case of a non-small cell lung carcinoma patient with coexistence of EGFR mutations and ALK-EML4 rearrangements that responded to EGFR inhibitors and in which the development of a new resistance mutation in exon 20 of EGFR-determined treatment resistance. All the molecular determinations were performed in cytological samples. To our knowledge, this is the first case reported with these characteristics, and the 11th case described with coexistence of EGFR mutations and ALK-EML4 rearrangements. The EGFR L858R mutation in exon 21 was found at diagnosis, and the patient presented a 4-year response to erlotinib. On progression, the T790M resistance mutation in the EGFR exon 20 was also confirmed in cytological samples. At this point, fluorescence in situ hybridization also detected ALK-EML4 translocation. This case emphasizes the usefulness of cytological samples for molecular analysis in lung adenocarcinoma, as well as the relevance of repeating biopsies/fine-needle aspirations in tumor recurrences to assess the mutation profile of the disease.

Around 50% of cutaneous melanomas harbor the BRAF(V600E) mutation and can be treated with BRAF inhibitors. DNA carrying this mutation can be released into circulation as cell-free BRAF(V600E) (cfBRAF(V600E)). Droplet digital PCR (ddPCR) is an analytically sensitive technique for quantifying small concentrations of DNA. We studied the plasma concentrations of cfBRAF(V600E) by ddPCR in patients with melanoma during therapy with BRAF inhibitors. Plasma concentrations of cfBRAF(V600E) were measured in 8 controls and 20 patients with advanced melanoma having the BRAF(V600E) mutation during treatment with BRAF inhibitors at baseline, first month, best response, and progression. The BRAF(V600E) mutation was detected by ddPCR even at a fractional abundance of 0.005% in the wild-type gene. Agreement between tumor tissue BRAF(V600E) and plasma cfBRAF(V600E) was 84.3%. Baseline cfBRAF(V600E) correlated with tumor burden (r = 0.742, P < 0.001). cfBRAF(V600E) concentrations decreased significantly at the first month of therapy (basal median, 216 copies/mL; Q1-Q3, 27-647 copies/mL; first response median, 0 copies/mL; Q1-Q3, 0-49 copies/mL; P < 0.01) and at the moment of best response (median, 0 copies/mL; Q1-Q3, 0-33 copies/mL; P < 0.01). At progression, there was a significant increase in the concentration of cfBRAF(V600E) compared with best response (median, 115 copies/mL; Q1-Q3, 3-707 copies/mL; P = 0.013). Lower concentrations of basal cfBRAF(V600E) were significantly associated with longer overall survival and progression-free survival (27.7 months and 9 months, respectively) than higher basal concentrations (8.6 months and 3 months, P < 0.001 and P = 0.024, respectively). cfBRAF(V600E) quantification in plasma by ddPCR is useful as a follow-up to treatment response in patients with advanced melanoma.

Interleukin-8 (IL8) is a chemokine produced by malignant cells of multiple cancer types. It exerts various functions in shaping protumoral vascularization and inflammation/immunity. We evaluated sequential levels of serum IL8 in preclinical tumor models and in patients to assess its ability to estimate tumor burden. IL8 levels were monitored by sandwich ELISAs in cultured tumor cells supernatants, tumor-xenografted mice serum, and in samples from 126 patients with cancer. We correlated IL8 serum levels with baseline tumor burden and with treatment-induced changes in tumor burden, as well as with prognosis. IL8 concentrations correlated with the number of IL8-producing tumor cells in culture. In xenografted neoplasms, IL8 serum levels rapidly dropped after surgical excision, indicating an accurate correlation with tumor burden. In patients with melanoma (n = 16), renal cell carcinoma (RCC; n = 23), non-small cell lung cancer (NSCLC; n = 21), or hepatocellular carcinoma (HCC; n = 30),...

In a randomized phase III study (BREAK-3), dabrafenib showed prolonged progression-free survival (PFS) (median 5.1 versus 2.7 months; hazard ratio = 0.30; 95% confidence interval 0.18-0.53; P < 0.0001) compared with dacarbazine (DTIC) in patients with BRAF V600E metastatic melanoma. Assessing how these results are transformed into a real health benefit for patients is crucial. The EORTC QLQ-C30 questionnaire assessed quality of life (QoL) at baseline and follow-up visits. For DTIC, all functional dimensions except role dimension worsened from baseline at follow-up. For dabrafenib, all functionality dimensions remained stable relative to baseline or improved at week 6; mean change in seven symptom dimensions improved from baseline, with appetite loss, insomnia, nausea and vomiting, and pain showing the greatest improvement. In the DTIC arm, symptom dimensions were unchanged or worsened from baseline for all symptoms except pain (week 6), with the greatest exacerbations observed for fatigue and nausea and vomiting. Mixed-model-repeated measures analyses showed significant (P < 0.05) and/or clinically meaningful improvements from baseline in favor of dabrafenib for emotional and social functioning, nausea and vomiting, appetite loss, diarrhea, fatigue, dyspnea, and insomnia at weeks 6 and/or 12. After crossing over to dabrafenib upon progression (n = 35), improvements in all QoL dimensions were evident after receiving dabrafenib for 6 (n = 31) to 12 (n = 25) weeks. This first reported QoL analysis for a BRAF inhibitor in metastatic melanoma demonstrates that the high tumor response rates and PFS superiority of dabrafenib over DTIC is not only a theoretical advantage, but also transforms in a rapid functional and symptomatic benefit for the patient. NCT01227889.

Pretreated advanced melanoma is a poor prognosis scenario with few, if any, active therapeutic options. The antibody against vascular endothelial growth factor, bevacizumab, has demonstrated increased activity in combination with chemotherapy in many tumors. We intended to evaluate the activity of the combination of weekly paclitaxel and bevacizumab in previously treated metastatic melanoma. Patients with previously treated metastatic melanoma received paclitaxel 70 mg/m(2) weekly and bevacizumab 10 mg/kg biweekly for 5 consecutive weeks every 6 weeks. Twelve patients were treated. Two patients (16.6%) achieved a partial response and 7 patients (58.3%) stable disease. Responses were seen in soft tissue, lung and brain metastases. Median disease-free and overall survival times were 3.7 and 7.8 months, respectively. Treatment was well tolerated. Main toxicities were grade 3 asymptomatic lymphopenia in 6 patients, grade 3 leucopenia in 2 patients, and grade 3 thrombocytopenia in 1 patient. Our preliminary results suggest that the combination of bevacizumab and weekly paclitaxel is active and safe in patients with metastatic melanoma, warranting further investigation.

Predictive biomarkers can play a key role in individualized disease monitoring. Unfortunately, the use of biomarkers in clinical settings has thus far been limited. We have previously shown that mechanism-based pharmacokinetic/pharmacodynamic modeling enables integration of nonvalidated biomarker data to provide predictive model-based biomarkers for response classification. The biomarker model we developed incorporates an underlying latent variable (disease) representing (unobserved) tumor size dynamics, which is assumed to drive biomarker production and to be influenced by exposure to treatment. Here, we show that by integrating CT scan data, the population model can be expanded to include patient outcome. Moreover, we show that in conjunction with routine medical monitoring data, the population model can support accurate individual predictions of outcome. Our combined model predicts that a change in disease of 29.2% (relative standard error 20%) between two consecutive CT scans (i.e., 6-8 weeks) gives a probability of disease progression of 50%. We apply this framework to an external dataset containing biomarker data from 22 small cell lung cancer patients (four patients progressing during follow-up). Using only data up until the end of treatment (a total of 137 lactate dehydrogenase and 77 neuron-specific enolase observations), the statistical framework prospectively identified 75% of the individuals as having a predictable outcome in follow-up visits. This included two of the four patients who eventually progressed. In all identified individuals, the model-predicted outcomes matched the observed outcomes. This framework allows at risk patients to be identified early and therapeutic intervention/monitoring to be adjusted individually, which may improve overall patient survival. Cancer Res; 75(12); 2416-25. ©2015 AACR.

A 24-mer (antisense) phosphorothioate oligonucleotide (ODN) corresponding to the codons 2-9 of the c-myb gene was evaluated for its effects on the growth of a human Burkitt lymphoma cell line (Raji) in vitro. Raji cells incubated with different concentrations of c-myb antisense ODN (5-15 mu g/ml) for 24-72 h showed a significant dose-dependent decrease in growth. The same concentrations of control (sense) or scrambled c-myb phosphorothioate ODNs did not inhibit Raji cell growth. The c-myb antisense ODN, but not the control ODNs, significantly decreased c-myb mRNA levels in treated cells as determined by RT-PCR. Additionally, the c-myb antisense ODN induced apoptosis of Raji cells as demonstrated by i) flow cytometry to enumerate the A(o) (apoptotic cell population) population of propidium iodide stained cells; ii) electron microscopy to evaluate the cell morphology; and iii) DNA fragmentation pattern. Thus, an antisense c-myb ODN causes significant growth inhibition of Burkitt lymph...

The use of hematopoietic growth factors (HGFs) in the allogeneic transplant setting has sometimes been avoided for fear of stimulating leukemic cell growth and intensifying graft-vs.-host disease (GVHD). However, neither an increase in relapse rate nor an aggravation of GVHD has been routinely described when HGFs are used after allogeneic bone marrow transplantation (allo-BMT). Early outcomes after HLA-matched allo-BMT in 26 patients with hematologic malignancies treated with recombinant human granulocyte colony-stimulating factor (rhG-CSF) or recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) from the day of transplantation were analyzed. Results were compared to those from a series of 38 patients treated earlier with an identical approach, but not scheduled to receive HGFs after transplantation. All patients received a preparative regimen consisting of etoposide, cyclophosphamide, and total-body irradiation and GVHD prophylaxis with cyclosporine and a sh...

We report here a taxol-bevacizumab-responsive metastatic melanoma case. Although the patient had been heavily pretreated for two years, she did not show any stabilisation or objective response of her disease. After treatment with taxol and bevacizumab combination an impressive response was obtained.