Case Report: GcMAF Treatment in a Patient with Multiple Sclerosis

Background/Aim: Gc protein-derived macrophage-activating factor (GcMAF) has various functions as an immune modulator, such as macrophage activation, anti-angiogenic activity and anti-tumor activity. Clinical trials of second-generation GcMAF demonstrated remarkable clinical effects in several types of cancers. Thus, GcMAF-based immunotherapy has a wide application for use in the treatment of many diseases via macrophage activation that can be used as a supportive therapy. Multiple sclerosis (MS) is considered to be an autoimmune disorder that affects the myelinated axons in the central nervous system (CNS). This study was undertaken to examine the effects of second-generation GcMAF in a patient with MS. Results: This case study demonstrated that treatments of GcMAF in a patient with MS have potent therapeutic actions with early beneficial responses, especially improvement of motor dysfunction. Conclusion: GcMAF shows therapeutic potency in the treatment of MS.

from Cancer via ola Kala on Inoreader http://ift.tt/295ECWN
via IFTTT

Case Report: A Non-small Cell Lung Cancer Patient Treated with GcMAF, Sonodynamic Therapy and Tumor Treating Fields

Background/Aim: Macrophage activating factor (MAF)-based immunotherapy has a wide application for use in treating many diseases via macrophage activation. Sonodynamic therapy (SDT) using low-intensity ultrasound and tumor treating field (TTF) therapy are novel therapeutic modalities. SDT is usually combined with ozone therapy to improve local hypoxia within the tumor environment. Case Report: We treated a 77-year-old male diagnosed with non-small cell lung cancer ((NSCLC) stage 3B) using second-generation serum GcMAF and oral colostrum MAF-based immunotherapy combined with SDT, TTF and ozone therapies. Results: This case report demonstrates that GcMAF, oral colostrum MAF, SDT, TTF and ozone therapy can be used for NSCLC without adverse effects. Conclusion: This case report suggests a new concept of cancer treatment using local destruction of cancer tissue, in this case conducted with SDT and TTF therapy, to be used in combination with serum GcMAF and colostrum MAF immunotherapy as a systemic treatment.

from Cancer via ola Kala on Inoreader http://ift.tt/28YLJfZ
via IFTTT

Current State of and Problems Related to Cancer of the Intestinal Tract Associated with Crohn's Disease in Japan

Background/Aim: Cancer of the intestinal tract (small and large intestine) associated with Crohn's disease has a low incidence but can be fatal if it develops. Thus, the key question is how to deal with this type of cancer. The current study surveyed major medical facilities that treat inflammatory bowel disease (IBD) surgically in Japan in order to examine the clinical features of cancer of the intestinal tract associated with Crohn's disease and explore ways to deal with this cancer in the future. Patients and Methods: Sixteen major medical facilities that treat IBD surgically were surveyed regarding cancer of the intestinal tract associated with Crohn's disease. The medical facilities had treated 3,454 patients with Crohn's disease, 122 of whom had developed intestinal cancer. The medical facilities were surveyed regarding those 122 patients. Results: The incidence of intestinal cancer associated with Crohn's disease has increased yearly. Cancer most often developed in the left side of the colon and, particularly, in the rectum and anal canal. Seventy-six percent of cases were diagnosed preoperatively, 4% were diagnosed intraoperatively, while the remaining 20% were diagnosed pathologically after surgery. The most prevalent histological type of cancer was mucinous carcinoma (50%). Forty-two percent of cancers were differentiated, with 4% being poorly differentiated. The surgical procedure performed most often (67%) was abdominoperineal resection. The 5-year survival rate by stage was 88% for Stage I, 68% for Stage II, 71% for Stage IIIa, 25% for Stage IIIb and 0% for Stage IV. Overall, the 5-year survival rate was 52%. Conclusion: Gastrointestinal (GI) cancer associated with Crohn's disease had an incidence of 3.5%, but also involved a poor prognosis with a 5-year survival rate of 52%. Early detection through surveillance is crucial to improving the prognosis for patients. However, surveillance of the intestinal tract with endoscopy or contrast studies is technically and diagnostically hampered by Crohn's disease and intestinal strictures. A biopsy of the anal canal, a common site of cancer, can readily be performed and constitutes the first step in surveillance.

from Cancer via ola Kala on Inoreader http://ift.tt/295EtT8
via IFTTT

Safety of Emulsifying Lipid Formulation Containing Omega-3 Polyunsaturated Fatty Acids for Patients with Crohn's Disease

Background/Aim: The efficacy of omega-3 supplementation by oral capsule for patients with Crohn's disease (CD) remains controversial. We investigated the safety and efficacy of an omega-3 emulsified formulation. Patients and Methods: Six patients with CD in remission participated in this open-label clinical trial. Patients ingested one bottle (100 ml) of the test formulation (IMARK S®) daily for 28 days. After a 1-month washout period, patients ingested two bottles of the formulation daily for 28 days. Anthropometric and blood tests were performed before and after each intervention. Results: The omega-3 emulsifying formulation was safe with minimal side-effects. Body weight and body-mass index were not altered; however, CD activity index scores tended to decrease after ingested one bottle of formulation. Blood tests revealed no severe adverse effects. Conclusion: Supplementation with an omega-3 emulsifying formulation can be safe and useful for maintaining remission in patients with CD and warrants further studies.

from Cancer via ola Kala on Inoreader http://ift.tt/28YLKk4
via IFTTT

Clinical Effects of Orally Administered Lipopolysaccharide Derived from Pantoea agglomerans on Malignant Tumors

Background/Aim: It has been reported that oral administration of lipopolysaccharide (LPS) recovers an individual's immune condition and induces the exclusion of foreign matter, inflammation and tissue repair. We orally administered LPS from the wheat symbiotic bacteria Pantoea agglomerans, which has been ingested and proven to be safe, to cancer patients. Our observation of clinical improvements resulting from this treatment are reported. Patients and Methods: Sixteen cancer patients who exhibited declined small intestinal immune competence were treated between June and September, 2015. Diagnosis was based on our evaluation on small intestinal immune competence and macrophage activity. Results: The state of malignant tumors at 3 months after starting this treatment was complete recovery for 3 cases, remission for 7 cases, maintenance for 4 cases, exacerbation for 1 case and death for 1 case (total response rate=62.5%). Small intestinal immune competence and macrophage activity recovered in all cases, suggesting that oral administration of LPS contributes to disease improvement. No clear side-effects that appeared to be related to LPS intake were noted. Conclusion: Intake of an appropriate level of Pantoea agglomerans LPS recovers small intestinal immune competence and macrophage activity, contributing to improvement of malignant tumors' therapy.

from Cancer via ola Kala on Inoreader http://ift.tt/295EsPh
via IFTTT

Adoptive Chemoimmunotherapy Using Activated {alpha}{beta} T Cells for Stage IV Colorectal Cancer

Background/Aim: Adoptive immunotherapy of cancer is evolving with the development of novel technologies that generate proliferation of large numbers of αβ and T cells. We evaluated the safety and efficacy of the combination of adoptive immunotherapy using αβ T cells with chemotherapy for stage IV colorectal cancer (CRC). Patients and Methods: Fifteen patients with advanced or recurrent CRC received XELOX + bevacizumab + ex vivo expanded αβ T lymphocytes as a first-line chemoimmunotherapy. Results: Median age of the 15 patients (4 men, 11 women) was 65 years (range=49-80). Median progression-free survival was 21.3 months. Response rate was 80% (complete response (CR)=26.7%, partial response (PR)=53.3%, stable disease (SD)=20% and progressive disease (PD)=0%). Most adverse events were mild to moderate regarding their intensity and immunotherapy-associated toxicity was minimal. Conclusion: Combination of adoptive αβ T cell immunotherapy with chemotherapy for stage IV CRC is feasible and safe.

from Cancer via ola Kala on Inoreader http://ift.tt/28YLEZC
via IFTTT

Retrospective Analysis of Growth Speed of 54 Lesions of Colitis-associated Colorectal Neoplasia

Aim: This study used a multicenter questionnaire survey to evaluate the morphology and progression of the initial lesion in cases of colitis-associated colorectal neoplasia (CRN). Patients and Methods: Endoscopic images of lesions that had been definitively diagnosed as CRN by pathological examination were retrospectively reviewed. Results: This resulted in the identification of 54 initial lesions in 49 patients. The 54 initial lesions fell into the following categories: 22 endoscopically visible localized lesions consisting of 18 elevated lesions and 4 depressed lesions, as well as 32 lesions that were not endoscopically visible as localized and consisted of 20 active-phase mucosal lesions and 12 remission-phase mucosal lesions. Nineteen of the lesions eventually became advanced cancers, while 35 lesions eventually became early-stage cancers. The final lesions were 40 elevated lesions, 5 flat or depressed lesions and 9 stenotic lesions. The form of growth of the advanced cancers was progressive stenosis or increased elevation. For approximately 69% of the early-stage cancers, the growth form was increasing elevation or development of elevation. For 73.6% of the advanced cancers, the initial lesion underwent rapid growth and became advanced cancer within 3 years; they accounted for 25.9% of the total cancers. Approximately 40% of the initial lesions of CRN were endoscopically visible as localized lesions, while approximately 60% were judged to be inflammatory mucosal lesions. Conclusion: It will be necessary to proactively take biopsy inflammatory mucosal lesions in order to discover tumors early and periodic surveillance should be performed with the knowledge that tumors may grow very quickly.

from Cancer via ola Kala on Inoreader http://ift.tt/295Ex5z
via IFTTT

Safety and Anti-tumor Effects of Docetaxel Plus Cisplatin in Intermediate- and High-risk Endometrial Cancer

Background: Endometrial cancer (EC) has a poor prognosis due to drug resistance. Patients and Methods: We evaluated the safety and efficacy of adjuvant combination chemotherapy with docetaxel plus cisplatin ((DP) docetaxel, 70 mg/m²; cisplatin, 60 mg/m²; every 28 days) in EC patients at intermediate-risk (IR) or high-risk (HR) for recurrence. Results: Sixty-four patients diagnosed with EC were enrolled. Stage-I, -II, -III and -IV disease was noted in 23, 7, 28 and 6 patients, respectively. Histopathological analyses revealed that 56, 3, 1 and 4 patients had endometrioid, serous, clear-cell or "other" types of carcinoma. Grade-3/4 hematologic toxicities were found at 80% and 95% in patients in IR and HR groups, respectively. In IR and HR groups, mean progression-free (PFS) survival was 69.5 and 29.5, while overall survival (OS) was 59.6 and 47.5 months, respectively. Conclusion: DP may be clinically safe and useful treatment for EC.

from Cancer via ola Kala on Inoreader http://ift.tt/28YLv8F
via IFTTT

Immunohistochemical Analysis of WT1 Antigen Expression in Various Solid Cancer Cells

For a peptide-pulsed dendritic cell (DC) vaccine to work effectively in cancer treatment, it is significant that the target protein is expressed in cancer cells. Wilms' tumor 1 (WT1) has been identified as a molecular target for immune cell therapy of cancer. We evaluated the protein expression levels of WT1 in various solid tumors, as well as mucin 1 (MUC1) or major histocompatibility complex (MHC) class l molecules. Seven hundred and thirty-eight patients whose tissue samples were examined by immunohistochemical analysis agreed to undergo DC vaccine therapy. The positive staining of WT1 in tumor cells was observed in 25.3% of patients, with only 8.5% of them showing moderate to strong expression; moreover, WT1 tended to localize in the nucleus and cytoplasm. A positive staining of tumor cells by an anti-MHC class l monoclonal antibody was observed in 98.6% and by an anti-MUC1 monoclonal antibody in 76.8% of the patients. In relation to the application of cancer-specific immunotherapy, these findings provide useful information for determining the efficacy of MUC1- and WT1-targeted therapy.

from Cancer via ola Kala on Inoreader http://ift.tt/295ExSV
via IFTTT

Global Liver Gene Expression Analysis on a Murine Metabolic Syndrome Model Treated by Low-molecular-weight Lychee Fruit Polyphenol (Oligonol(R))

Background/Aim: Oligonol® (OLG) is a low-molecular-weight lychee fruit polyphenol mainly containing catechin-type monomers and oligomers of proanthocyanidins. Dietary OLG supplementation reportedly improves lipid metabolism disorder and lowers the visceral fat level in animal and human studies. Thus, we investigated the mechanism behind the protective and beneficial effects of OLG on a Western diet (WD)-induced metabolic syndrome (MetS) of a murine model. Materials and Methods: Using the C57BL/6J mouse for the MetS model, mice were divided into three groups: control (normal diet: ND), Western diet (WD) and WD + 0.5% OLG (OLG) groups. The WD group was fed a high-calorie (high fructose plus high fat) diet for 12 weeks to develop MetS. At week 12, all mice were sacrificed and the blood and liver were obtained for histological and biological examinations and RNA sequencing (RNA-Seq). Results: Body weight, liver weight, plasma triglycerides (TG), total cholesterol (T-Cho) and alanine aminotransferase (ATS) levels of both OLG groups were significantly lower than those of the WD group. On histological examination of the liver, the area of fatty deposits was shown to be suppressed by OLG administration. Expression gene analysis in the liver of WD- versus OLG-fed mice by RNA-Seq showed that 464/45,706 genes exhibited a significant change of expression (corrected p-value <0.05, absolute value of fold change (FC) ≥2). Gene network analysis showed that genes related to hepatic steatosis, liver inflammation and tumor invasion were inactivated in the OLG group. In particular, the lipid metabolism-related genes Lpin1, Adig and Cidea were regulated by OLG administration. Conclusion: OLG may function to suppress MetS and the progression of geriatric diseases in WD-fed mice by regulating the expression of lipid metabolism, inflammation and tumor-related genes in the liver.

from Cancer via ola Kala on Inoreader http://ift.tt/28YM2r3
via IFTTT

Gene Expression in Lipopolysaccharide-treated Human Monocytes Following Interaction with Hepatic Cancer Cells

Background/Aim: Monocytes migrate into the tissue where they differentiate into various types of macrophages with tissue-specific characteristics. When human monocytes are co-cultured with colon cancer cells they exhibit increased mRNA expression of angiogenesis- and signaling pathway-related genes; however, this increase is suppressed by pretreatment with low-dose lipopolysaccharide (LPS). Thus, LPS-treated human monocytes may be useful in suppressing tumor invasion and proliferation in colon cancer. However, it is suggested that the characteristics of tumor-associated macrophages may differ depending on the type of cancer. The function of human tumor-associated macrophages in hepatic cancer remains unclear. In this study, we investigated mRNA expression of various genes in LPS-treated human monocytes following interaction with hepatic cancer cells. Materials and Methods: The human monocyte cell line THP-1 was treated with LPS and subsequently co-cultured with the human hepatic cancer cell line HepG2. mRNA expression of various factors were then analyzed using quantitative real-time polymerase chain reaction (PCR) and DNA microarray. Results: The mRNA expressions of monocyte chemotactic protein-1, vascular endothelial growth factor-A, tumor necrosis factor-α, interleukin (IL)-1β, IL-8, nuclear factor-B, RelB, signal transducer and activator of transcription 3, IL-10 and transforming growth factor-β in THP-1 cells following interaction with HepG2 cells, were suppressed by pretreatment with LPS. Conclusion: LPS-treated human monocytes may be useful in suppressing tumor invasion and proliferation of hepatic cancer, as well as colon cancer. The co-culture system of monocytes and cancer cells may be beneficial for evaluating antitumor effects in LPS-treated monocytes.

from Cancer via ola Kala on Inoreader http://ift.tt/295ECG9
via IFTTT

Effect of Lipopolysaccharide Derived from Pantoea agglomerans on the Phagocytic Activity of Amyloid {beta} by Primary Murine Microglial Cells

Background/Aim: Monophosphoryl lipid A, lipopolysaccharide (LPS)-derived Toll-like receptor (TLR) 4 agonist, has been shown to be effective in the prevention of Alzheimer's disease (AD) by enhancing phagocytosis of amyloid β (Aβ) by brain microglia. Our recent study demonstrated that oral administration of LPS derived from Pantoea agglomerans (LPSp) activates peritoneal macrophages and enhances the phagocytic activity via TLR4 signaling pathway; however, the effect of LPSp on Aβ phagocytosis in microglia is still unknown. Materials and Methods: Primary microglial cells were isolated from adult mouse brain by enzymatic digestion, following myelin removal and magnetic separation of cluster of differentiation (CD) 11b. Phagocytic analysis of the primary microglia was measured by using HiLyte™ Fluor 488-conjugated Aβ_1-42. Results: Using our protocols, the average yield of isolated CD11b⁺ cells was around 2.2x10⁵ cells per brain. CD11b⁺CD45⁺CD39⁺ cells were defined here as microglia. The phagocytic activity of Aβ_1-42 by the isolated microglia was confirmed. LPSp (10 ng/ml) pre-treatment for 18 h significantly increased Aβ phagocytic activity. Conclusion: The enhancement of Aβ_1-42 phagocytosis by LPSp treatment in the primary mouse microglia was demonstrated for the first time.

from Cancer via ola Kala on Inoreader http://ift.tt/28YLEZt
via IFTTT

Immunopotentiator from Pantoea agglomerans 1 (IP-PA1) Promotes Murine Hair Growth and Human Dermal Papilla Cell Gene Expression

Background/Aim: The lipopolysaccharide (LPS)-like compound derived from Pantoea agglomerans (immunopotentiator from Pantoea agglomerans 1 (IP-PA1)) has been used not only as dietary supplement or cosmetic for humans, but also by Japanese veterinarians as an anti-tumor, anti-allergy, "keep a fine coat of fur" and hair growth-promoting functional food for dogs and cats. In the present study, we focused on the hair growth-promoting effects of IP-PA1 on a hair-shaved animal model and its mechanism of action. We also investigated its potential on gene expression after stimulating human dermal papilla cells with IP-PA1. Materials and Methods: The hair on the back of a C3H/HeN mouse was shaved and IP-PA1 was orally administered or applied to the skin. The status of hair growth was observed and recorded for 14 days. Skin was collected and histological tissue examination was performed with respect to hair growth status using hematoxylin and eosin staining. After IP-PA1 administration (2 and 10 μg/ml) to human dermal papilla cell culture system for 24 h, fibroblast growth factor-7 (FGF-7) and vascular endothelial growth factor (VEGF) mRNA expression were measured using real-time polymerase chain reaction (PCR) analysis. Results: IP-PA1, when given orally, showed a tendency to promote hair growth in mice. In addition, skin application also significantly promoted hair growth, while histopathological examinations further demonstrated hair elongation from dermal papilla cells. In the human dermal papilla cell culture system, significant FGF-7 and VEGF mRNA expressions were observed (p<0.05). Conclusion: An underlying mechanism of gene expression by which IP-PA1 promotes hair growth was suggested to be different from that of medicine and traditional hair tonics, such as minoxidil and adenosine.

from Cancer via ola Kala on Inoreader http://ift.tt/295EGFM
via IFTTT

Effect of Xenotransplantation Site on MicroRNA Expression of Human Colon Cancer Stem Cells

Background: Cancer stem cells (CSCs) have a high tumorigenic ability to form patient-derived tumor xenografts (PDXs). PDXs are an attractive pre-clinical model, but gene expression and biological behavior of cancer cells in the tumor will change during establishment and passage of PDXs. Materials and Methods: Human colon cancer PDX was established and passaged either subcutaneously or orthotopically into the murine intestine. Histology and flow cytometric profile of the surgical specimen and the PDX were analyzed. CSCs were then isolated from the tumors and their microRNA (miRNA) expression was analyzed by semi-quantitative polymerase chain reaction. Results: The surgical specimens and PDXs were histologically similar. The size of CSC population increased and expression of miRNAs in CSCs changed in the passaged PDXs. Expression of oncogenic miRNAs was highly up-regulated in the CSCs of the orthotopically passaged PDXs. Conclusion: The xenotransplantation site and the number of tumor passages affect the miRNA expression of human colon CSCs.

from Cancer via ola Kala on Inoreader http://ift.tt/28YLG3F
via IFTTT

Screening for Identification of Personalized Food to Promote Adiponectin Secretion in Patients with Cancer

Background/Aim: Adiponectin is secreted specifically from adipose tissue. Low serum adiponectin levels may cause metabolic syndrome, which is also a risk factor for carcinogenesis. Several studies have suggested a negative correlation between adiponectin and risk of cancers. This study examined the adiponectin secretion-promoting effect of food ingredients in adipose-derived stem cells (ADSCs) obtained from patients with cancer. Patients and Methods: ADSCs from 7 lifestyle disease cancer patients were differentiated into adipocytes. Subsequently, the adipocytes were treated with 49 food constituents. The adiponectin levels in cell culture supernatants were measured after 48 and 96 h. Results: Soy genistein extract, lychee low-molecular-weight polyphenol, olive extract and turmeric promoted adiponectin secretion. Conclusion: Food constituents that promoted adiponectin secretion were identified using ADSCs derived from patients. This study suggested the possibility of a new treatment approach to prevent cancer recurrence.

from Cancer via ola Kala on Inoreader http://ift.tt/295Exm1
via IFTTT

Liver Injury After Invariant NKT Cell Activation by Free Alpha-galactosylceramide and Alpha-galactosylceramide-loaded Dendritic Cells

Background/Aim: Both free alpha-galactosylceramide (αGalCer) and αGalCer-loaded dendritic cells (DCG) activate invariant natural killer T (iNKT) cells to varying degrees, with αGalCer inducing liver injury. We sought to evaluate liver injury by these two pathways. Materials and Methods: Mice were injected with αGalCer or DCG followed by analysis of serum alanine transaminase (ALT) activity levels, mortality and liver function. Results: While ALT levels were elevated after DCG in a tumor necrosis factor (TNF)-α-dependent manner, DCG did not cause lethal injury. More serious injury of liver CD31-positive endothelial cells (CD31⁺ EC) was observed in mice treated with αGalCer than with DCG. Furthermore, liver CD31⁺ EC of αGalCer-treated mice induced naïve liver lymphocytes to produce TNF-α. Conclusion: DCG treatment did not induce lethal liver injury. CD31⁺ EC may play an antigen-presenting role to iNKT cells after αGalCer treatment and may be a cause of lethal injury.

from Cancer via ola Kala on Inoreader http://ift.tt/28YLAJk
via IFTTT

Preoperative neutrophil-to-lymphocyte ratio plus platelet-to-lymphocyte ratio in predicting survival for patients with stage I–II gastric cancer

Abstract

Background

The preoperative neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR) are associated with poor prognosis of gastric cancer. We aimed to determine whether the combination of NLR and PLR (NLR–PLR) could better predict survival of patients after curative resection for stage I–II gastric cancer.

Methods

We collected data from the medical records of patients with stage I–II gastric cancer undergoing curative resection between December 2000 and November 2012 at the Sun Yat-sen Cancer Center. The preoperative NLR–PLR was calculated as follows: patients with both elevated NLR (≥2.1) and PLR (≥120) were given a score of 2, and patients with only one or neither were given a score of 1 or 0, respectively.

Results

Kaplan–Meier analysis and log-rank tests revealed significant differences in overall survival (OS) among patients with NLR–PLR scores of 0, 1 and 2 (P < 0.001). Multivariate analysis showed that OS was independently associated with the NLR–PLR score [hazard ratio (HR) = 1.51, 95% confidence interval (CI) 1.02–2.24, P = 0.039] and TNM stage (HR = 1.36, 95% CI 1.01–1.83, P = 0.041). However, other systemic inflammation-based prognostic scores, including the modified Glasgow prognostic score, the prognostic nutritional index, and the combination of platelet count and NLR, were not. In TNM stage-stratified analysis, the prognostic significance of NLR–PLR was maintained in patients with stage I (P < 0.001) and stage II cancers (P = 0.022). In addition, the area under the receiver operating characteristic curve for the NLR–PLR score was higher than those of other systemic inflammation-based prognostic scores (P = 0.001).

Conclusion

The preoperative NLR-PLR score is a useful predictor of postoperative survival in the patients with stage I–II gastric cancer and may help identify high-risk patients for rational therapy and timely follow-up.

from Cancer via ola Kala on Inoreader http://ift.tt/28Yi740
via IFTTT

Cirrhotic patients have good insight into their daily functional impairment despite prior hepatic encephalopathy: comparison with PROMIS norms

Abstract

Health-related quality of life (HRQOL) is an important determinant of prognosis in cirrhosis and hepatic encephalopathy (HE). However due to inherent cognitive dysfunction, insight into HRQOL severity in patients with liver disease may be impaired. To assess insight into HRQOL using PROMIS tools compared to norms in cirrhotic patients. PROMIS tools are validated HRQOL instruments that test the domains of anger, anxiety, depression, physical function, pain behavior/impact, sleep disturbances/impairment, and social activities/roles, compared to US-norms. Patients were administered the PROMIS tools, the results of which were reviewed using a visual comparison with thed norms. Then two Likert scales from 0 to 10 per domain were administered that inquired about (1) Surprise Intensity: 0–4: not surprised, 5–10: surprised; and (2) Expectancies: 0–4: results better than expected, 5:10: as/worse than expected. Comparisons between HE/no-HE were also performed. 203 cirrhotic patients (57 yrs., 62 % men, MELD 12, 83 HE) were included. All HE patients were controlled on therapy. Prior HE patients were significantly impaired on all PROMIS domains (p < 0.01) except anger, compared to the re st. The majority (76–85 %) were not surprised with their placement vis-à-vis the norms. Similarly, a majority (59–61 %) thought their results were worse or as expected. However, a third of patients found that their PROMIS results were better than expected. Prior HE status did not significantly impact expectations or surprise based on placement with the norms. The majority of cirrhotic patients, regardless of prior HE, have good insight regarding their HRQOL issues.

from Cancer via ola Kala on Inoreader http://ift.tt/295eOf9
via IFTTT

A molecular biology and phase II study of imetelstat (GRN163L) in children with recurrent or refractory central nervous system malignancies: a pediatric brain tumor consortium study

Abstract

Telomerase activation is critical in many cancers including central nervous system (CNS) tumors. Imetelstat is an oligonucleotide that binds to the template region of the RNA component of telomerase, inhibiting its enzymatic activity. We conducted an investigator-sponsored molecular biology (MB) and phase II study to estimate inhibition of tumor telomerase activity and sustained responses by imetelstat in children with recurrent CNS malignancies. In the MB study, patients with recurrent medulloblastoma, high-grade glioma (HGG) or ependymoma undergoing resection received one dose of imetelstat as a 2-h intravenous infusion at 285 mg/m², 12–24 h before surgery. Telomerase activity was evaluated in fresh tumor from surgery. Post-surgery and in the phase II study, patients received imetelstat IV (days 1 and 8 q21-days) at 285 mg/m². Imetelstat pharmacokinetic and pharmacodynamic studies were performed. Of two evaluable patients on the MB trial, intratumoral telomerase activity was inhibited by 95 % compared to baseline archival tissue in one patient and was inevaluable in one patient. Forty-two patients (40 evaluable for toxicity) were enrolled: 9 medulloblastomas, 18 HGG, 4 ependymomas, 9 diffuse intrinsic pontine gliomas. Most common grade 3/4 toxicities included thrombocytopenia (32.5 %), lymphopenia (17.5 %), neutropenia (12.5 %), ALT (7.5 %) and AST (5 %) elevation. Two patients died of intratumoral hemorrhage secondary to thrombocytopenia leading to premature study closure. No objective responses were observed. Telomerase inhibition was observed in peripheral blood mononuclear cells (PBMCs) for at least 8 days. Imetelstat demonstrated intratumoral and PBMC target inhibition; the regimen proved too toxic in children with recurrent CNS tumors.

from Cancer via ola Kala on Inoreader http://ift.tt/28YwuUo
via IFTTT

Prognostic value of the extent of resection in supratentorial WHO grade II astrocytomas stratified for IDH1 mutation status: a single-center volumetric analysis

Abstract

Current evidence supports a maximized extent of resection (EOR) in low-grade gliomas (LGG), regardless of different histological subtypes and molecular markers. We therefore evaluated the prognostic impact of extensive, mainly intraoperative (i)MRI-guided surgery in low-grade astrocytomas stratified for IDH1 mutation status. Retrospective assessment of 46 consecutive cases of newly diagnosed supratentorial WHO grade II astrocytomas treated during the last decade was performed. IDH1 mutation status was obtained for all patients. Volumetric analysis of tumor volumes was performed pre-, intra-, early postoperatively and at first follow-up. Survival analysis was conducted with uni-and multivariate regression models implementing clinical parameters and continuous volumetric variables. Median EOR was 90.4 % (range 17.5–100 %) and was increased to 94.9 % (range 34.8–100 %) in iMRI-guided resections (n = 33). A greater EOR was prognostic for increased progression-free survival (HR 0.23, p = 0.031) and time to re-intervention (TTR) (HR 0.23, p = 0.03). In IDH1 mutant patients, smaller residual tumor volumes were associated with increased TTR (HR 1.01, p = 0.03). IDH1 mutation (38/46 cases) was an independent positive prognosticator for overall survival (OS) in multivariate analysis (HR 0.09, p = 0.002), while extensive surgery had limited impact upon OS. In a subgroup of patients with ≥40 % EOR (n = 39), however, initial and residual tumor volumes were prognostic for OS (HR 1.03, p = 0.005 and HR 1.08, p = 0.007, respectively), persistent to adjustment for IDH1. No association between EOR and neurologic morbidity was found. In this analysis of low-grade astrocytomas stratified for IDH1, extensive tumor resections were prognostic for progression and TTR and, in patients with ≥40 % EOR, for OS.

from Cancer via ola Kala on Inoreader http://ift.tt/295leJf
via IFTTT

Children with minimal chance for cure: parent proxy of the child’s health-related quality of life and the effect on parental physical and mental health during treatment

Abstract

To assess health-related quality of life (HRQOL) from the time of diagnosis until disease progression in a cohort of children with diffuse intrinsic pontine glioma (DIPG). The assessment was collected from the perspectives of the child and their parents and evaluated the effect of the child's HRQOL on their parents' physical and mental well-being, thus providing insight into the optimal timing of palliative consultation, including anticipatory grief and bereavement services. This longitudinal study assessed 25 parents and their children, ages 2–17 years of age with DIPG across five time-points, baseline and weeks 2, 4, 6, 16, 24. Assessments included the PedsQL 4.0 Core Scales, PedsQL 3.0 Brain Tumor Scale, and Short-Form 36. HRQOL instruments were completed by the child (age ≥5 years) and parent-proxy (ages 2–17 years), with the parent completing the SF-36. Children's reports and parents' proxy of their child's HRQOL indicated poor physical functioning and increased anxiety at the initiation of therapy. A trending improvement in the children's HRQOL was reported by children and parents from baseline to week 6, with a decline at week 16. The childs' parent proxy reported cognitive problems, procedural anxiety and lower overall brain tumor HRQOL were assoicated with poorer self-reported parental mental status. Palliative care consultation should be initiated at the time of diagnosis and is supported in the high physical and emotional symptom burden reported by our patients, with heightened involvement initiated at 16 weeks. Prompt palliative care involvement, mitigating anxiety associated with clinic visits and procedures, management of brain tumor specific symptoms, advanced care planning, anticipatory grief and bereavement services, and care coordination may maximize HRQOL for patients and ensure positive long-term outcomes for parents of children with DIPG.

from Cancer via ola Kala on Inoreader http://ift.tt/28Ywljx
via IFTTT

SPIB is a novel prognostic factor in diffuse large B-cell lymphoma that mediates apoptosis via the PI3K-AKT pathway

Summary

Although the clinical outcomes of diffuse large B-cell lymphoma (DLBCL) have improved in the immunochemotherapy era, about one third of patients develop intractable disease. To improve clinical outcomes for these patients, it is important to identify those with poor prognosis prior to initial treatment in order to select optimal therapies. Here, we investigated the clinical and biological significance of SPIB, an Ets family transcription factor linked to lymphomagenesis, in DLBCL. We classified 134 DLBCL patients into SPIB negative (n = 108) or SPIB positive (n = 26) groups by immunohistochemical staining. SPIB positive patients had a significantly worse treatment response and poor prognosis compared with SPIB negative patients. Multivariate analysis for patient survival indicated that SPIB expression was an independent poor prognostic factor for both progression free survival (PFS) and overall survival (OS) (PFS, hazard ratio (HR) 2.65, 95% confidence interval (CI) 1.31-5.33, p = 0.006; OS, HR 3.56, 95% CI 1.43-8.91, p = 0.007). Subsequent analyses of the roles of SPIB expression in DLBCL pathogenesis revealed that SPIB expression in lymphoma cells resulted in resistance to the BH3-mimetic, ABT-263, and contributed to apoptosis resistance via the PI3K-AKT pathway. The inhibition of AKT phosphorylation re-sensitized SPIB expressing lymphoma cells to ABT-263 induced cell death. Together, our data indicate that SPIB expression is a clinically novel poor prognostic factor in DLBCL that contributes to treatment resistance, at least in part, through an anti-apoptotic mechanism.

This article is protected by copyright. All rights reserved.

from Cancer via ola Kala on Inoreader http://ift.tt/28Y2En8
via IFTTT

S100A4 accelerates the proliferation and invasion of endometrioid carcinoma and is associated with the ‘MELF’ pattern

Summary

Endometrioid carcinoma (EC) is one of the most common malignancies of the female genital system. Although the behavior of EC ranges from an excellent prognosis to aggressive disease with a poor outcome, the factors that determine its diversity have not been determined. Here, we show that S100A4, a calcium-binding protein of the EF-hand type, is correlated with the proliferation and invasion ability of EC. We demonstrated previously that EC cells with high aldehyde dehydrogenase (ALDH) activity were more tumorigenic than ALDH-lo cells. Screening by shotgun proteomics demonstrated that the expression level of S100A4 in ALDH-hi EC cells was significantly higher than that in ALDH-lo cells. S100A4-knockout cells generated by the CRISPR/Cas9 system showed reduced proliferation and invasion. These cells showed impaired AKT phosphorylation and matrix metalloproteinase-2 activation, accounting for their impaired proliferation and invasion, respectively. Furthermore, in clinical EC samples, elevated expression of S100A4 was highly related to myometrial and lymphatic invasion in well- to moderately-differentiated EC. Notably, strong and diffuse expression of S100A4 was observed in tumor tissues with a microcystic, elongated and fragmented ('MELF') pattern, which is associated with a highly invasive EC phenotype. Collectively, our results demonstrate not only that high expression of S100A4 contributes to an aggressive phenotype of EC, but also that its elevated expression is closely related to the MELF histopathological pattern.

This article is protected by copyright. All rights reserved.

from Cancer via ola Kala on Inoreader http://ift.tt/28YJlX8
via IFTTT

Maternal alcohol binge-drinking in the first trimester and the risk of orofacial clefts in offspring: a large population-based pooling study

Abstract

Using individual participant data from six population-based case–control studies, we conducted pooled analyses to examine maternal alcohol consumption and the risk of clefts among >4600 infants with cleft lip only, cleft lip with cleft palate, or cleft palate only and >10,000 unaffected controls. We examined two first-trimester alcohol measures: average number of drinks/sitting and maximum number of drinks/sitting, with five studies contributing to each analysis. Study-specific odds ratios (ORs) were estimated using logistic regression and pooled to generate adjusted summary ORs. Across studies, 0.9–3.2 % of control mothers reported drinking an average of 5+ drinks/sitting, while 1.4–23.5 % reported drinking a maximum of 5+ drinks/sitting. Compared with non-drinkers, mothers who drank an average of 5+ drinks/sitting were more likely to deliver an infant with cleft lip only (pooled OR 1.48; 95 % confidence intervals 1.01, 2.18). The estimate was higher among women who drank at this level 3+ times (pooled OR 1.95; 1.23, 3.11). Ever drinking a maximum of 5+ drinks/sitting and non-binge drinking were not associated with cleft risk. Repeated heavy maternal alcohol consumption was associated with an increased risk of cleft lip only in offspring. There was little evidence of increased risk for other cleft types or alcohol measures.

from Cancer via ola Kala on Inoreader http://ift.tt/298NCch
via IFTTT

Phase II evaluation of LY2603618, a first-generation CHK1 inhibitor, in combination with pemetrexed in patients with advanced or metastatic non-small cell lung cancer

Summary

Introduction LY2603618 is a selective inhibitor of checkpoint kinase 1 (CHK1) protein kinase, a key regulator of the DNA damage checkpoint, and is predicted to enhance the effects of antimetabolites, such as pemetrexed. This phase II trial assessed the overall response rate, safety, and pharmacokinetics (PK) of LY2603618 and pemetrexed in patients with non-small cell lung cancer (NSCLC). Methods In this open-label, single-arm trial, patients with advanced or metastatic NSCLC progressing after a prior first-line treatment regimen (not containing pemetrexed) and Eastern Cooperative Oncology Group performance status ≤2 received pemetrexed (500 mg/m², day 1) and LY2603618 (150 mg/m², day 2) every 21 days until disease progression. Safety was assessed using Common Terminology Criteria for Adverse Events v3.0. Serial blood samples were collected for PK analysis after LY2603618 and pemetrexed administration. Expression of p53, as measured by immunohistochemistry and genetic variant analysis, was assessed as a predictive biomarker of response. Results Fifty-five patients were enrolled in the study. No patients experienced a complete response; a partial response was observed in 5 patients (9.1 %; 90 % CI, 3.7–18.2) and stable disease in 20 patients (36.4 %). The median progression-free survival was 2.3 months (range, 0–27.1). Safety and PK of LY2603618 in combination with pemetrexed were favorable. No association between p53 status and response was observed. Conclusions There was no significant clinical activity of LY2603618 and pemetrexed combination therapy in patients with advanced NSCLC. The results were comparable with historical pemetrexed single-agent data, with similar safety and PK profiles being observed.

from Cancer via ola Kala on Inoreader http://ift.tt/28YBrgP
via IFTTT

Metabolic clusters of breast cancer in relation to gene- and protein expression subtypes

Abstract

Background

The heterogeneous biology of breast cancer leads to high diversity in prognosis and response to treatment, even for patients with similar clinical diagnosis, histology, and stage of disease. Identifying mechanisms contributing to this heterogeneity may reveal new cancer targets or clinically relevant subgroups for treatment stratification. In this study, we have merged metabolite, protein, and gene expression data from breast cancer patients to examine the heterogeneity at a molecular level.

Methods

The study included primary tumor samples from 228 non-treated breast cancer patients. High-resolution magic-angle spinning magnetic resonance spectroscopy (HR MAS MRS) was performed to extract the tumors metabolic profiles further used for hierarchical cluster analysis resulting in three significantly different metabolic clusters (Mc1, Mc2, and Mc3). The clusters were further combined with gene and protein expression data.

Results

Our result revealed distinct differences in the metabolic profile of the three metabolic clusters. Among the most interesting differences, Mc1 had the highest levels of glycerophosphocholine (GPC) and phosphocholine (PCho), Mc2 had the highest levels of glucose, and Mc3 had the highest levels of lactate and alanine. Integrated pathway analysis of metabolite and gene expression data uncovered differences in glycolysis/gluconeogenesis and glycerophospholipid metabolism between the clusters. All three clusters had significant differences in the distribution of protein subtypes classified by the expression of breast cancer-related proteins. Genes related to collagens and extracellular matrix were downregulated in Mc1 and consequently upregulated in Mc2 and Mc3, underpinning the differences in protein subtypes within the metabolic clusters. Genetic subtypes were evenly distributed among the three metabolic clusters and could therefore contribute to additional explanation of breast cancer heterogeneity.

Conclusions

Three naturally occurring metabolic clusters of breast cancer were detected among primary tumors from non-treated breast cancer patients. The clusters expressed differences in breast cancer-related protein as well as genes related to extracellular matrix and metabolic pathways known to be aberrant in cancer. Analyses of metabolic activity combined with gene and protein expression provide new information about the heterogeneity of breast tumors and, importantly, the metabolic differences infer that the clusters may be susceptible to different metabolically targeted drugs.

from Cancer via ola Kala on Inoreader http://ift.tt/28Y0MuC
via IFTTT

In silico designing, cloning, and heterologous expression of novel chimeric human B lymphocyte CD20 extra loop

Abstract

Design and production of monoclonal antibody for the diagnosis and immunotherapy of non-Hodgkin lymphoma require a suitable CD20 antigen as an effective immunogen. In this study, a new chimeric human CD20 extra loop (hCD20EXL) protein was designed by bioinformatics tools and was expressed in Escherichia coli BL21 DE3. Amino acid sequences, protein structure, immunogenicity, and other physicochemical property of potential antigens were in silico analyzed. Antigenicity, codon optimization, and other predictions of designed protein were determined by bioinformatics tools. The designed protein was heterologously expressed in E. coli and verified by SDS-PAGE and Western blot. Immunogenicity of this antigen was tested in mice, and reactivity of the antibodies was evaluated using flow cytometry. Experimental analysis confirmed the in silico prediction of the designed chimeric hCD20 in this study. Therefore, based on these results, it is suggested that the new chimeric hCD20 antigen could be an appropriate immunogen for production of monoclonal antibody in immunotherapy purposes.

from Cancer via ola Kala on Inoreader http://ift.tt/28YH1zr
via IFTTT

Silencing of ZRF1 impedes survival of estrogen receptor positive MCF-7 cells and potentiates the effect of curcumin

Abstract

The role and clinical implication of ZRF1 in breast cancer are poorly understood. So this study is aimed to explore the role of ZRF1 in breast cancer progression. With this context, we first assessed its expression pattern in FFPE primary and metastasis breast tissue samples as well as from publicly available databases. Moreover, we also explored the survival status of patients from the publicly available database and interestingly discover that high expression of ZRF1 decreases the survival of estrogen-positive breast cancer patients more than estrogen-negative status patients. In the perspective of this, we evaluated the role ZRF1 in MCF-7 breast cancer cells and found that it's silencing by knockdown results in decreased cell proliferation as well as cell viability. Results also show that expression of ZRF1 is down regulated in the presence of estrogen-depleted conditions but independent of RAS/MEK as well as AKT axes. Moreover, the decrease in viability of MCF-7 cells was accompanied by induction of apoptosis and DNA damage, well-marked with upregulation of cleaved PARP and downregulation of BCL2 and H2AUbK119 levels. Furthermore, we also explored that knockdown of ZRF1 sensitises the effect of curcumin, observed with decrease in cell viability and dropping of IC50 value from 25 to 15 μM. This investigation thus shed a new light on the role on ZRF1 in breast cancer cells and hence can be exploited to design better therapeutic intervention.

from Cancer via ola Kala on Inoreader http://ift.tt/28Y0MLa
via IFTTT

The C-reactive protein/albumin ratio predicts overall survival of patients with advanced pancreatic cancer

Abstract

Recent studies have demonstrated the prognostic value of the C-reactive protein/albumin (CRP/Alb) ratio in cancer. However, the role of the CRP/Alb ratio in advanced pancreatic cancer (PC) has not been examined. A retrospective study of 233 patients with advanced PC was conducted. We investigated the relationship between the CRP/Alb ratio, clinicopathological variables, and overall survival (OS). The optimal cutoff point of the CRP/Alb ratio was 0.54. A higher CRP/Alb ratio was significantly associated with an elevated neutrophil-lymphocyte ratio (NLR) (P < 0.001) and higher modified Glasgow prognostic score (mGPS) (P < 0.001). Using univariate analyses, we found that the age (P = 0.009), disease stage (P < 0.001), NLR (P < 0.001), mGPS (P < 0.001), and CRP/Alb ratio (P < 0.001) were significant predictors of OS. Patients with a higher CRP/Alb ratio had a worse OS than patients with a lower CRP/Alb ratio (hazard ratio (HR) 3.619; 95 % CI 2.681–4.886; P < 0.001). However, the CRP/Alb ratio was identified as the only inflammation-based parameter with an independent prognostic ability in the multivariate analyses (P < 0.001). The pretreatment CRP/Alb ratio is a superior prognostic and therapeutic predictor of OS in advanced PC.

from Cancer via ola Kala on Inoreader http://ift.tt/28YGYE7
via IFTTT

INPP4B-mediated DNA repair pathway confers resistance to chemotherapy in acute myeloid leukemia

Abstract

INPP4B has been recently shown to be a poor prognostic marker and confer chemo- or radio-resistance in AML cells, whereas, the underlying mechanisms remain unclear. Herein, we aimed to explore the possible mechanisms mediated the resistance to chemotherapy in AML. We found that INPP4B-mediated resistance to genotoxic drug, cytarabine, was accompanied by lower p-H2AX accumulation in KG-1 cells, and INPP4B knockdown evidently sensitized KG-1 cells to cytarabine, meanwhile, p-H2AX expression was increased dramatically. Then, we observed that INPP4B knockdown inhibited the loss of p-H2AX expression after cytarabine removal in INPP4B-silenced KG-1 cells, whereas, in control KG-1 cells, the expression of p-H2AX was reduced in a time-dependent manner. Next, INPP4B knockdown can significantly downregulate ATM expression and subsequently inhibit the activation of ATM downstream targets of p-ATM, p-BRCA1, p-ATR, and p-RAD51. Furthermore, nuclear localization of p65 was inhibited after INPP4B knockdown, and reactivation of p65 can rescue the INPP4B knockdown-induced inhibition of ATM, p-ATM, p-BRCA1, p-ATR, and p-RAD51. Finally, INPP4B expression was positively correlated with ATM expression in AML cells, both INPP4B knockdown and KU55933 can significantly sensitize primary myeloid leukemic cells to cytarabine treatment.

Collectively, these data suggest that enhanced ATM-dependent DNA repair is involved in resistance to chemotherapy in INPP4B^high AML, which could be mediated by p65 nuclear translocation, combination chemotherapy with INPP4B or DNA repair pathway inhibition represents a promising strategy in INPP4B^high AML.

from Cancer via ola Kala on Inoreader http://ift.tt/28Y0Mer
via IFTTT

Contemporary management of large-volume arteriovenous malformations: a clinician’s review

Abstract

Arteriovenous malformations (AVMs) represent a heterogeneous group of lesions, and as such, there exist several treatment options and approaches depending on size, location, grading, and symptoms. Large-volume AVMs represent a particularly challenging subset of AVMs with controversy over the very classification with definitions based on size, volume, and Spetzler-Martin grade. With regards to treatment paradigms, the natural history of these lesions is an important foundation upon which management principles have been built. At this time, management options range from observation with medical management to interventions including radiosurgery, microsurgery, embolization, or a combination of these approaches. In light of the challenges facing clinicians, we performed a literature review of AVMs with a specific focus on the management of large-volume AVMs with respect to outcomes, toxicity, and future treatment options. Based on the review, we have proposed a comprehensive risk-based treatment algorithm for the management of large-volume AVMs.

from Cancer via ola Kala on Inoreader http://ift.tt/29gKM47
via IFTTT

DNA Damage Is a Potential Marker for TP53 Mutation in Colorectal Carcinogenesis

Abstract

Purpose

The ability to measure oxidative DNA damage in a tissue allows establishment of the relationship between DNA damage and mutations in normal and neoplastic cells. It is well known that TP53 is a key inhibitor of tumor development and preserves the genome integrity in each cell. The aim of the present study was to investigate the relationship between DNA damage and TP53 mutation in colorectal adenoma and adenocarcinoma, and the value of DNA damage as potential marker of TP53 mutation in non-tumor tissues adjacent to colon malignant lesions.

Methods

Tissue samples were obtained by colonoscopy from patients with adenoma and/or adenocarcinoma and from healthy volunteers. Diagnosis was defined by histopathology. Immunohistochemistry with computer-assisted image analysis was performed to quantify TP53 mutation. Oxidative DNA damage was determined by comet assay. Statistical analyses were performed with 5 % of significance level.

Results

The TP53 level was higher in non-tumor tissues from tumor patients than in normal tissues from healthy volunteers (p = 0.01). Likewise, higher TP53 levels were observed in tumor tissues compared with the non-tumor tissues (p = 0.00). Oxidative DNA damage levels were higher in tumor tissues than in non-tumor tissues (p = 0.00). The amount of TP53 (p = 0.00) and oxidative DNA damage (p = 0.00) in normal and tumor tissue was related. The relationship between oxidative DNA damage and TP53 mutation was demonstrated in all samples (p = 0.00).

Conclusion

Oxidative DNA damage is an intervening variable for TP53 mutation in colorectal adenoma-carcinoma. Our data suggests that oxidative DNA damage is a potential marker of TP53 mutation in colorectal carcinogenesis.

from Cancer via ola Kala on Inoreader http://ift.tt/28YRMnI
via IFTTT

Fear of cancer recurrence: a theoretical review and novel cognitive processing formulation

Abstract

Purpose

Fear of cancer recurrence (FCR) is prevalent among survivors. However, a comprehensive and universally accepted theoretical framework of FCR to guide intervention is lacking. This paper reviews theoretical frameworks previously used to explain FCR and describes the formulation of a novel theoretical framework for FCR.

Methods

A systematic review of the literature was undertaken to identify conceptual frameworks or theories applied to FCR. MEDLINE, PubMED, CINAHL, AMED, PsycINFO and Web of Science were searched. Identified conceptual frameworks were reviewed for strength of evidence supporting their validity.

Results

Of 558 papers initially identified, 16 made reference to six different conceptual frameworks relating to FCR. The most comprehensive and evidence-based theoretical approach is the Common Sense Model (CSM). Other approaches have limited evidence supporting their application to FCR. Two theoretical approaches developed in the context of emotional disorders that appear to be highly relevant to FCR: the Self-Regulatory Executive Function (S-REF) model and Relational Frame Theory were combined with the CSM to produce a novel cognitive processing account of FCR.

Conclusions

Few conceptual frameworks have been used consistently to guide FCR research, and not all frameworks are empirically well supported, suggesting that further discussion regarding the conceptualisation of FCR is needed. The novel theoretical framework for FCR presented highlights the multidimensional nature of FCR and the importance of cognitive processing and metacognitions in the development and maintenance of FCR.

Implications for Cancer Survivors

The novel theoretical formulation of FCR outlined here provides a much-needed comprehensive framework to further investigate and address FCR in cancer survivors.

from Cancer via ola Kala on Inoreader http://ift.tt/28YRtsL
via IFTTT

Examining factors associated with self-management skills in teenage survivors of cancer

Abstract

Background

Monitoring long-term health of teenage cancer survivors is dependent on successful transition from pediatric to adult long-term follow-up (LTFU) care. This study identified factors associated with self-management skills (SMSs), an important correlate of successful transition.

Methods

Data were collected from a cross-sectional survey conducted at three Canadian hospitals between July 2011 and January 2012. The sample included 184 childhood cancer survivors aged between 15 and 19 years. Independent factors included demographic- and illness-related factors. The outcome of interest was SMSs, measured using the SMSs scale, with higher scores indicating more SMSs.

Results

More SMSs were associated positively with older age (β = 1.2, 95 % confidence interval (CI) = 0.1 to 2.4), being female (β = 4.6, 95 % CI = 1.9 to 7.4), and having a non-married parent (β = 5.2, 95 % CI = 0.04 to 10.4). There was a negative association between SMSs and having had a central nervous system tumor (CNS) compared to having leukemia (β = −7.9, 95 % CI = −13.5 to −2.2).

Conclusions

Younger, male, and CNS tumor survivors lack SMSs. Future research is needed to explore the extent and nature of associations between SMSs and parents' marital status.

Implications for cancer survivors

Younger, male, and CNS tumor survivors should be targeted for interventions in order to ensure that adequate SMSs are attained before completion of transition.

from Cancer via ola Kala on Inoreader http://ift.tt/29gKiea
via IFTTT

Lifestyle behaviors among US cancer survivors

Abstract

Purpose

We describe and compare lifestyle behaviors, including smoking, physical activity, alcohol consumption, and nutrition, among cancer survivors to individuals with no cancer.

Methods

Data from the 2013 Behavior Risk Factor Surveillance System were used for this cross-sectional study. Weighted analysis was performed, and associations were examined by adjusted prevalence ratios (APRs) and 95 % confidence intervals (CIs).

Results

Comparing survivors to individuals with no cancer history, differences were found for a smoking quit attempt (APR 1.08; CI 1.04, 1.12), physical inactivity (APR 1.11; CI 1.07, 1.15), and binge drinking (APR 0.89; CI 0.83, 0.95). An interaction with gender was observed when examining smoking and heavy drinking. Smoking was lower (APR 0.85; CI 0.79, 0.92) among male survivors than males with no cancer history, while higher (APR 1.25; CI 1.18, 1.32) among female survivors compared to females with no cancer history. Heavy drinking (APR 0.85; CI 0.73, 0.98) was lower among male survivors than males with no cancer history, while cancer survivorship was not associated with heavy drinking among females. No differences existed for fruit and vegetable consumption or body mass index.

Conclusions

US cancer survivors are not more likely than the general population to engage in all healthy lifestyle behaviors. Interventions, including improved physician communication, to reduce physical inactivity among all cancer survivors and cigarette smoking among female survivors are needed.

Implications for Cancer Survivors

Cancer survivors are at increased risk for comorbid conditions, and acceptance of healthy behaviors may reduce dysfunction and improve long-term health. Ultimately, opportunities exist for clinicians to promote lifestyle changes that may improve the length and quality of life of their patients.

from Cancer via ola Kala on Inoreader http://ift.tt/28YRXPy
via IFTTT

Prevalence and factors related to smoking and smoking cessation 6 months following a cancer diagnosis: a population-based study

Abstract

Purpose

Limited research has examined smoking amongst recent cancer survivors or the relative contribution of factors on smoking behaviour. This study aimed to describe amongst recent Australian cancer survivors (i) prevalence of smoking by cancer type, (ii) characteristics associated with continued smoking following diagnosis, (iii) intention to quit among those who continue to smoke and (iv) characteristics associated with quitting following diagnosis.

Method

Cross-sectional data were analysed from 1299 cancer survivors diagnosed with their first primary cancer recruited from two Australian cancer registries in Australia between 2006 and 2008.

Results

Of participants, 8.6 % reported current smoking. Participants who were younger and single or widowed reported higher odds of current smoking. Participants who had a certificate/diploma or tertiary education reported lower odds of smoking. Among current smokers, 53 % intended to quit in the future. Lung cancer survivors reported more than four times the odds of quitting smoking since diagnosis compared to other cancer types.

Conclusion

Of recent Australian cancer survivors, 14 % report continued smoking.

Implications for Cancer Survivors

Smoking following a cancer diagnosis is associated with increased risk of mortality and further morbidity. There is a need to target cessation efforts towards survivors who are younger, without a partner and with a low level of education.

from Cancer via ola Kala on Inoreader http://ift.tt/29gKdqG
via IFTTT

Adult childhood cancer survivors’ narratives of managing their health: the unexpected and the unresolved

Abstract

Purpose

Currently, 80 % of children diagnosed with cancer will be cured. However, many of these survivors go on to develop long-term health problems or late effects related to their previous cancer and therapy and require varying degrees of lifelong follow-up care. The purpose of this study was to identify the different ways that adult survivors of childhood cancer manage their medical and psychological challenges.

Methods

Data from in-depth interviews with 30 adult survivors of a childhood cancer (9 to 38 years after diagnosis, currently 22 to 43 years of age, 60 % women) were analyzed using qualitative, thematic narrative analysis methods.

Results

The survivors had not expected the medical, psychological, and social challenges that arose over time and that often remained unresolved. Five narrative themes revealed distinct ways that survivors managed their health challenges: (1) trying to forget cancer, (2) trusting the system to manage my follow-up care, (3) being proactive about my health, (4) stumbling from one problem to the next, and (5) struggling to find my way.

Conclusions

Variation exists in the ways in which childhood cancer survivors frame their health, their perceived significance of health challenges, strategies used to manage health, interactions with healthcare professionals and the health system, and parental involvement.

Implications for Cancer Survivors

This research provides novel insights that can be used to inform the development of patient-centered health services that promote the assessment and tailoring of care to the diverse ways survivors enact their agency, as well as their psychoeducational coping styles, therapeutic relationship needs, and information needs.

from Cancer via ola Kala on Inoreader http://ift.tt/28YRjl8
via IFTTT

Am I ready to return to work? Assisting cancer survivors to determine work readiness

Abstract

Purpose

A critical initial step in work re-entry involves the determination of work readiness. Cancer survivors have requested increased health care provider involvement in their work readiness decisions. However, there has been no exploration of current practices in determining work readiness, and thus no specific recommendations regarding how to assist survivors in answering the question: Am I ready to return to work?

Methods

To explore return to work following cancer and the workplace supports survivors require, we completed an exploratory qualitative study. We conducted semi-structured interviews with (i) cancer survivors (n = 16) and (ii) health care/vocational service providers (n = 16). Data were analyzed using thematic analysis. Themes specific to work readiness are discussed.

Results

Three key processes were deemed relevant to determining work readiness by health care providers and survivors: (1) assessing functional abilities in relation to job demands; (2) identifying survivor strengths and barriers to return to work; and (3) identifying supports available in the workplace. Challenges to work readiness determinations, were described by survivors and providers, related to: (i) the complexity of cancer, (ii) the accuracy of work readiness determinations, and (iii) the lack of established processes for addressing work goals.

Conclusions

Health care providers need to work collaboratively with survivors to determine if they are physically, cognitively, and emotionally ready to return to work, and with workplaces to determine if they are prepared to provide the necessary supports. Further stakeholder collaboration is also warranted.

Implications for Cancer Survivors

Supports from health care providers in determining work readiness can ensure survivors do not return to work either "too early" or "too late."

from Cancer via ola Kala on Inoreader http://ift.tt/29gK4Ud
via IFTTT

Exercise adherence in a randomized trial of exercise on aromatase inhibitor arthralgias in breast cancer survivors: the Hormones and Physical Exercise (HOPE) study

Abstract

Purpose

Up to 50 % of postmenopausal breast cancer survivors taking aromatase inhibitors (AIs) experience AI-associated arthralgias, or joint pain, which causes many to stop taking AIs and may inhibit exercise, despite known health benefits. We thus evaluated exercise adherence and factors associated with better exercise adherence in breast cancer survivors experiencing AI-induced arthralgia in the (HOPE) year long randomized controlled trial.

Methods

We included 61 HOPE women randomized to exercise (150 min/week of moderate-intensity aerobic exercise and twice-weekly supervised strength training). Our main outcomes were aerobic exercise measured with daily activity logs, attendance at supervised exercise sessions, and changes in cardiorespiratory fitness, measured maximal oxygen consumption (VO₂max). We examined means and standard deviations (SDs) for exercise adherence by demographic and medical characteristics and used the t test for mean differences. We also examined predictors of adherence using linear regression.

Results

On average, at the end of the year long trial, women reported 119 (SD 78) min/week of moderate-intensity aerobic exercise and participated in 70 % of supervised exercise training sessions. After adjustment for other factors that influence adherence, at 6 months postrandomization, only baseline VO₂max was associated with higher aerobic exercise levels and at 12 months, only older age predicted better supervised exercise training attendance.

Conclusions

Breast cancer survivors taking AIs and experiencing arthralgia are able to initiate and maintain a year long exercise program, regardless of other factors that influence activity levels.

Implications for Cancer Survivors

Breast cancer survivors can exercise at levels that have been shown to improve AI-associated arthralgia.

from Cancer via ola Kala on Inoreader http://ift.tt/28YRTPO
via IFTTT

Is a behavioral treatment for urinary incontinence beneficial to prostate cancer survivors as a follow-up care?

Abstract

Purpose

The American Cancer Society (ACS) recommends a follow-up care plan for urinary incontinence of prostate cancer survivors that includes pelvic floor muscle exercise (PFME). We examined potential impacts and access barriers of this recommendation with consideration of patients who normally do not seek such care.

Methods

We compared 267 participants of a clinical trial that tested a PFME-based treatment of urinary incontinence and 69 nonparticipants who declined the trial. All subjects were assessed at baseline, 3, and 6 months on leakage frequency, disease-specific quality of life (QOL), and physical well-being. The nonparticipants were interviewed to examine reasons for intervention refusal.

Results

The participating and nonparticipating groups did not differ in most baseline demographics and clinical variables except that the nonparticipants had lower baseline prostate-specific antigen (P ≤ 0.01), lower education levels, and higher likelihood of receiving surgery alone (both P ≤ 0.05). Nonparticipants exhibited significantly more frequent daily leakage, poorer urinary function and bother, and severer urinary problems at 3 and 6 months, as well as worse physical well-being at 6 months, relative to baseline, than the participants. The primary reason for refusal was economical, such as lacking transportation and time for participation.

Conclusions

Urinary function and QOL can worsen without appropriate follow-up care. It is important to make a PFME-based follow-up care program available to all incontinent prostate cancer survivors as recommended by ACS guidelines.

Implications for cancer survivors

Seeking PFME-based treatment is crucial for long-term urinary health outcomes even if present leakage is minor or financial challenge is a concern.

from Cancer via ola Kala on Inoreader http://ift.tt/29gKoST
via IFTTT

Efficient elimination of pancreatic cancer stem cells by hedgehog/GLI inhibitor GANT61 in combination with mTOR inhibition

Abstract

Background

Pancreatic cancer is one of the most lethal malignancies. The innovative treatments are required and now the cancer stem cells (CSCs) are expected to be an effective target for novel therapies. Therefore we investigated the significance of hedgehog (Hh) signaling in the maintenance of CSC-like properties of pancreatic cancer cells, in order to discover the key molecules controlling their unique properties.

Methods

Human pancreatic cancer cell lines, Capan-1, PANC-1, MIA PaCa-2 and Capan-1 M9 were used for our experiments in DMEM/F12 medium containing 10 % fetal bovine serum. Sphere formation assay, immunofluorescence staining, flow cytometric analysis and MTT cell viability assay were performed to investigate molecular signals and the efficacy in the treatment of pancreatic cancer cells.

Results

Inhibition of the Hh pathway significantly reduced the expression of stem cell marker CD133 and sphere formation, an index of self-renewal capacity, demonstrating the suppression of CSC-like properties. Moreover, the GLI inhibitor GANT61 induced greater reduction in sphere formation and cell viability of pancreatic cancer cells than the smoothened (SMO) inhibitor cyclopamine. This suggests that GLI transcription factors, but not SMO membrane protein, are the key molecules in the Hh pathway. The treatment using GANT61 in combination with the inhibition of mTOR, which is another key molecule in pancreatic CSCs, resulted in the efficient reduction of cell viability and sphere formation of an inhibitor-resistant cell line, showing the strong efficacy and wide range applicability to pancreatic CSC-like cells.

Conclusions

Thus, this novel combination treatment could be useful for the control of pancreatic cancer by targeting pancreatic CSCs. This is the first report of the efficient elimination of pancreatic cancer stem-like cells by the double blockage of Hh/GLI and mTOR signaling.

from Cancer via ola Kala on Inoreader http://ift.tt/298K6i7
via IFTTT

Clinical relevance of circulating cell-free microRNAs in ovarian cancer

Abstract

Ovarian cancer is the leading cause of death among gynecologic malignancies. Since ovarian cancer develops asymptomatically, it is often diagnosed at an advanced and incurable stage. Despite many years of research, there is still a lack of reliable diagnostic markers and methods for early detection and screening. Recently, it was discovered that cell-free microRNAs (miRNAs) circulate in the body fluids of healthy and diseased patients, suggesting that they may serve as a novel diagnostic marker. This review summarizes the current knowledge regarding the potential clinical relevance of circulating cell-free miRNA for ovarian cancer diagnosis, prognosis, and therapeutics. Despite the high levels of ribonucleases in many types of body fluids, most of the circulating miRNAs are packaged in microvesicles, exosomes, or apoptotic bodies, are binding to RNA-binding protein such as argonaute 2 or lipoprotein complexes, and are thus highly stable. Cell-free miRNA signatures are known to be parallel to those from the originating tumor cells, indicating that circulating miRNA profiles accurately reflect the tumor profiles. Since it is well established that the dysregulation of miRNAs is involved in the tumorigenesis of ovarian cancer, cell-free miRNAs circulating in body fluids such as serum, plasma, whole blood, and urine may reflect not only the existence of ovarian cancer but also tumor histology, stage, and prognoses of the patients. Several groups have successfully demonstrated that serum or plasma miRNAs are able to discriminate patients with ovarian cancer patients from healthy controls, suggesting that the addition of these miRNAs to current testing regimens may improve diagnosis accuracies for ovarian cancer. Furthermore, recent studies have revealed that changes in levels of cell-free circulating miRNAs are associated with the condition of cancer patients. Discrepancies between the results across studies due to the lack of an established endogenous miRNA control to normalize for circulating miRNA levels, as well as differing extraction and quantification methods, are the pitfalls to be resolved before clinical application. There is still a long way, however, before this can be achieved, and further evidence would make it possible to apply circulating cell-free miRNAs not only as biomarkers but also as potential therapeutic targets for ovarian cancer in the future.

from Cancer via ola Kala on Inoreader http://ift.tt/28ZvxR5
via IFTTT

Ras-association domain family 10 acts as a novel tumor suppressor through modulating MMP2 in hepatocarcinoma

Ras-association domain family 10 acts as a novel tumor suppressor through modulating MMP2 in hepatocarcinoma

Oncogenesis 5, e237 (June 2016). doi:10.1038/oncsis.2016.24

Authors: W Liu, J Wang, L Wang, C Qian, Y Qian, H Xuan, W Zhuo, X Li, J Yu & J Si

from Cancer via ola Kala on Inoreader http://ift.tt/28ZvCED
via IFTTT

Ric-8A gene deletion or phorbol ester suppresses tumorigenesis in a mouse model of GNAQQ209L-driven melanoma

Ric-8A gene deletion or phorbol ester suppresses tumorigenesis in a mouse model of GNAQQ209L-driven melanoma

Oncogenesis 5, e236 (June 2016). doi:10.1038/oncsis.2016.45

Authors: B R Patel & G G Tall

from Cancer via ola Kala on Inoreader http://ift.tt/28ZvAg6
via IFTTT

An essential role of Ffar2 (Gpr43) in dietary fibre-mediated promotion of healthy composition of gut microbiota and suppression of intestinal carcinogenesis

An essential role of Ffar2 (Gpr43) in dietary fibre-mediated promotion of healthy composition of gut microbiota and suppression of intestinal carcinogenesis

Oncogenesis 5, e238 (June 2016). doi:10.1038/oncsis.2016.38

Authors: S Sivaprakasam, A Gurav, A V Paschall, G L Coe, K Chaudhary, Y Cai, R Kolhe, P Martin, D Browning, L Huang, H Shi, H Sifuentes, M Vijay-Kumar, S A Thompson, D H Munn, A Mellor, T L McGaha, P Shiao, C W Cutler, K Liu, V Ganapathy, H Li & N Singh

from Cancer via ola Kala on Inoreader http://ift.tt/28ZvQeN
via IFTTT

Measuring total liver function on sulfur colloid SPECT/CT for improved risk stratification and outcome prediction of hepatocellular carcinoma patients

Abstract

Background

Assessment of liver function is critical in hepatocellular carcinoma (HCC) patient management. We evaluated parameters of [^99mTc] sulfur colloid (SC) SPECT/CT liver uptake for association with clinical measures of liver function and outcome in HCC patients.

Methods

Thirty patients with HCC and variable Child-Turcotte-Pugh scores (CTP A5-C10) underwent [^99mTc]SC SPECT/CT scans for radiotherapy planning. Gross tumor volume (GTV), anatomic liver volume (ALV), and spleen were contoured on CT. SC SPECT image parameters include threshold-based functional liver volumes (FLV) relative to ALV, mean liver-to-spleen uptake ratio (L/S_mean), and total liver function (TLF) ratio derived from the product of FLV and L/S_mean. Optimal SC uptake thresholds were determined by ROC analysis for maximizing CTP classification accuracy. Image metrics were tested for rank correlation to composite scores and clinical liver function parameters. Image parameters of liver function were tested for association to overall survival with Cox proportional hazard regression.

Results

Optimized thresholds on SC SPECT were 58 % of maximum uptake for FLV, 38 % for L/S_mean, and 58 % for TLF. TLF produced the highest CTP classification accuracy (AUC = 0.93) at threshold of 0.35 (sensitivity = 0.88, specificity = 0.86). Higher TLF was associated with lower CTP score: TLF_A = 0.6 (0.4–0.8) versus TLF_B = 0.2 (0.1–0.3), p < 10⁻⁴. TLF was rank correlated to albumin and bilirubin (|R| > 0.63). Only TLF >0.30 was independently associated with overall survival when adjusting for CTP class (HR = 0.12, 95 % CI = 0.02–0.58, p = 0.008).

Conclusions

SC SPECT/CT liver uptake correlated with differential liver function. TLF was associated with improved overall survival and may aid in personalized oncologic management of HCC patients.

from Cancer via ola Kala on Inoreader http://ift.tt/28ZvzZi
via IFTTT

Modulation of innate immunity in the tumor microenvironment

Abstract

A recent report from the Center for Disease Control identified melanoma as being among the highest causes of cancer-related mortalities in the USA. While interventions such as checkpoint blockade have made substantial impact in terms of improving response rates and overall survival, a significant number of patients fail to respond to treatment or become resistant to therapy. A better understanding of the tumor microenvironment in these patients becomes imperative for identifying immune suppressive mechanisms that impact the development of effective anti-tumor immune responses. We have investigated innate immune cells (dendritic cells, NK cells) in the tumor microenvironment (TME) in order to devise effective targeted anticancer immune therapies. We find that matrix metalloproteinase-2 (MMP-2), secreted from melanoma cells and stromal cells, cleaves IFNAR1 and stimulates TLR-2 on dendritic cells (DC) within the TME. Both these events independently culminate in programing the DCs to promote pro-tumorigenic T_H2 T cell differentiation. In addition, we have shown that NK cells become functionally exhausted in melanoma patients. We identified the expression of Tim-3 as one of the factors responsible for NK cell exhaustion and showed that anti-Tim3 antibodies partially reversed this exhaustion. We have initiated local intervention strategies such as intra-tumoral administration of DC activating Poly-ICLC and compared the efficacy of different TLR agonists and melanoma antigens for use as combination tumor vaccine in clinical trials. Such approaches will provide a unique insight into tumor biology and will facilitate in development of highly effective and cell type-specific immune therapies.

from Cancer via ola Kala on Inoreader http://ift.tt/28YJdcf
via IFTTT

Circulating immune cell phenotype can predict the outcome of lenalidomide plus low-dose dexamethasone treatment in patients with refractory/relapsed multiple myeloma

Abstract

Although the antimyeloma effect of lenalidomide is associated with activation of the immune system, the exact in vivo immunomodulatory mechanisms of lenalidomide combined with low-dose dexamethasone (Len-dex) in refractory/relapsed multiple myeloma (RRMM) patients remain unclear. In this study, we analyzed the association between immune cell populations and clinical outcomes in patients receiving Len-dex for the treatment of RRMM. Peripheral blood samples from 90 RRMM patients were taken on day 1 of cycles 1 (baseline), 2, 3, and 4 of Len-dex therapy. Peripheral blood CD3⁺, CD4⁺, and CD8⁺ cell frequencies were significantly decreased by 3 cycles of therapy, whereas NK cell frequency was significantly increased after the 3rd cycle. For the myeloid-derived suppressor cell (MDSC) subset, the frequency of granulocytic MDSCs transiently increased after the 1st cycle, whereas there was an increase in monocytic MDSC (M-MDSC) frequency after the 1st and 3rd cycles. Among 81 evaluable patients, failure to achieve a response of VGPR or greater was associated with a decrease in CD8⁺ cell frequency and increase in M-MDSC frequency after 3 cycles of Len-dex treatment. A high proportion of natural killer T (NKT)-like cells (CD3⁺/CD56⁺) prior to Len-dex treatment might predict a longer time to progression. In addition, patients with a smaller decrease in the frequency of both CD3⁺ cells and CD8⁺ cells by 3 cycles exhibited a longer time to the next treatment. These results demonstrated that early changes in immune cell subsets are useful immunologic indicators of the efficacy of Len-dex treatment in RRMM.

from Cancer via ola Kala on Inoreader http://ift.tt/29gvLz7
via IFTTT

Vulnerable elders survey and socioeconomic status predict functional decline and death among older women with newly diagnosed nonmetastatic breast cancer

BACKGROUND

The purpose of this study was to determine the ability of the Vulnerable Elders Survey (VES-13) to predict the composite outcome of functional decline and death within 12 months of breast cancer treatment among women 65 years old or older with newly diagnosed stage I to III breast cancer.

METHODS

Two hundred and six participants were recruited from ambulatory oncology clinics at an academic center between April 2008 and April 2013. Participants competed the VES-13 at baseline just before neoadjuvant/adjuvant treatment. The primary outcome, functional decline/death, was defined as either a decrease of at least 1 point on the Activities of Daily Living scale and/or the Instrumental Activities of Daily Living scale or death between baseline and 12 months (yes or no).

RESULTS

One hundred and eighty four participants (89%) completed 12 months of follow-up. Twenty-two percent functionally declined (n = 34) or died (n = 7). Univariately, with increasing VES-13 scores, the estimated risk of functional decline/death rose from 23% for participants with a VES-13 score of 3 to 76% for participants with a VES-13 score of 10. In multivariate logistic regression analysis, VES-13 scores (adjusted odds ratio, 1.37; 95% confidence interval, 1.18-1.57) and having a high school education or less (adjusted odds ratio, 2.47; 95% confidence interval, 1.08-5.65) were independent predictors of functional decline/death (area under the receiver operator curve, 0.79).

CONCLUSIONS

Among older women with newly diagnosed nonmetastatic breast cancer, approximately 1 in 5 functionally declined and/or died within 12 months of breast cancer treatment initiation. Women with high school education or less were disproportionately affected. The VES-13 is a useful instrument for the early identification of those at risk for functional decline and/or death. Cancer 2016. © 2016 American Cancer Society.

from Cancer via ola Kala on Inoreader http://ift.tt/29gpFPc
via IFTTT

Targeting microRNAs as key modulators of tumor immune response

Abstract

The role of immune response is emerging as a key factor in the complex multistep process of cancer. Tumor microenvironment contains different types of immune cells, which contribute to regulate the fine balance between anti and protumor signals. In this context, mechanisms of crosstalk between cancer and immune cells remain to be extensively elucidated. Interestingly, microRNAs (miRNAs) have been demonstrated to function as crucial regulators of immune response in both physiological and pathological conditions. Specifically, different miRNAs have been reported to have a role in controlling the development and the functions of tumor-associated immune cells. This review aims to describe the most important miRNAs acting as critical modulators of immune response in the context of different solid tumors. In particular, we discuss recent studies that have demonstrated the existence of miRNA-mediated mechanisms regulating the recruitment and the activation status of specific tumor-associated immune cells in the tumor microenvironment. Moreover, various miRNAs have been found to target key cancer-related immune pathways, which concur to mediate the secretion of immunosuppressive or immunostimulating factors by cancer or immune cells. Modalities of miRNA exchange and miRNA-based delivery strategies are also discussed. Based on these findings, the modulation of individual or multiple miRNAs has the potential to enhance or inhibit specific immune subpopulations supporting antitumor immune responses, thus contributing to negatively affect tumorigenesis. New miRNA-based strategies can be developed for more effective immunotherapeutic interventions in cancer.

from Cancer via ola Kala on Inoreader http://ift.tt/28YOikS
via IFTTT