MATCHINGS IN REGULAR GRAPHS: MINIMIZING THE PARTITION FUNCTION

For a graph G on v(G) vertices let m(k)(G) denote the number of matchings of size k, and consider the partition function M-G(lambda) = Sigma(n)(k=0)m(k)(G)lambda(k). In this paper we show that if G is a d-regular graph and 0 1/v(Kd+1) ln MKd+1(lambda).The same inequality holds true if d = 3 and lambda < 0.3575. More precise conjectures are also given

Carfilzomib and dexamethasone versus bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma (ENDEAVOR): And randomised, phase 3, open-label, multicentre study

Background: Bortezomib with dexamethasone is a standard treatment option for relapsed or refractory multiple myeloma. Carfilzomib with dexamethasone has shown promising activity in patients in this disease setting. The aim of this study was to compare the combination of carfilzomib and dexamethasone with bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma. Methods: In this randomised, phase 3, open-label, multicentre study, patients with relapsed or refractory multiple myeloma who had one to three previous treatments were randomly assigned (1:1) using a blocked randomisation scheme (block size of four) to receive carfilzomib with dexamethasone (carfilzomib group) or bortezomib with dexamethasone (bortezomib group). Randomisation was stratified by previous proteasome inhibitor therapy, previous lines of treatment, International Staging System stage, and planned route of bortezomib administration if randomly assigned to bortezomib with dexamethasone. Patients received treatment until progression with carfilzomib (20 mg/m2 on days 1 and 2 of cycle 1; 56 mg/m2 thereafter; 30 min intravenous infusion) and dexamethasone (20 mg oral or intravenous infusion) or bortezomib (1·3 mg/m2; intravenous bolus or subcutaneous injection) and dexamethasone (20 mg oral or intravenous infusion). The primary endpoint was progression-free survival in the intention-to-treat population. All participants who received at least one dose of study drug were included in the safety analyses. The study is ongoing but not enrolling participants; results for the interim analysis of the primary endpoint are presented. The trial is registered at ClinicalTrials.gov, number NCT01568866. Findings: Between June 20, 2012, and June 30, 2014, 929 patients were randomly assigned (464 to the carfilzomib group; 465 to the bortezomib group). Median follow-up was 11·9 months (IQR 9·3-16·1) in the carfilzomib group and 11·1 months (8·2-14·3) in the bortezomib group. Median progression-free survival was 18·7 months (95% CI 15·6-not estimable) in the carfilzomib group versus 9·4 months (8·4-10·4) in the bortezomib group at a preplanned interim analysis (hazard ratio [HR] 0·53 [95% CI 0·44-0·65]; p<0·0001). On-study death due to adverse events occurred in 18 (4%) of 464 patients in the carfilzomib group and in 16 (3%) of 465 patients in the bortezomib group. Serious adverse events were reported in 224 (48%) of 463 patients in the carfilzomib group and in 162 (36%) of 456 patients in the bortezomib group. The most frequent grade 3 or higher adverse events were anaemia (67 [14%] of 463 patients in the carfilzomib group vs 45 [10%] of 456 patients in the bortezomib group), hypertension (41 [9%] vs 12 [3%]), thrombocytopenia (39 [8%] vs 43 [9%]), and pneumonia (32 [7%] vs 36 [8%]). Interpretation: For patients with relapsed or refractory multiple myeloma, carfilzomib with dexamethasone could be considered in cases in which bortezomib with dexamethasone is a potential treatment option. Funding: Onyx Pharmaceuticals, Inc., an Amgen subsidiary

Interleukin 4 down-regulates expression of c-kit and autocrine stem cell factor in human colorectal carcinoma cells

Stem cell factor (SCF) is a cytokine which plays an important role in the development of precursor cells. We have investigated the expression of SCF and its receptor, the c-kit proto-oncogene, in human colorectal carcinoma cell lines. Using reverse transcription-PCR, we confirmed the expression of c-kit in two lines (151 74T and 151 034) and of SCF in 9 of 1 1 cell lines tested. In a Northern blot, a single transcript of 6.6 kb was detected for SCF mRNA. In addition, two lines (LS1 74T and HT29) synthesized SCF protein, as detected by Western blot analysis. SCF stimulated proliferation and colony formation of 151 74T in a dose-dependent manner up to 160%. A half-maximal effect was obtained with about 5.5 ng/ml of SCF under both growth conditions. 151 74T cells expressed the Mr 1 45,000 c-kit protein on the cell surface and a neutralizing anti-c-kit mAb inhibited colony formation of 151 74T by 40%. Interleukin 4 (11-4) completely inhibited SCF-induced proliferation of 151 74T cells. Interestingly, 11-4 induced an almost complete down-regulation of both c-kit and SCF expression in [Si 74T. Our findings suggest that in LS1 74T cells, an SCF-mediated autocrine loop is functional and that 11-4 down-regulates the expression of both the receptor and the ligand of this circuit

Modulated Electro-Hyperthermic (mEHT) Treatment in the Therapy of Inoperable Pancreatic Cancer Patients—A Single-Center Case-Control Study

Our present oncological treatment arsenal has limited treatment options for pancreatic ductal adenocarcinoma (PDAC). Extended reviews have shown the benefits of hyperthermia for PDAC, supporting the perspectives with the improvements of the treatment possibilities. METHODS: A retrospective single-center case-control study was conducted with the inclusion of 78 inoperable PDAC patients. Age-, sex-, chemotherapy-, stage-, and ascites formation-matched patients were assigned to two equal groups based on the application of modulated electro-hyperthermia (mEHT). The EHY2030 mEHT device was used. RESULTS: A trend in favor of mEHT was found in overall survival (p = 0.1420). To further evaluate the potential beneficial effects of mEHT, the presence of distant metastasis or ascites in the patients’ oncological history was investigated. Of note, mEHT treatment had a favorable effect on patients’ overall survival in metastatic disease (p = 0.0154), while less abdominal fluid responded to the mEHT treatment in a more efficient way (p ≤ 0.0138). CONCLUSION: mEHT treatment was associated with improved overall survival in PDAC in our single-center retrospective case-control study. The outcome measures encourage us to design a randomized prospective clinical study to further confirm the efficiency of mEHT in this patient cohort