Musashi2 as a novel predictive biomarker for liver metastasis and poor prognosis in colorectal cancer

Abstract

Aberrant expression of musashi2 (MSI-2) has been detected in several malignancies. However, its role in the progression of colorectal cancer (CRC) remains unknown. Our study was designed to investigate the expression and prognostic significance of MSI-2 protein in patients with colorectal cancer. The expression of MSI-2 was detected in 164 patients' colorectal cancer and control specimens by the tissue microarray technique and immunohistochemical staining. The correlations between MSI-2 expression and clinicopathological variables including overall survival were analyzed. The prognostic value of liver metastasis is evaluated by logistic regression and receiver operating characteristic (ROC) analysis. MSI-2 was highly expressed in 32.9% (54/164) of the colorectal cancer. Overexpression of MSI-2 was associated with depth of invasion, lymph node metastasis, distant metastasis, liver metastasis, Tumor Node Metastasis (TNM) clinical stage, and Carcinoembryonicantigen (CEA) level (P = 0.040, 0.014, <0.001, <0.001, 0.003, and 0.002, respectively). In the Cox multivariate test, MSI-2 overexpression, lymph node metastasis, and distant metastasis were found to be the independent prognostic factors (P = 0.027, 0.010, and 0.001, respectively). Further logistic regression suggested that TNM stage and MSI-2 high expression were related to liver metastasis in colorectal cancer patients. Conclusively, our study indicates that MSI-2 overexpression is associated with an unfavorable prognosis and may be a potential biomarker for liver metastasis in colorectal cancer patients.

Our study indicates that MSI-2 overexpression is associated with an unfavorable prognosis and may be a potential biomarker for liver metastasis in colorectal cancer patients.

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Development and characterization of two human triple-negative breast cancer cell lines with highly tumorigenic and metastatic capabilities

Abstract

Triple-negative breast cancer (TNBC) is a group of cancer with high diversity, limited therapies, and poor prognosis. TNBC cell lines and animal models provide effective tools for studies and drug discovery. Here, we report the development of two TNBC cell lines (XtMCF and LmMCF) based on our existing cell model that consists of normal breast epithelial cell line MCF10F, estradiol-transformed cells trMCF, and Boyden chamber-selected tumorigenic cells bsMCF. The XtMCF and LmMCF cell line were derived from xenograft and lung metastasis of bsMCF cells, respectively. The bsMCF, XtMCF, and LmMCF cells have undergone epithelial–mesenchymal transition (EMT), exhibiting a mesenchymal-like feature. In vivo studies showed XtMCF and LmMCF cells were highly tumorigenic and metastatic. The injection of 5 × 10⁴ cells to CB17/SCID mice mammary fat pad produced xenografts in 9/9 mice and tumors reached 10 millimeters in diameter in 5 weeks. The injection of 1 × 10⁶ XtMCF or 8 × 10⁴ LmMCF cells into the mice tail vein was sufficient to form extensive lung metastases in 4 weeks. The two new cell lines exhibited CD44⁺/CD49f⁺ and CD44⁺/EpCAM⁺ cancer stem cell (CSC) characteristics, and the EGF-like domain of EpCAM was cleaved off. Together with the normal and early transformed counterparts, herein we provide a complete cancer model for the study of initiation, evolution, and identification of new therapeutics for TNBC. The finding that EGF-like domain of EpCAM was cleaved off in cells which have undergone EMT suggests this cleavage may be involved in the EMT process and the cancer stem cell properties of these cells.

The authors developed and characterized two highly tumorigenic and metastatic triple-negative breast cancer (TNBC) cell lines (XtMCF and LmMCF). The two new cell lines have undergone epithelial–mesenchymal transition (EMT), exhibiting a mesenchymal-like feature and CD44+/CD49f+ and CD44+/EpCAM+ cancer stem cell characteristics, and the EGF-like domain of EpCAM is cleaved off.

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Expression of aurora kinase A correlates with the Wnt-modulator RACGAP1 in gastric cancer

Abstract

Canonical Wnt signaling is involved in gastric carcinogenesis. The aim of this study was to identify the link between Wnt signaling and aurora kinase A (AURKA), a target for the treatment of gastrointestinal cancers. Publicly available microarray data were used to identify phenotype-specific protein–protein interaction (PPI) subnetworks. The in silico analysis revealed a gastric cancer-specific PPI subnetwork consisting of 2745 proteins and 50,935 interactions. We focused on the link of AURKA to a Wnt-specific interaction module consisting of 92 proteins. There was a direct association of AURKA with Rac GTPase-activating protein 1 (RACGAP1), as well as with CTNBB1 (β-catenin) and CDKN1A as second-order interactors. Differential expression analysis revealed a significant downregulation of both AURKA and RACGAP1 in gastric cancer compared to noncancer controls. Biopsies from a prospective cohort of 56 patients with gastric cancer (32 intestinal type, 24 diffuse type) and 20 noncancer controls were used for validation of the identified targets. The RT-PCR data confirmed a strong correlation of AURKA and RACGAP1 gene expression both in the tumor, the tumor-adjacent and the tumor-distant mucosa. RACGAP1 in the tumor was also associated with CTNBB1 expression, and inversely associated with CDKN1A gene expression. Immunohistochemistry confirmed expression of the RACGAP1 protein in gastric cancer and the tumor-adjacent mucosa. RACGAP1 expression was not associated with tumor stage, grading, Lauren type, Helicobacter pylori infection, or age. In conclusion, AURKA is directly associated with the expression of RACGAP1, a modulator of the canonical Wnt signaling pathway.

There is a close association between aurora kinase A (AURKA) and Rac GTPase-activating protein 1 (RACGAP1) gene expression in gastric cancer that could be confirmed in a prospective validation cohort. Key targets of Wnt signaling (β-catenin, p21) are second-order interactors connected to AURKA and RACGAP1. Expression of RACGAP1 does not seem to be related to tumor-specific factors such as Laurén type, tumor location, or differentiation of the tumor.

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Characterization of copy number alterations in a mouse model of fibrosis-associated hepatocellular carcinoma reveals concordance with human disease

Abstract

Hepatocellular carcinoma (HCC) is a prevalent human cancer with rising incidence worldwide. Human HCC is frequently associated with chronic liver inflammation and cirrhosis, pathophysiological processes that are a consequence of chronic viral infection, disturbances in metabolism, or exposure to chemical toxicants. To better characterize the pathogenesis of HCC, we used a human disease-relevant mouse model of fibrosis-associated hepatocarcinogenesis. In this model, marked liver tumor response caused by the promutagenic chemical N-nitrosodiethylamine in the presence of liver fibrosis was associated with epigenetic events indicative of genomic instability. Therefore, we hypothesized that DNA copy number alterations (CNAs), a feature of genomic instability and a common characteristic of cancer, are concordant between human HCC and mouse models of fibrosis-associated hepatocarcinogenesis. We evaluated DNA CNAs and changes in gene expression in the mouse liver (normal, tumor, and nontumor fibrotic tissues). Additionally, we compared our findings to DNA CNAs in human HCC cases (tumor and nontumor cirrhotic/fibrotic tissues) using publicly available data from The Cancer Genome Atlas (TCGA). We observed that while fibrotic liver tissue is largely devoid of DNA CNAs, highly frequently occurring DNA CNAs are found in mouse tumors, which is indicative of a profound increase in chromosomal instability in HCC. The cross-species gene-level comparison of CNAs identified shared regions of CNAs between human fibrosis- and cirrhosis-associated liver tumors and mouse fibrosis-associated HCC. Our results suggest that CNAs most commonly arise in neoplastic tissue rather than in fibrotic or cirrhotic liver, and demonstrate the utility of this mouse model in replicating the molecular features of human HCC.

This report demonstrates an accumulation of copy number alterations (CNAs) in liver tumors but not in surrounding preneoplastic liver tissue, in both human clinical samples and in a mouse model of fibrosis-associated hepatocellular carcinoma (HCC). These findings, together with previous results demonstrating increased epigenetic alterations indicative of genomic instability, suggest that chromosomal instability is a feature of tumor cells that precedes common mutations. Many of the segments with altered copy number, as well as the genes within those segments, were observed in liver tumors from both mice and humans, demonstrating the relevance of the mouse fibrosis-associated liver cancer model to human HCC.

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Nimotuzumab enhances temozolomide-induced growth suppression of glioma cells expressing mutant EGFR in vivo

Abstract

A mutant form of epidermal growth factor receptor (EGFR), EGFRvIII, is common in glioblastoma (GBM) and confers enhanced tumorigenic activity and drug resistance. Nimotuzumab, an anti-EGFR antibody, has shown preclinical and clinical activity to GBM, but its specific activity against EGFRvIII has not been fully investigated. Human glioma U87MG or LNZ308 cells overexpressing either wild-type (wt) EGFR or EGFRvIII were treated with nimotuzumab, temozolomide, or both. Expression and phosphorylation status of molecules were determined by Western blot analysis. Methylation status of promoter region of O⁶-methylguanine-DNA methyltransferase (MGMT) was detected by methylation-specific PCR. Antitumor activity was tested using nude mice bearing either subcutaneous or intracerebral xenografts along with analyses of EGFR phosphorylation status, proliferation, apoptosis, and vessel density. Nimotuzumab treatment resulted in reduction of EGFRvIII tyrosine phosphorylation with a decrease in Akt phosphorylation that was greater than that of wtEGFR. Correspondingly, antitumor effects, growth suppression and survival elongation, were more significant in mice bearing either subcutaneous or intracerebral tumor expressing EGFRvIII than in those expressing wtEGFR. These effects were markedly increased when temozolomide was combined with nimotuzumab. The post-treatment recurrent brain tumors exhibited a decrease in expression of the mismatch repair (MMR) proteins, MSH6 and MLH1, but their methylated MGMT status did not changed. Nimotuzumab has in vivo antitumor activity against GBM, especially those expressing EGFRvIII, when combined with temozolomide. This could provide a basis for preselection of patients with GBM by EGFR status who might benefit from the nimotuzumab and temozolomide combination therapy.

A mutant epidermal growth factor receptor (EGFR), EGFRvIII, is common in glioblastoma and confers aggressive tumorigenicity and drug resistance. This study demonstrates that nimotuzumab, an anti-EGFR antibody, enhanced the antitumor efficacy of temozolomide in glioma cells overexpressing EGFR, especially EGFRvIII, in vivo, suggesting that nimotuzumab and temozolomide combination is a potent and applicable strategy toward treatment of the devastating EGFRvIII-expressing glioblastoma.

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Triage of patients with AUS/FLUS on thyroid cytopathology: effectiveness of the multimodal diagnostic techniques

Abstract

The management of patients with thyroid cytopathologic diagnosis of atypia (or follicular lesion) of undetermined significance (AUS/FLUS) is a complex clinical problem. The purpose of this study was to develop a practical triage scheme based on multiple diagnostic tests in general use. We performed a retrospective cohort study involving 15,335 consecutive patients with a referral diagnosis of thyroid nodule between April 2011 and March 2015 using an institutional database. We obtained 904 patients with an initial cytopathologic diagnosis of AUS/FLUS who underwent repeat fine-needle aspiration or core needle biopsy, 388 of whom had a corresponding histopathological diagnosis for excised index lesions. The diagnostic performance of ultrasound (US) findings, repeat biopsy, and BRAF^V600E mutation in cytopathologic specimens were evaluated individually or as a set. Of the 388 resected AUS/FLUS cases, 338 (87.1%) were thyroid cancer. The positive likelihood ratios (LRs) for BRAF^V600E mutation and repeat biopsy result of suspicious for malignant cell (SMC) or worse were 11.6 (95% CI = 1.7–77.8) and 13.7 (95% CI = 4.6–41.0), respectively. The absence of suspicious findings on US combined with cytologic result of less than SMC or negative BRAF^V600E mutation produced negative LRs ranging from 0.06 to 0.15, corresponding to negative predictive values of over 90% in both primary and referral settings. For patients with AUS/FLUS cytopathology, clinical decision making can be guided by a simple triage scheme based on US findings, repeat biopsy, or BRAF^V600E mutation.

The management of an equivocal thyroid cytopathology test remains a complex clinical and public health problem. For patients with atypia (or follicular lesion) of undetermined significance (AUS/FLUS) cytopathology, clinical decision making can be guided by a simple triage scheme based on US findings, repeat biopsy, or BRAFV600E mutation.

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A systematic review and meta-analysis of prescribing practices of antidepressants in cancer patients

Abstract

Background

Antidepressants are commonly used for the pharmacological treatment of depression. We aimed to summarise the prevalence of antidepressant prescription to cancer patients, and differences by study or patient characteristics.

Methods

PubMed, Embase, Web of Science, Scopus and psychINFO were searched using keywords 'psychotropic', 'antidepressants', 'prescription' and 'cancer'. Prevalence of antidepressants, type, dose and follow-up of antidepressants and prescriber details were extracted.

Results

Overall, 1537 articles between 1979 and February 2015 were found, 38 met the inclusion criteria and were reviewed according to PRISMA guidelines. The prevalence rate of prescribing antidepressants to cancer patients was 15.6% (95% CI = 13.3–18.3). Prescription was significantly less common in studies from Asia (7.4%; 95% CI = 4.3–12.5), more common in female (22.6%; 95% CI = 16.0–31.0) or breast cancer patients (22.6%; 95% CI = 16.0–30.9). Selective serotonin reuptake inhibitors were the most frequently prescribed antidepressants. General practitioners and psychiatrists, followed by oncologists, were identified as the major providers of antidepressant prescriptions to cancer patients. Few studies reported the exact dose, length of time drugs were prescribed for or follow-up regimens.

Conclusions

There is considerable variation in the prescribing patterns of antidepressants across the world, with few studies reporting robust data on exact dose or follow-up regimens. Prospective studies that monitor antidepressant prescribing, including details of reasons for prescribing and the healthcare providers involved, dose, change in dose or type of medication and follow-up are needed to ascertain whether patients are being treated optimally and if side effects or drug–drug interactions are identified and managed. Copyright © 2016 John Wiley & Sons, Ltd.

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How doctors communicate the initial diagnosis of cancer matters: cancer disclosure and its relationship with Patients' hope and trust

Abstract

Objective

The study is to examine the relationships between perceived initial cancer disclosure communication with doctors, levels of hope, and levels of trust in doctors among cancer patients in China.

Methods

A total number of 192 cancer inpatients in a cancer hospital in China were surveyed. Perceived disclosure strategies, levels of hope, levels of trust in their doctors, as well as the demographic information were obtained from the participants.

Results

In addition to age, patients who had higher levels of perceived emotional support from doctors, or higher levels of perceived personalized disclosure from doctors, or higher levels of perceived discussion of multiple treatment plans with doctors were more likely to have higher levels of trust in doctors. In addition to perceived health status, perceived emotional support from doctors significantly predicted participants' levels of hope. That is, patients who had higher higher levels of perceived doctors' emotional support were more likely to have higher levels of hope. Key disclosure person was a marginally significant variable, that is, patients who were mainly disclosed by family members might have higher levels of hope compared with patients who were mainly disclosed by doctors.

Conclusions

When communicating with a cancer patient, doctors might not ignore the importance of emotional support during cancer diagnosis communication. Doctors might want to involve family and collaborate with family to find out ways of personalized disclosure. During the communication process, doctors could provide their patients with multiple treatment options and discuss the benefits and side effects of each treatment. Copyright © 2016 John Wiley & Sons, Ltd.

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p53 Reactivation by PRIMA-1Met (APR-246) sensitises V600E/KBRAF melanoma to vemurafenib

Publication date: March 2016
Source:European Journal of Cancer, Volume 55
Author(s): Mohammad Krayem, Fabrice Journe, Murielle Wiedig, Renato Morandini, Ahmad Najem, François Salès, Leon C. van Kempen, Catherine Sibille, Ahmad Awada, Jean-Christophe Marine, Ghanem Ghanem
Intrinsic and acquired resistance of metastatic melanoma to ^V600E/KBRAF and/or MEK inhibitors, which is often caused by activation of the PI3K/AKT survival pathway, represents a major clinical challenge. Given that p53 is capable of antagonising PI3K/AKT activation we hypothesised that pharmacological restoration of p53 activity may increase the sensitivity of BRAF-mutant melanoma to MAPK-targeted therapy and eventually delay and/or prevent acquisition of drug resistance. To test this possibility we exposed a panel of vemurafenib-sensitive and resistant (innate and acquired) ^V600E/KBRAF melanomas to a ^V600E/KBRAF inhibitor (vemurafenib) alone or in combination with a direct p53 activator (PRIMA-1^Met/APR-246). Strikingly, PRIMA-1^Met synergised with vemurafenib to induce apoptosis and suppress proliferation of ^V600E/KBRAF melanoma cells in vitro and to inhibit tumour growth in vivo. Importantly, this drug combination decreased the viability of both vemurafenib-sensitive and resistant melanoma cells irrespectively of the TP53 status. Notably, p53 reactivation was invariably accompanied by PI3K/AKT pathway inhibition, the activity of which was found as a dominant resistance mechanism to BRAF inhibition in our lines. From all various combinatorial modalities tested, targeting the MAPK and PI3K signalling pathways through p53 reactivation or not, the PRIMA-1^Met/vemurafenib combination was the most cytotoxic. We conclude that PRIMA-1^Met through its ability to directly reactivate p53 regardless of the mechanism causing its deactivation, and thereby dampen PI3K signalling, sensitises ^V600E/KBRAF-positive melanoma to BRAF inhibitors.



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Long term follow up of the EORTC 18952 trial of adjuvant therapy in resected stage IIB–III cutaneous melanoma patients comparing intermediate doses of interferon-alpha-2b (IFN) with observation: Ulceration of primary is key determinant for IFN-sensitivity

Publication date: March 2016
Source:European Journal of Cancer, Volume 55
Author(s): Alexander M.M. Eggermont, Stefan Suciu, Piotr Rutkowski, Willem H. Kruit, Cornelis J. Punt, Reinhard Dummer, François Salès, Ulrich Keilholz, Gaetan de Schaetzen, Alessandro Testori
BackgroundWe report on the long term outcome of the EORTC 18952 adjuvant interferon (IFN) trial in 1388 resected stage IIB/III melanoma patients and identify key predictive factors for outcome.MethodsWe analysed outcome of the EORTC 18952 trial (4 weeks of IFN, 10 MU, 5 times/week for 4 weeks followed by 12 months IFN at 10 MU, 3 times/week versus followed by 24 months IFN at 5 MU 3 times/week versus observation) regarding relapse-free survival (RFS), distant metastasis-free interval/survival (DMFI/DMFS), and overall survival (OS), and analysed potential predictive factors of outcome.FindingsAt a median follow-up of 11 years, the comparison of IFN 13 months versus IFN 25 months versus observation yielded estimated hazard ratios (HR) for RFS of 0.94 versus 0.84 (p = 0.06); for DMFI 0.95 versus 0.82 (p = 0.027); for DMFS 0.95 versus 0.84 (p = 0.07); and for OS 0·95 versus 0.84 (p = 0.08), respectively. The impact of treatment was greatest in the ulceration group, whereas in patients with non-ulcerated primaries the impact was null (HR ≥ 1.0). In patients with ulcerated melanoma the HR for IFN 13 months versus 25 months versus observation were for: RFS 0.82 (p = 0.16) versus 0.61 (p = 0.0008); DMFS 0.76 (p = 0.06) versus 0.57 (p = 0.0003); OS 0.80 (p = 0.13) versus 0.59 (p = 0.0007). In stage IIB/III-N1 (microscopic nodal involvement only) patients with ulcerated melanoma the HR estimates were for: RFS 0.85 versus 0.62; DMFS 0.80 versus 0.56; OS 0.77 versus 0.54.ConclusionsThis long term report of the EORTC 18952 trial demonstrates the superiority of the 25-month IFN schedule and defines ulceration of the primary as the overriding predictive factor for IFN-sensitivity.



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Lycopene acts through inhibition of IκB kinase to suppress NF-κB signaling in human prostate and breast cancer cells

Abstract

We studied the effect of the potent dietary antioxidant lycopene on multiple points along the nuclear factor kappa B (NF-κB) signaling pathway in prostate and breast cancer cells. Lycopene significantly inhibited prostate and breast cancer cell growth at physiologically relevant concentrations of ≥1.25 μM. Similar concentrations also caused a 30–40 % reduction in inhibitor of kappa B (IκB) phosphorylation in the cells, as determined by western blotting. Furthermore, the same degree of inhibition by lycopene was observed for NF-κB transcriptional activity, as determined by reporter gene assay. Concomitant with this, immunofluorescence staining of lycopene-treated cells showed a significant suppression (≥25 %) of TNF-induced NF-κB p65 subunit nuclear translocation. Further probing of lycopene's effects on upstream elements of the NF-κB pathway showed a 25 % inhibition of both activity of recombinant IκB kinase β (IKKβ) kinase in a cell-free in vitro assay, as well as activity of IKKβ immunoprecipitated from MDA-MB-231 cells treated with lycopene. In conclusion, the anticancer properties of lycopene may occur through inhibition of the NF-κB signaling pathway, beginning at the early stage of cytoplasmic IKK kinase activity, which then leads to reduced NF-κB-responsive gene regulation. Furthermore, these effects in cancer cells were observed at concentrations of lycopene that are relevant and achievable in vivo.

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Low expression of fibulin-1 correlates with unfavorable prognosis in gastric cancer

Abstract

The tumor-suppressing role of fibulin-1 has been described in several types of cancers. However, the expression and role of fibulin-1 in the development and progression of gastric cancer (GC) remain largely unknown. In this study, RT-PCR and immunochemistry were used to detect the fibulin-1 expression in GC samples. We have found that the fibulin-1 protein and mRNA levels were downregulated in GC. When investigating the correlation between fibulin-1 expression and clinicopathological characteristics, we have found that low fibulin-1 protein expression was associated with poor tumor differentiation and advanced N stage. Low fibulin-1 protein expression was also an independent prognostic factor for patient survival. To clarify the reason of fibulin-1 downregulation in GC, the mRNA expression and methylation status of fibulin-1 were examined in GC fresh tissue samples (n = 36). We found that the transcriptional expression of fibulin-1 was negatively associated with fibulin-1 promoter hypermethylation, and fibulin-1 hypermethylation was associated with Helicobacter pylori infection. Finally, the effects of fibulin-1 overexpression on cell proliferation and apoptosis were examined. We have found that fibulin-1 overexpression suppressed the growth of GC both in vitro and in vivo and induced apoptosis by increasing cleaved caspase-3 expression. In conclusion, fibulin-1 acts as a tumor suppressor gene, is frequently hypermethylated in GC, and can potentially serve as a useful biomarker for patient prognosis.

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Are SMAD7 rs4939827 and CHI3L1 rs4950928 polymorphisms associated with colorectal cancer in Egyptian patients?

Abstract

A wide variety of genes have been associated with colorectal cancer (CRC) development and progression. The SMAD7 gene encodes an intracellular protein, which inhibits the transforming growth factor beta (TGF-β) signaling pathway, thereby having a key role in the control of neoplastic processes in various organs. The CHI3L1 gene encodes glycoprotein YKL-40, which plays a role in cell proliferation, anti-apoptosis, and angiogenesis. The present study aimed to evaluate the association of single nucleotide polymorphisms (SNPs) SMAD7 rs4939827 and CHI3L1 rs4950928, as well as circulating TGFβ-1 and YKL-40 levels with CRC in an Egyptian population of 77 CRC patients and 36 healthy controls. Polymorphisms in the SMAD7 rs4939827 and the CHI3L1 rs4950928 genes were determined using the real-time polymerase chain reaction (RT-PCR). Both the SMAD7 rs4939827 TT genotype and the CHI3L1 rs4950928 C allele were associated with the rectal but not the colon cancer. In addition, the C allele of both SMAD7 rs4939827 and CHI3L1 rs4950928 was associated with increased serum levels of TGF-β1 and YKL-40, respectively. In conclusion, our data suggest that SMAD7 rs4939827 and CHI3L1 rs4950928 SNPs have no significant association with CRC. A significant association of SNP in SMAD7 rs4939827 and CHI3L1 rs4950928 was revealed between the rectal cancer and colon cancer patients.

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Dronabinol has preferential antileukemic activity in acute lymphoblastic and myeloid leukemia with lymphoid differentiation patterns

Abstract

Background

It has been previously demonstrated in several cancer models, that Dronabinol (THC) may have anti-tumor activity – however, controversial data exists for acute leukemia. We have anecdotal evidence that THC may have contributed to disease control in a patient with acute undifferentiated leukemia.

Methods

To test this hypothesis, we evaluated the antileukemic efficacy of THC in several leukemia cell lines and native leukemia blasts cultured ex vivo. Expression analysis for the CB1/2 receptors was performed by Western immunoblotting and flow cytometry. CB-receptor antagonists as well as a CRISPR double nickase knockdown approach were used to evaluate for receptor specificity of the observed proapoptotic effects.

Results

Meaningful antiproliferative as well as proapoptotic effects were demonstrated in a subset of cases – with a preference of leukemia cells from the lymphatic lineage or acute myeloid leukemia cells expressing lymphatic markers. Induction of apoptosis was mediated via CB1 as well as CB2, and expression of CB receptors was a prerequisite for therapy response in our models. Importantly, we demonstrate that antileukemic concentrations are achievable in vivo.

Conclusion

Our study provides rigorous data to support clinical evaluation of THC as a low-toxic therapy option in a well defined subset of acute leukemia patients.

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