Polatholmgaard1392

BACKGROUND BTH1677 is a beta-glucan pathogen-associated molecular pattern (PAMP) being evaluated as a novel immunotherapy of cancer. check details We previously described that the presence of antibodies against beta-glucan (ABA) in serum is necessary for BTH1677 antitumoral activity. We hypothesized that infusion of immunoglobulin can reinstate responses to BTH1677 in individuals with low ABA levels. PATIENTS AND METHODS We report two single-patient studies one in a patient with metastatic colorectal cancer who received BTH1677, combined with tumor targeting antibody cetuximab; and a second in a patient with metastatic neuroendocrine tumor who received BTH1677 combined with immune checkpoint inhibitor pembrolizumab. RESULTS The patients had low serum titers of ABA and low innate immune effector functionality induced by BTH1677. Addition of intravenous immunoglobulins restored innate immune activity of BTH1677 and induced clinically meaningful anti-tumoral activity, with long-term disease control. CONCLUSION Infusion of immunoglobulin can restore activity of BTH1677 in individuals with low serum ABA level. BACKGROUND/AIM Radiotherapy for soft tissue sarcomas (STS) of the hand is thought to be associated with poor function. The aim of this study was to compare the long-term functional outcome in patients with and without radiotherapy. PATIENTS AND METHODS At long-term follow-up (mean 10±5 years), 33 (13 males, 20 female) patients, were alive for review. The mean patient age at surgery was 33±17 years and 13 (39%) patients received radiotherapy (mean dose 55±6 Gy). RESULTS Postoperatively, the mean QuickDASH and MSTS93 were 7±8 and 92±8%, respectively. Comparing patients with and without radiotherapy, there was no difference (p>0.05) between the mean QuickDASH (5±5 vs. 8±9) or MSTS93 (93±9% vs. 91±8%). Surgical complication occurred more commonly in patients with radiotherapy (46% vs. 15%, p=0.10). CONCLUSION The use of radiotherapy was associated with a higher rate of complications, however, was not associated with a worse long-term functional outcome in patients with hand STS. BACKGROUND/AIM We have previously found elevated levels of endoglin (CD105) in the prostate cancer (PC) tissue of men with poor prognosis, compared to men with indolent disease. Herein, we examined whether plasma levels of the soluble form of CD105 (sCD105) differ according to the PC grade at diagnosis. PATIENTS AND METHODS We measured sCD105 in 73 subjects with biopsy-confirmed PC at the Durham, North Carolina, Veteran Affairs Health System. The association between sCD105 and intermediate/high-grade PC risk [Gleason Group (GG) 2-5 vs. 1] was examined using regression models. RESULTS Of 73 men, 27 had low-grade PC and 46 high-grade PC. Higher GG was linked to lower sCD105 (GG1 6938 pg/ml, GG2-3 6150 pg/ml, GG4-5 5554 pg/ml; p=0.012). On multivariable analysis, lower sCD105 was associated with increased high-grade PC risk (ORper 1000 units=1.33, p=0.028). CONCLUSION Lower sCD105 levels were associated with intermediate and high-risk PC. Further investigation is warranted in a larger PC cohort. BACKGROUND/AIM Resistance to chemotherapeutic agents is the main cause of reduced survival in non-small cell lung cancer (NSCLC) patients. The Hedgehog (HH) pathway has been shown to be crucial in cell development and survival. Activated in several types of cancer it might be a potent bypass mechanism mediating chemotherapy resistance. MATERIALS AND METHODS HCC827 NSCLC cells were treated with sub-lethal doses of pemetrexed to produce pemetrexed resistance. RT-qPCR was performed to measure gene expression of HH pathway proteins. A cell growth assay was used to measure the impact of the HH-inhibitor Gant61 in naïve and chemoresistant cell lines. RESULTS Pemetrexed resistant cells showed significantly increased expression of HH signaling genes (GLI1, GLI2, GLI3, PTCH1, SHH). Supporting these results, pemetrexed resistant cells treated with the HH inhibitor Gant61 showed reduced proliferation compared to naïve cells. CONCLUSION HH pathway may play an important role in mediating pemetrexed resistance in NSCLC cells. Blocking the HH pathway may be a potential option to overcome this resistance. BACKGROUND/AIM Although numerous cytokines influence proliferation and progression of multiple myeloma (MM), a relevant action in the onset of the disease also seems to be played by the oxidative state. PATIENTS AND METHODS In the present study we evaluated the concentrations of interleukin-8 (IL-8) and soluble receptor of advanced glycation end products (sRAGE) in patients with MM, assessing the existing variations with respect to a control group and the possible existence of correlations between these molecules and the biological variables or the presence of a correlation between IL-8 and sRAGE. The study was conducted on 33 patients affected by MM compared to 39 healthy subjects. RESULTS IL-8 and sRAGE levels were significantly higher in MM patients compared to healthy subjects. sRAGE and IL-8 evidence no significant linear correlation. Furthermore, IL-8 was significantly increased in both sexes, but we found a slight variation for females compared to males. CONCLUSION IL-8 could play an important role in the onset of MM and the progression of bone disease, while the increased sRAGE values would seem to have a protective action in MM patients. Further studies on animal models may clarify the real impact of introducing modulation of IL-8 and sRAGE levels. BACKGROUND/AIM Polyamines are important for the growth of eukaryotic cells. At high levels, they promote proliferation, invasion and migration of tumour cells. Polyamine metabolism is an important new target for anticancer therapy. Some polyamine analogues can have an inhibitory effect on tumour cells. The aim of this study was to explore the potential of certain butylated derivatives of propanediamine for prostate cancer chemotherapy. MATERIALS AND METHODS Human prostate cancer cells, LNCaP, were used for the evaluation of the antiproliferative activity of polyamine analogs and their influence on spermine oxidase. RESULTS Tetrabutyl propanediamine and two new polyamine analogues inhibited the growth of LNCaP cells. At the same time, a strong activation of spermine oxidase was observed. CONCLUSION The investigated compounds demonstrated their potential value in the therapy of human prostate cancer. Their effect might be attributed to the activation of the polyamine catabolic pathway.