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Development of a new knock-in mouse model and evaluation of pharmacological activities of lusutrombopag, a novel, non-peptidyl small-molecule agonist of human thrombopoietin receptor, c-mpl

Thrombocytopenia results from a decrease in platelets due to either increased platelet destruction and/or inadequate platelet production. This is a common problem in the management of patients with cancer and other conditions that affect hematopoietic cells including myelodysplastic syndrome, idiopathic thrombocytopenic purpura (ITP), chronic liver disease, and acquired immunodeficiency syndrome [1-7]. Thrombopoietin (TPO) increases platelet production through stimulation of proliferation and differentiation of megakaryocytic progenitor cells and induction of megakaryocyte maturation [8].
Source: Experimental Hematology - Category: Hematology Authors: Source Type: research

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Immunotherapy is a promising method of treatment for a number of cancers. Many of the curative results have been seen specifically in advanced-stage melanoma. Despite this, single-agent therapies are only successful in a small percentage of patients, and relapse is very common. As chemotherapy is becoming a thing of the past for treatment of melanoma, the combination of cellular therapies with immunotherapies appears to be on the rise in in-vivo models and in clinical trials. These forms of therapies include tumor-infiltrating lymphocytes, T-cell receptor, or chimeric antigen receptor-modified T cells, cytokines [interleuk...
Source: Melanoma Research - Category: Cancer & Oncology Tags: Review Article Source Type: research
In this study, we investigated TRAF3IP3 tumorigenic function. TRAF3IP3 protein was present in several cancer cell lines, with highest levels in melanoma. In addition, tumor microarray analysis on 23 primary melanoma and nine positive lymph nodes revealed that 70% of human primary melanoma and 66% of lymph node metastases were positive for TRAF3IP3. Importantly, TRAF3IP3 downregulation correlated with an 83% reduction of tumor growth in a subcutaneous xenograft mouse model (n=10, P=0.005). Immunohistochemistry analysis of the tumors revealed that TRAF3IP3-shRNA tumors had increased apoptosis (n=4, P
Source: Melanoma Research - Category: Cancer & Oncology Tags: ORIGINAL ARTICLES: Basic research Source Type: research
The aim of this study was to assess the prognostic importance of lymph node ratio (LNR) in stage III melanoma after complete lymph nodal dissections. From European Organization for Research and Treatment of Cancer randomized trials 18871, 18952, and 18991, 2358 patients had full information on positive and examined lymph nodes (LNs) and were included. Cox proportional hazards models stratified by trial were used to assess the prognostic impact of LNR adjusted for confounders on melanoma-specific survival. Optimal cutoff values for LNR were calculated for each LN dissection site (axillary, inguinal, and neck). LNR (≥ vs.
Source: Melanoma Research - Category: Cancer & Oncology Tags: ORIGINAL ARTICLES: Clinical research Source Type: research
The development of cancer immunotherapy and targeted therapy has reached an important inflection point in the history of melanoma. Immune checkpoint inhibitors and kinase inhibitors are today’s standard of care treatments in advanced melanoma patients. Treatment-related toxicities can be very intriguing and quite challenging. Sarcoidosis is a multisystemic granulomatous disease characterized by an aberrant immune response to unknown antigens, whereas sarcoid-like reactions (SLRs) refer to localized clinical features. We carried out a single-center observational study in patients with stage IIB–IV melanoma treat...
Source: Melanoma Research - Category: Cancer & Oncology Tags: ORIGINAL ARTICLES: Clinical research Source Type: research
Desmoplastic melanomas (DM) have unique and challenging clinical presentations and histomorphology. A characteristic feature is the presence of scattered lymphoid aggregates. However, the nature of these aggregates is not defined. We hypothesized that they may be tertiary lymphoid structures (TLS), and may be associated with programmed death ligand 1 (PD-L1) expression. We searched our tissue database for ‘pure’ DMs and for scars as control tissues, collected clinical information, and reviewed H&E histology. We performed multispectral imaging after staining for CD8, CD20, PNAd, FoxP3, CD83, and Ki67, and assess...
Source: Melanoma Research - Category: Cancer & Oncology Tags: ORIGINAL ARTICLES: Clinical research Source Type: research
In this study, we show that in an area with low melanoma incidence, CDKN2A germline mutations in patients with melanoma and personal or family history of pancreatic cancer are mainly present in the setting of familial or multiple melanoma cases. In addition, a relatively young age (≤52 years) at pancreatic diagnosis is an additional single criterion that might also be considered.
Source: Melanoma Research - Category: Cancer & Oncology Tags: Short Communications Source Type: research
AbstractPurposeThe aims of this retrospective analysis were to compare68Ga-PSMA PET findings and low-dose CT findings (120  kV, 30 mA), and to obtain semiquantitative and quantitative68Ga-PSMA PET data in patients with prostate cancer (PC) bone metastases.MethodsIn total, 152 PET/CT scans from 140 patients were evaluated. Of these patients, 30 had previously untreated primary PC, and 110 had biochemical relapse after treatment of primary PC. All patients underwent dynamic PET/CT scanning of the pelvis and lower abdomen as well as whole-body PET/CT with68Ga-PSMA-11. The PET/CT scans were analysed qualitatively (vi...
Source: European Journal of Nuclear Medicine and Molecular Imaging - Category: Nuclear Medicine Source Type: research
Conclusions99mTc-maraciclatide accumulates in PCa bone metastases in keeping with increased αvβ3 integrin expression. Greater activity in metastases with lower CT density suggests that uptake is related to osteoclast activity. Changes in planar and SPECT T:M ratios after 12  weeks of treatment differed between patients with and without PD and99mTc-maraciclatide imaging may be a potential method for assessing early response.
Source: European Journal of Nuclear Medicine and Molecular Imaging - Category: Nuclear Medicine Source Type: research
Source: European Journal of Nuclear Medicine and Molecular Imaging - Category: Nuclear Medicine Source Type: research
AbstractPurposePrevious studies in prostate cancer (PCa) patients tried to correlate the onset of local recurrence (LR) with the development of distant metastases and formulated, based on theoretical and experimental data, hypotheses linking the two events. We aimed to address this issue with11C-choline positron emission tomography/computed tomography (PET/CT).MethodsThis retrospective study included 491 PCa patients previously treated with radical prostatectomy who had undergone11C-choline PET/CT owing to biochemical failure. Further inclusion criteria were availability of clinical and pathological variables for survival ...
Source: European Journal of Nuclear Medicine and Molecular Imaging - Category: Nuclear Medicine Source Type: research
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