Cancer by Sfakianakis Alexandros: 05/26/16

Πέμπτη 26 Μαΐου 2016

Chronic condition clusters and functional impairment in older cancer survivors: a population-based study

Abstract

Purpose

The purpose of the study is to identify chronic condition clusters at pre- and post-cancer diagnosis, evaluate predictors of developing clusters post-cancer, and examine the impact on functional impairment among older cancer survivors.

Methods

We identified 5991 survivors age 65 and older of prostate, breast, colorectal, lung, bladder, kidney, head and neck, and gynecologic cancer and non-Hodgkin lymphoma from the Surveillance, Epidemiology and End Results-Medicare Health Outcomes Survey resource. Survivors completed surveys pre- and post-cancer diagnosis on 13 chronic conditions and functional status. Among those with ≥2 conditions, exploratory factor analysis identified clusters of conditions. Differences in cluster frequency from pre- to post-cancer diagnosis were evaluated across the top five cancer types using chi-square tests. Modified Poisson regression models estimated the relative risk of developing clusters post-diagnosis. Chi-square tests evaluated associations between function and clusters.

Results

Clusters included the following: cardiovascular disease cluster (pre 6.1 % and post 7.7 %), musculoskeletal cluster (28.2 % and 29.3 %), metabolic cluster (14.9 % and 17.6 %), and the major depressive disorder risk (MDDr) + gastrointestinal (GI) + pulmonary condition cluster (5.8 % and 8.7 %). Increases in MDDr + GI + Pulmonary cluster from pre- to post-cancer diagnosis were observed for prostate, lung, and colorectal cancer survivors. Functional impairment was more prevalent in survivors with defined clusters, especially in MDDr + GI + pulmonary, compared to survivors with ≥2 un-clustered conditions.

Conclusions

Distinct condition clusters of two or more chronic conditions are prevalent among older cancer survivors. Cluster prevalence increases from pre- to post-cancer diagnosis and these clusters have a significant impact on functional limitations.

Implications for Cancer Survivors

Tailored management on specific multimorbidity patterns will have implications for functional outcomes among older survivors.

from Cancer via ola Kala on Inoreader http://ift.tt/20Iucx1
via IFTTT

Negative information-seeking experiences of long-term prostate cancer survivors

Abstract

Purpose

Many prostate cancer survivors have lasting symptoms and disease-related concerns for which they seek information. To understand survivors' information-seeking experiences, we examined the topics of their information searches, their overall perceptions of the search, and perceptions of their health information seeking self-efficacy (i.e., confidence in their ability to obtain information). We hypothesized that negative search experiences and lower health information seeking self-efficacy would be associated with certain survivor characteristics such as non-white race, low income, and less education.

Methods

This was a retrospective study using data from the Michigan Prostate Cancer Survivor Study (state-based survey of long-term prostate cancer survivor outcomes, N = 2499, response rate = 38 %). Participants recalled their last search for information and reported the topics and overall experience. We conducted multivariable regression to examine the association between survivor characteristics and the information-seeking experience.

Results

Nearly a third (31.7 %) of prostate cancer survivors (median age of 76 years and 9 years since diagnosis) reported having negative information-seeking experiences when looking for information. However, only 13.4 % reported having low health information-seeking self-efficacy. Lower income and less education were both significantly associated with negative information-seeking experiences.

Conclusions

Our findings suggest that many long-term prostate cancer survivors have negative experiences when searching for information, and lower income and less education were survivor factors related to negative information-seeking experiences.

Implications for cancer survivors

We advocate for ongoing, information needs assessment at the point-of-care as the survivorship experience progresses to assess and potentially improve survivors' quality of life.

from Cancer via ola Kala on Inoreader http://ift.tt/1sdZbpK
via IFTTT

The use of mass spectrometry for analysing metabolite biomarkers in epidemiology: methodological and statistical considerations for application to large numbers of biological samples

Abstract

Data quality is critical for epidemiology, and as scientific understanding expands, the range of data available for epidemiological studies and the types of tools used for measurement have also expanded. It is essential for the epidemiologist to have a grasp of the issues involved with different measurement tools. One tool that is increasingly being used for measuring biomarkers in epidemiological cohorts is mass spectrometry (MS), because of the high specificity and sensitivity of MS-based methods and the expanding range of biomarkers that can be measured. Further, the ability of MS to quantify many biomarkers simultaneously is advantageously compared to single biomarker methods. However, as with all methods used to measure biomarkers, there are a number of pitfalls to consider which may have an impact on results when used in epidemiology. In this review we discuss the use of MS for biomarker analyses, focusing on metabolites and their application and potential issues related to large-scale epidemiology studies, the use of MS "omics" approaches for biomarker discovery and how MS-based results can be used for increasing biological knowledge gained from epidemiological studies. Better understanding of the possibilities and possible problems related to MS-based measurements will help the epidemiologist in their discussions with analytical chemists and lead to the use of the most appropriate statistical tools for these data.

from Cancer via ola Kala on Inoreader http://ift.tt/1TCMrQr
via IFTTT

Diverse and Targetable Gene Rearrangements in Cancer

Triple-negative breast cancer (TNBC) and other molecularly heterogeneous malignancies present a significant clinical challenge due to a lack of high-frequency "driver" alterations amenable to therapeutic intervention. These cancers often exhibit genomic instability, resulting in chromosomal rearrangements that impact the structure and expression of protein-coding genes. However, identification of these rearrangements remains technically challenging. Using a newly developed approach that quantitatively predicts gene rearrangements in tumor-derived genetic material, we identified and characterized a novel oncogenic fusion involving the MER proto-oncogene tyrosine kinase (MERTK) and discovered a clinical occurrence and cell line model of the targetable FGFR3-TACC3 fusion in TNBC. Expanding our analysis to other malignancies, we identified a diverse array of novel and known hybrid transcripts, including rearrangements between non-coding regions and clinically relevant genes such as ALK, CSF1R, and CD274/PD-L1. The over 1000 genetic alterations we identified highlight the importance of considering non-coding gene rearrangement partners, and the targetable gene fusions identified in TNBC demonstrate the need to advance gene fusion detection for molecularly heterogeneous cancers.

from Cancer via ola Kala on Inoreader http://ift.tt/20J2Nv4
via IFTTT

Metastasis suppression by E6AP

Metastatic disease is the major cause of breast cancer related death and despite many advances, current therapies are rarely curative. Tumor cell migration and invasion require actin cytoskeletal reorganisation to endow cells with capacity to disseminate and initiate the formation of secondary tumors. However, it is still unclear how these migratory cells colonise distant tissues to form macrometastases. The E6-associated protein, E6AP, acts both as an E3 ubiquitin-protein ligase and as a coactivator of steroid hormone receptors. We report that E6AP suppresses breast cancer invasiveness, colonisation and metastasis in mice, and in breast cancer patients, loss of E6AP associates with poor prognosis, particularly for basal breast cancer. E6AP regulates actin cytoskeletal remodelling via regulation of Rho-GTPases, acting as a negative regulator of ECT2, a GEF required for activation of Rho-GTPases. E6AP promotes ubiquitination and proteasomal degradation of ECT2 for which high expression predicts poor prognosis in breast cancer patients. We conclude that E6AP suppresses breast cancer metastasis by regulating actin cytoskeleton remodelling through the control of ECT2 and Rho-GTPase activity. These findings establish E6AP as a novel suppressor of metastasis and provide a compelling rationale for inhibition of ECT2 as a therapeutic approach for patients with metastatic breast cancer.

from Cancer via ola Kala on Inoreader http://ift.tt/1sSsXRI
via IFTTT

telomerase activity in pancreatic cyst fluid

Purpose: Pancreatic cysts frequently pose clinical dilemmas. On one hand, cysts with high-grade dysplasia offer opportunities for cure, on the other hand, those with low-grade dysplasia are easily over treated. Cyst fluid markers have the potential to improve the evaluation of these cysts. Since telomerase activity is commonly activated in malignant cells, we evaluated the diagnostic performance of cyst fluid telomerase activity measurements for predicting histologic grade. Experimental design: Telomerase activity was measured using telomerase repeat amplification with digital-droplet PCR in surgically-aspirated cyst fluid samples from 219 patients who underwent pancreatic resection for a cystic lesion (184, discovery, 35 validation) and 36 patients who underwent endoscopic ultrasound fine needle aspiration. Methodological and clinical factors associated with telomerase activity were examined. Results: Telomerase activity was reduced in samples that had undergone prior thawing. Among 119 samples not previously thawed, surgical cyst fluids from cystic neoplasms with high-grade dysplasia +/- associated invasive cancer had higher telomerase activity (median [interquartile range], 1158 [295.9-13033] copies/μL of cyst fluid than those without (19.74 [2.58-233.6] copies/μL) (P < 0.001). Elevated cyst fluid telomerase activity had a diagnostic accuracy for invasive cancer/high-grade dysplasia of 88.1% (discovery), 88.6% (validation), and 88.2% (merged). Among cysts classified preoperatively as having "worrisome features", cyst fluid telomerase activity had high diagnostic performance (sensitivity 73.7%, specificity 90.6%, accuracy, 86.1%). In multivariate analysis, telomerase activity independently predicted the presence of invasive cancer/high-grade dysplasia. Conclusion: Cyst fluid telomerase activity can be a useful predictor of the neoplastic grade of pancreatic cysts.

from Cancer via ola Kala on Inoreader http://ift.tt/20J3sfM
via IFTTT

Breast Cancer Integrative Oncology Care and Its Costs

Background. Naturopathic oncology in conjunction with conventional treatment is commonly referred to as integrative oncology (IO). Clinics directed by oncology board certified NDs (Fellows of the American Board of Naturopathic Oncology or FABNOs) provide high-quality data for describing IO therapies, their costs and measuring clinical outcomes. Purpose. To describe the types of IO therapies prescribed to breast cancer patients by ND FABNO physicians. Study participants (n = 324). Women who sought care at 1 of 6 naturopathic oncology clinics in Washington State were asked to enroll in a prospective 5 year observational outcomes study. Methods. Medical records were abstracted to collect treatment recommendations and cost data. Results. More than 72 oral or topical, nutritional, botanical, fungal and bacterial-based medicines were prescribed to the cohort during their first year of IO care. Trametes versicolor was prescribed to 63% of the women. Mind-body therapy was recommended to 45% of patients, and 49% received acupuncture. Also, 26% were prescribed injectable therapy, including mistletoe, vitamin B complex (12%), IV ascorbate (12%), IV artesunate (7%), and IV nutrition and hydration (4%). Costs ranged from $1594/year for early-stage breast cancer to $6200/year for stage 4 breast cancer patients. Of the total amount billed for IO care for 1 year for breast cancer patients, 21% was out-of-pocket. Conclusions. IO care for women with breast cancer consists of botanical and mushroom oral therapies, parenteral botanical and nutrient therapy, mind-body medicine and acupuncture. IO clinic visits and acupuncture are partially paid for by medical insurance companies.

from Cancer via ola Kala on Inoreader http://ift.tt/24azdiL
via IFTTT

The Antimetastatic and Antiangiogenesis Effects of Kefir Water on Murine Breast Cancer Cells

Background. Kefir is a unique cultured product that contains beneficial probiotics. Kefir culture from other parts of the world exhibits numerous beneficial qualities such as anti-inflammatory, immunomodulation, and anticancer effects. Nevertheless, kefir cultures from different parts of the world exert different effects because of variation in culture conditions and media. Breast cancer is the leading cancer in women, and metastasis is the major cause of death associated with breast cancer. The antimetastatic and antiangiogenic effects of kefir water made from kefir grains cultured in Malaysia were studied in 4T1 breast cancer cells. Methods. 4T1 cancer cells were treated with kefir water in vitro to assess its antimigration and anti-invasion effects. BALB/c mice were injected with 4T1 cancer cells and treated orally with kefir water for 28 days. Results. Kefir water was cytotoxic toward 4T1 cells at IC₅₀ (half-maximal inhibitory concentration) of 12.5 and 8.33 mg/mL for 48 and 72 hours, respectively. A significant reduction in tumor size and weight (0.9132 ± 0.219 g) and a substantial increase in helper T cells (5-fold) and cytotoxic T cells (7-fold) were observed in the kefir water–treated group. Proinflammatory and proangiogenic markers were significantly reduced in the kefir water–treated group. Conclusions. Kefir water inhibited tumor proliferation in vitro and in vivo mainly through cancer cell apoptosis, immunomodulation by stimulating T helper cells and cytotoxic T cells, and anti-inflammatory, antimetastatic, and antiangiogenesis effects. This study brought out the potential of the probiotic beverage kefir water in cancer treatment.

from Cancer via ola Kala on Inoreader http://ift.tt/1TMqlhO
via IFTTT

A pilot trial of FLOT neoadjuvant chemotherapy for resectable esophagogastric junction adenocarcinoma

Abstract

Docetaxel is active in esophagogastric junction (EGJ) adenocarcinoma, and DCF (docetaxel/cisplatin/5-fluorouracil) has shown good results in the neoadjuvant setting. Its high rate of grade 3–4 mucosal toxicity (stomatitis and diarrhea) has limited its widespread adoption. A more recent docetaxel-based triplet, FLOT (5-fluorouracil, oxaliplatin and docetaxel) may be better tolerated. We conducted a pilot study of FLOT chemotherapy in EGJ adenocarcinoma patients and dysphagia to prospectively assess the rate of grade 3–4 mucosal toxicity and of pathological complete response (pCR) rate. Dysphagia and quality of life were measured with validated questionnaires. Ten patients were enrolled. Grade 3–4 mucosal toxicity rate was 0 %; pCR rate was 11 %; and near-complete pathological response rate 11 %. Dysphagia improvement or resolution was seen in 90 % of patients, and quality of life was stable before and after chemotherapy. FLOT is a safe and active neoadjuvant chemotherapy option for EGJ adenocarcinoma and should be compared to other standard regimens in randomized trials.

from Cancer via ola Kala on Inoreader http://ift.tt/24ayrCl
via IFTTT

A look inside the mechanistic black box: Are red blood cells the critical effectors of RRx-001 cytotoxicity?

Abstract

The therapeutic potential of epi-immunotherapeutic anticancer agent RRx-001 in cancer has been validated with preclinical and clinical studies, since RRx-001 has successfully completed a phase 1 trial and multiple single-agent and combination phase 2 trials with preliminary evidence of promising activity are underway. Previous experimental work has implicated diverse anticancer mechanisms such as oxidative stress, ATP and NADPH depletion, anti-angiogenesis and epigenetic modulation in the overall antitumor effect of RRx-001. The hypothesis of this study was that the RRx-001 red blood cells are the essential and de facto intermediaries responsible for the reprograming of tumor behavior via transfer of their intracellular and membrane contents. To test this hypothesis, and thereby resolve the "black box" incompleteness in the continuity of the mechanism, the fate of red blood cells incubated with RRx-001 was explored in vitro and in vivo both in healthy animals and in tumor-bearing mice. The collective results establish that RRx-001-derivatized red blood cells are the critical "missing links" to explain the specificity and anticancer activity of RRx-001, including its immunomodulatory effects on tumor-associated macrophages. These experimental results delineate a novel erythrocyte-based mechanism without precedent in the annals of oncology and open the door to rational combination strategies with RRx-001 both in cancer therapy and beyond, particularly in disease states that affect red blood cell and vascular function such as malaria, leishmaniasis, sickle-cell disease and hemorrhagic shock.

from Cancer via ola Kala on Inoreader http://ift.tt/1TMq4vl
via IFTTT

Hawaii natural compounds are promising to reduce ovarian cancer deaths

10.1080/15384047.2016.1178428<br/>David J. Fei-Zhang

from Cancer via ola Kala on Inoreader http://ift.tt/1Z4RzR3
via IFTTT

Patterns and trends in the incidence of paediatric and adult germ cell tumours in Australia, 1982–2011

Publication date: August 2016
Source:Cancer Epidemiology, Volume 43
Author(s): Marina T. van Leeuwen, Howard Gurney, Jennifer J. Turner, Sandra L. Turner, Sallie-Anne Pearson, Maarit A. Laaksonen, Paul Harnett, Bavanthi Balakrishnar, Dhanusha Sabanathan, Claire M. Vajdic
PurposeGerm cell tumour (GCT) aetiology is uncertain and comprehensive epidemiological studies of GCT incidence are few.MethodsNationwide data on all malignant GCTs notified to Australian population-based cancer registries during 1982–2011 were obtained. Age- and sex-specific, and World age-standardised incidence rates were calculated for paediatric (0–14) and adult (15+) cases using the latest WHO subtype classification scheme. Temporal trends were examined using Joinpoint regression.ResultsThere were 17,279 GCTs (552 paediatric, 16,727 adult). Age-specific incidence in males (all histologies combined) was bimodal, with peaks during infancy for most sites, and second, larger, peaks during young adulthood. Incidence of ovarian tumours peaked at age 15–19. Around half of paediatric tumours were extragonadal, whereas adult tumours were mostly gonadal. Yolk sac tumours and teratomas predominated in infants, whereas germinomas became more frequent towards adulthood. Increasing incidence trends for some adult gonadal tumours have stabilised; the trend for male extragonadal tumours is also declining.ConclusionBroad similarities in the shape of age-specific incidence curves, particularly for gonadal, central nervous system, and mediastinal tumours provide epidemiological support for commonalities in aetiology among clinically disparate GCT subtypes. Differences in peak ages reflect underlying subtype-specific biological differences. Declining incidence trends for some adult gonadal tumours accords with the global transition in GCT incidence, and supports the possibility of a reduction in prevalence of shared aetiological exposures.

from Cancer via ola Kala on Inoreader http://ift.tt/1Z3Ah6M
via IFTTT

The use of mass spectrometry for analysing metabolite biomarkers in epidemiology: methodological and statistical considerations for application to large numbers of biological samples

Abstract

from Cancer via ola Kala on Inoreader http://ift.tt/1TCMrQr
via IFTTT

Elevated MTSS1 expression associated with metastasis and poor prognosis of residual hepatitis B-related hepatocellular carcinoma

Hepatectomy generally offers the best chance of long-term survival for patients with hepatocellular carcinoma (HCC). Many studies have shown that hepatectomy accelerates tumor metastasis, but the mechanism rem...

from Cancer via ola Kala on Inoreader http://ift.tt/1WXeU9W
via IFTTT

Improved 6-year overall survival in AT/RT – results of the registry study Rhabdoid 2007

Abstract

Atypical teratoid rhabdoid tumors (AT/RT) are characterized by mutations and subsequent inactivation of SMARCB1 (INI1, hSNF5), a predilection for very young children and an unfavorable outcome. The European Registry for rhabdoid tumors (EU-RHAB) was established to generate a common European database and to establish a standardized treatment regimen as the basis for phase I/II trials. Thus, genetic analyses, neuropathologic and radiologic diagnoses, and a consensus treatment regimen were prospectively evaluated. From 2005 to 2009, 31 patients with AT/RT from four countries were recruited into the registry study Rhabdoid 2007 and treated with systemic and intraventricular chemotherapy. Eight patients received high-dose chemotherapy, 23 radiotherapy, and 17 maintenance therapy. Reference evaluations were performed in 64% (genetic analyses, FISH, MLPA, sequencing) up to 97% (neuropathology, INI1 stain). Germ-line mutations (GLM) were detected in 6/21 patients. Prolonged overall survival was associated with age above 3 years, radiotherapy and achievement of a complete remission. 6-year overall and event-free survival rates were 46% (±0.10) and 45% (±0.09), respectively. Serious adverse events and one treatment-related death due to insufficiency of a ventriculo peritoneal shunt (VP-shunt) and consecutive herniation were noted. Acquisition of standardized data including reference diagnosis and a standard treatment schedule improved data quality along with a survival benefit. Treatment was feasible with significant but manageable toxicity. Although our analysis is biased due to heterogeneous adherence to therapy, EU-RHAB provides the best available basis for phase I/II clinical trials.

Atypical teratoid rhabdoid tumors (AT/RT) remain enigmatic tumors with no current standard of therapy. Long-term survival data on consistently treated patients are missing. Our study provides improved long-term survival data and lays the foundation for future phase I/II clinical trials. It demonstrates the feasibility of generating high-quality evidence by employing a registry trial.

from Cancer via ola Kala on Inoreader http://ift.tt/25ob6TD
via IFTTT

Stratifying prostate cancer patients by relative lymph node involvement: population- and modeling-based study

Abstract

It is estimated that about 10% of new prostate cancer (PCa) cases are lymph node-positive (LN+). We have previously discussed the role of the inflection point (IP) of an inverse Gompertzian survival curve as a surrogate for disease incurability. In this study, we aimed to stratify curability of different patient cohorts with pathologically positive lymph nodes through modeling survival curves by different percentages of LN involvement (%LN+) postoperatively and calculating associated IPs. From the Surveillance, Epidemiology, and End Results (SEER) database, we selected LN+ PCa patients undergoing radical prostatectomy. Modeling of relative survival curves using inverse Gompertzian kinetics for increasing value of maximal %LN+ involvement allowed stratification of cohort into groups with <10%, 10–40%, and greater or equal to 40% of LN+ out of all LNs sampled. Data were retrieved for 5903 patients. For the entire cohort, relative survival was 96%, 87%, and 76% at 5, 10, and 15 years, respectively. For %LN +, <10% the IP was about 27 years postoperatively. Patients with 10–40% LN+ had an IP at about 10 years; for those with more than 40% LN+, the IP was 7 years. A 10-year relative survival decreases from 97% for <10% LN+ to 71% for more than 40% LN+. While better therapies for LN + PCa are badly needed, this patient cadre is not homogenous and should be stratified by %LN+ in future clinical trials.

We stratify curability of lymph node-positive (LN+) patient cadres by modeling survival curves for different relative LN involvement (%LN+) and calculating respective inflection points associated with treatment failure. We show that the LN+ patient population is not homogenous and should be stratified by %LN+ in future clinical trials.

from Cancer via ola Kala on Inoreader http://ift.tt/1Z3mrBh
via IFTTT

The effect of amifostine on differentiation of the human megakaryoblastic Dami cell line

Abstract

Amifostine is a cytoprotective drug that was initially used to control and treat nuclear radiation injury and is currently used to provide organ protection in cancer patients receiving chemotherapy. Clinical studies have also found that amifostine has some efficacy in the treatment of cytopenia caused by conditions such as myelodysplastic syndrome and immune thrombocytopenia, both of which involve megakaryocyte maturation defects. We hypothesized that amifostine induced the differentiation of megakaryocytes and investigated this by exposing the human Dami megakaryocyte leukemia cell line to amifostine (1 mmol/L). After 12 days of amifostine exposure, optical microscopy showed that the proportion of Dami cells with diameters >20 μm had increased to 24.63%. Transmission electron microscopy identified the development of a platelet demarcation membrane system, while flow cytometry detected increased CD41a expression and decreased CD33 expression on the Dami cell surface. Ploidy analysis found that the number of polyploid cells with >4N DNA content increased to 27.96%. We did not detect any elevation in the mRNA or protein levels of megakaryocytic differentiation-associated transcription factors GATA-binding factor 1 (GATA-1) and nuclear factor, erythroid 2 (NF-E2), but nuclear import assay revealed an increased nuclear translocation of these proteins. These findings indicate that amifostine induced the differentiation of Dami cells into mature megakaryocytes via a mechanism involving increased nuclear translocation of the transcription factors, NF-E2 and GATA-1.

Dami cells increased in size and DNA ploidy during amifostine exposure; amifostine induced megakaryoblast differentiation via a mechanism involving increased nuclear translocation of GATA-1 and NF-E2.

from Cancer via ola Kala on Inoreader http://ift.tt/1qM12AR
via IFTTT

Racial disparities in renal cell carcinoma: a single-payer healthcare experience

Abstract

Significant racial disparities in survival for renal cell carcinoma (RCC) exist between white and black patients. Differences in access to care and comorbidities are possible contributors. To investigate if racial disparities persist when controlling for access to care, we analyzed data from a single-payer healthcare system. As part of a case–control study within the Kaiser Permanente Northern California system, pathologic and clinical records were obtained for RCC cases (2152 white, 293 black) diagnosed from 1998 to 2008. Patient demographics, comorbidities, tumor characteristics, and treatment status were compared. Overall survival and disease-specific survival (DSS) were calculated by the Kaplan–Meier method. A Cox proportion hazards model estimated the independent associations of race, comorbidity, and clinicopathologic variables with DSS. We found that compared to white patients, black patients were diagnosed at a younger age (median 62 vs. 66 years, P < 0.001), were more likely to have papillary RCC (15% vs. 5.2%, P < 0.001), and had similar rates of surgical treatment (78.8% vs. 77.9%, P = 0.764). On multivariate analysis, advanced American Joint Committee on Cancer (AJCC) stage, lack of surgical treatment, larger tumor size, and higher grade were predictors of worse DSS. Race was not an independent predictor of survival. Therefore, we conclude that within a single healthcare system, differences in characteristics of black and white patients with RCC persist; black patients had different comorbidities, were younger, and had decreased tumor stage. However, unlike other series, race was not an independent predictor of DSS, suggesting that survival differences in large registries may result from barriers to healthcare access and/or comorbidity rather than disease biology.

Various articles have identified health disparities in black patients with kidney cancer. We investigate racial disparities in a single-healthcare payer system. Race is no longer a predictor of survival suggesting barriers to healthcare access may be responsible for the worse outcomes observed in other large datasets.

from Cancer via ola Kala on Inoreader http://ift.tt/1P0L2X4
via IFTTT

Former smokers with non-small-cell lung cancers: a comprehensive investigation of clinicopathologic characteristics, oncogenic drivers, and prognosis

Abstract

The aim of this present investigation was to evaluate the clinicopathologic characteristics, oncogenic drivers, and prognosis of former smokers with non-small-cell lung cancer (NSCLC), and to compare them with those of the current and never smokers. This investigation was a single-institution retrospective study of 2289 NSCLC patients, who were classified as former, current, or never smokers. A collection was made of the clinicopathological characteristics, spectra of well-identified driver genes and survival rates. The survival rates were compared using log-rank test, and independent prognostic factors, identified using Cox regression analysis. Of 2289 NSCLC patients, 257 (11.2%) were former smokers; 868 (37.9%), current smokers; and 1164 (50.9%), never smokers. Compared with the current, the former were characterized by older age at diagnosis (64.3y vs. 59.9y; P < 0.001), earlier TNM stage (stage I, 47.9% vs. 39.5%; P = 0.017), fewer solid predominance in adenocarcinomas (16.2% vs. 29.5%; P = 0.005), and more EGFR mutation (33.2% vs. 20.7%; P < 0.001) but less KRAS mutation (6.7% vs. 11.9%, P = 0.041). No statistically significant survival differences were observed between the former and current. However, the light former smokers presented favorable overall survival when compared with the light current and heavy former or current (the light former vs. the heavy former, P = 0.028; the light former vs. the light current, P = 0.048; and the light former vs. the heavy current, P = 0.048). Our findings suggest that the former smokers with NSCLCs can have distinctive clinicopathologic characteristics, oncogenic drivers, and prognosis, and they, especially the light former, can benefit from smoking cessation.

Smoking cessation has much benefit, especially for those smokers who are diagnosed of lung cancer. In this study, we performed a research on former smokers with NSCLCs and demonstrated that former smokers with NSCLCs had distinctive characteristics and benefited from their cessation behavior.

from Cancer via ola Kala on Inoreader http://ift.tt/1P0LaWs
via IFTTT

Role of DUSP1/MKP1 in tumorigenesis, tumor progression and therapy

Abstract

Dual-specificity phosphatase-1 (DUSP1/MKP1), as a member of the threonine-tyrosine dual-specificity phosphatase family, was first found in cultured murine cells. The molecular mechanisms of DUSP1-mediated extracellular signal-regulated protein kinases (ERKs) dephosphorylation have been subsequently identified by studies using gene knockout mice and gene silencing technology. As a protein phosphatase, DUSP1 also downregulates p38 MAPKs and JNKs signaling through directly dephosphorylating threonine and tyrosine. It has been detected that DUSP1 is involved in various functions, including proliferation, differentiation, and apoptosis in normal cells. In various human cancers, abnormal expression of DUSP1 was observed which was associated with prognosis of tumor patients. Further studies have revealed its role in tumorigenesis and tumor progression. Besides, DUSP1 has been found to play a role in tumor chemotherapy, immunotherapy, and biotherapy. In this review, we will focus on the function and mechanism of DUSP1 in tumor cells and tumor treatment.

This review focuses on the function and mechanism of DUSP1 in tumor carcinogenesis and progression. DUSP1 promotes resistance to chemotherapy and radiation in various cancers and plays a role in tumor immunotherapy and biotherapy. Targeting DUSP1 could overcome the impaired efficacy caused by drug resistance and significantly improve current antitumor drugs' activity.

from Cancer via ola Kala on Inoreader http://ift.tt/1qM0sTN
via IFTTT

Compliance with adjuvant capecitabine in patients with stage II and III colon cancer: comparison of administrative versus medical record data

Abstract

We aimed to examine the frequency of treatment delays as well as the reasons and appropriateness of such delays in early stage colon cancer patients receiving adjuvant capecitabine by comparing data from pharmacy dispensing versus medical records. Patients diagnosed with stage II or III colon cancer from 2008 to 2012 and who received at least two cycle of adjuvant capecitabine were reviewed for treatment delays. Data from pharmacy dispensing and patient medical records were compared. Multivariate regression models were constructed to identify predictors of treatment delays. A total of 697 patients were analyzed: median age was 70 years (IQR 30–89), 394 (57%) were men, 598 (86%) reported Eastern Cooperative Oncology Group 0/1, and 191 (27%) had stage II disease. In this study cohort, 396 (57%) patients experienced at least 1 treatment delay during their adjuvant treatment. Upon medical record review, half of treatment delays identified using pharmacy administrative data were actually attributable to side effects, of which over 90% were considered clinically appropriate for patients to withhold rather than to continue the drug. The most prevalent side effects were hand-foot syndrome and diarrhea which occurred in 176 (44%) and 67 (17%) patients, respectively. Multivariate analysis revealed a statistically significant association between stage and inappropriate treatment delays whereby patients with stage II disease were more likely to experience drug noncompliance (OR 1.79, 95% CI: 1.27–2.53, P < 0.001) than those with stage III disease. Compliance with adjuvant capecitabine was reasonable. Adherence ascertained from pharmacy administrative data differs significantly from that obtained from medical records.

Compliance with adjuvant capecitabine is reasonable in a population-based cohort of stage II and III colon cancer. However, adherence patterns ascertained from pharmacy administrative data differ significantly from those obtained from medical records.

from Cancer via ola Kala on Inoreader http://ift.tt/1qM16As
via IFTTT

Does Notch play a tumor suppressor role across diverse squamous cell carcinomas?

Abstract

The role of Notch pathway in tumorigenesis is highly variable. It can be tumor suppressive or pro-oncogenic, typically depending on the cellular context. Squamous cell carcinoma (SCC) is a cancer of the squamous cell, which can occur in diverse human tissues. SCCs are one of the most frequent human malignancies for which the pathologic mechanisms remain elusive. Recent genomic analysis of diverse SCCs identified marked levels of mutations in NOTCH1, implicating Notch signaling pathways in the pathogenesis of SCCs. In this review, evidences highlighting NOTCH's role in different types of SCCs are summarized. Moreover, based on accumulating structural information of the NOTCH receptor, the functional consequences of NOTCH1 gene mutations identified from diverse SCCs are analyzed, emphasizing loss of function of Notch in these cancers. Finally, we discuss the convergent view on an intriguing possibility that Notch may function as tumor suppressor in SCCs across different tissues. These mechanistic insights into Notch signaling pathways will help to guide the research of SCCs and development of therapeutic strategies for these cancers.

In this article, we discuss the convergent view on an intriguing possibility that Notch may function as a tumor suppressor in squamous cell carcinoma (SCC) across different tissues. These mechanistic insights into Notch signaling pathways will help to guide the research of SCCs and development of therapeutic strategies for these cancers.

from Cancer via ola Kala on Inoreader http://ift.tt/1P0L7u1
via IFTTT

E3 Ubiquitin ligase RNF126 regulates the progression of tongue cancer

Abstract

This study aims to analyze the role of RNF126 in the oncogenesis of tongue cancer. The cell proliferation and viability of human tongue cancer cells, SCC25 and SCC9 cells, were determined by cell counting and MTT assay, respectively. The effect of RNF126 on regulating AKT signaling pathway was analyzed through western blotting. The transplantation tumor model of nude mice was used to evaluate the tumorigenecity of RNF126. Knockdown of RNF126 inhibited the proliferation and viability of SCC9 and SCC25 cells. Inhibition of RNF126 also decreased the activity of AKT1 as well as its downstream molecules. Furthermore, RNF126 regulated the tumor volume on mice model. These data suggested that RNF126 might be related to the progression of tongue cancer through regulating AKT signaling pathway.

Our data suggested that RNF126 might be related to the progression of tongue cancer through regulating AKT signaling pathway.

from Cancer via ola Kala on Inoreader http://ift.tt/1qM0o6i
via IFTTT

Prognostic potential of the MDM2 309T>G polymorphism in stage I lung adenocarcinoma

Abstract

The MDM2 protein plays an important role in the regulation of cell proliferation and apoptosis via ubiquitination and proteasome-mediated degradation of p53. The genetic polymorphism rs2279744 (c.309T>G) of the MDM2 gene is reportedly associated with susceptibility and/or prognosis in various cancers. In this study, we investigated the risk factors for worse survival in patients with lung adenocarcinoma (AC). We examined the association between c.309T>G and the prognosis of lung cancer by retrospectively reviewing 453 lung cancer patients. We studied both, clinicopathological and genetic characteristics, including the c.309T>G, p53 Arg72Pro, EGFR, KRAS, and p53 mutations. Associations between these factors and survival outcome were analyzed using Cox proportional hazards models. The frequencies of MDM2 polymorphisms were T/T, 20.8%; T/G, 48.6%, and G/G, 30.7%. The overall survival (OS) of AC patients with pathological stage I disease and the MDM2 T/T genotype was significantly shorter than that of those with the T/G or G/G genotypes (P = 0.02). Multivariate analysis revealed that the MDM2 T/T genotype was an independent, significant prognostic factor (hazard ratio [HR] = 2.23; 95% confidence interval [CI]: 1.07–4.65; P = 0.03). The MDM2 T/T genotype was predictive of poorer survival in a Japanese population. Genotyping for this polymorphism might predict the clinical outcomes of stage I AC patients.

We examined the association between the c.309T>G polymorphisms of the MDM2 gene and lung cancer prognosis in 453 lung cancer patients. The MDM2 T/T genotype was an independent, significant prognostic factor (hazard ratio [HR] = 2.23; 95% confidence interval [CI]: 1.07–4.65; P = 0.03) for pathological stage I adenocarcinoma patients.

from Cancer via ola Kala on Inoreader http://ift.tt/1P0KLTX
via IFTTT

Measured cardiorespiratory fitness and self-reported physical activity: associations with cancer risk and death in a long-term prospective cohort study

Abstract

Physical activity is inversely associated with risk of some cancers. The relation with cancer-specific death remains uncertain. Mainly, studies on relationships between physical activity and cancer are based on self-reported physical activity (SPA). Hereby, we examined whether measured cardiorespiratory fitness (CRF) is associated with cancer risk, mortality, and case fatality. We also describe relationships between SPA and these outcomes, and between CRF and SPA. A cohort of 1997 healthy Norwegian men, aged 40–59 years at inclusion in 1972–75, was followed throughout 2012. At baseline, CRF was objectively measured. SPA (leisure time and occupational) was obtained through a questionnaire. Relationships between CRF or SPA, and the outcomes were estimated using Cox regression, adjusted for age, body mass index (BMI), and smoking. Pearson correlation coefficients evaluated agreements between CRF and SPA. During follow-up, 758 men were diagnosed with cancer and 433 cancer deaths occurred. Analyses revealed lower cancer risk (Hazard ratio [HR] 0.85, 95% confidence intervals [CI]: 0.68–1.00), mortality (HR 0.68, 95% CI: 0.53–0.88), and case fatality (HR 0.74, 95% CI: 0.57–0.96), in men with high CRF compared to low CRF. Light leisure time SPA was associated with lower cancer risk (HR 0.70, 95% CI: 0.56–0.86) and mortality (HR 0.64 95% CI: 0.49–0.83), whereas strenuous occupational SPA was associated with higher risks (HR 1.42, 95% CI: 1.13–1.78 and HR 1.45, 95% CI: 1.09–1.93). Correlations between CRF and SPA were 0.351 (P < 0.001) and −0.106 (P < 0.001) for leisure time and occupational SPA, respectively. A high midlife CRF may be beneficial for cancer risk, cancer mortality, and case fatality.

Little is known about the impact of physical fitness on cancer development. In this 40-year follow-up, a high baseline cardiorespiratory fitness (CRF) was associated with reduced risk of cancer, cancer mortality, and case fatality, indicating a beneficial role of high CRF in cancer development. The relations found for self-reported physical activity (SPA) and its correlation with CRF indicate that SPA may be biased.

from Cancer via ola Kala on Inoreader http://ift.tt/1qM1dfk
via IFTTT

Comparison of qualitative and semiquantitative strain elastography in breast lesions for diagnostic accuracy

Abstract

Background

Strain elastography can be purely qualitative or semiquantitative using both strain score and strain ratio. The aim of this study was to establish the accuracy of semiquantitative elastography using both strain score and strain ratio in differentiating benign from malignant breast masses. The diagnostic performance of the two methods was analysed for any statistically significant difference.

Methods

A prospective study was carried out from May to December 2014 in the University of Nairobi, Department of Diagnostic Imaging and Radiation Medicine. One hundred and eighteen patients referred for breast ultrasound following clinical detection of masses certified the inclusion criteria. All solid masses identified on grey scale imaging were subjected to strain elastography. Elastographic findings were represented in both strain score and strain ratio. Comparison of diagnostic performance with histological findings as the gold standard for all detected solid masses was done. Fisher's exact test and receiver operating characteristics curves were applied for statistical analysis to look for any significant differences between the diagnostic performance of strain score and strain ratio.

Results

Out of the 118, three patients did not attend for all the examinations and three biopsy results were misplaced therefore analysis was done for 112 subjects. The sensitivity, specificity, positive predictive value and negative predictive value of elasticity strain (Ueno) score were 0.86, 0.96, 0.89 and 0.96 respectively. For the strain ratio the values were 0.93, 0.96, 0.90 and 0.96 respectively. Fisher's exact test P values comparing the sensitivity and specificity were 0.69 and 1.00 respectively not considered significant at p 0.05 levels. The areas under the curve (AUCs) from the receiver operating characteristic (ROC) curves were 0.972 and 0.976 for strain score and ratio respectively with a strong Pearson's correlation coefficient, r 0.79 indicating a high diagnostic accuracy for both methods but no statistically significant difference in performance.

Conclusion

Semiquantitative ultrasound elastography has good diagnostic accuracy in differentiating benign and malignant breast solid lesions and there is no statistically significant difference between strain score and strain ratio in sensitivity, specificity and accuracy.

from Cancer via ola Kala on Inoreader http://ift.tt/22qtwxU
via IFTTT

Patient perspectives of a diagnosis of myeloproliferative neoplasm in a case control study

Abstract

Background

Myeloproliferative neoplasms (MPNs) including the classic entities; polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis are rare diseases with unknown aetiology. The MOSAICC study, is an exploratory case–control study in which information was collected through telephone questionnaires and medical records.

Methods

As part of the study, 106 patients with MPN were asked about their perceived diagnosis and replies correlated with their haematologist's diagnosis. For the first time, a patient perspective on their MPN diagnosis and classification was obtained. Logistic regression analyses were utilised to evaluate the role of variables in whether or not a patient reported their diagnosis during interview with co-adjustment for these variables. Chi square tests were used to investigate the association between MPN subtype and patient reported categorisation of MPN.

Results

Overall, 77.4 % of patients reported a diagnosis of MPN. Of those, 39.6 % recognised MPN as a 'blood condition', 23.6 % recognised MPN as a 'cancer' and 13.2 % acknowledged MPN as an 'other medical condition'. There was minimal overlap between the categories. Patients with PV were more likely than those with ET to report their disease as a 'blood condition'. ET patients were significantly more likely than PV patients not to report their condition at all. Patients from a single centre were more likely to report their diagnosis as MPN while age, educational status, and WHO re-classification had no effect.

Conclusions

The discrepancy between concepts of MPN in patients could result from differing patient interest in their condition, varying information conveyed by treating hematologists, concealment due to denial or financial concerns. Explanations for the differences in patient perception of the nature of their disease, requires further, larger scale investigation.

from Cancer via ola Kala on Inoreader http://ift.tt/1TGRem9
via IFTTT

Elevated MTSS1 expression associated with metastasis and poor prognosis of residual hepatitis B-related hepatocellular carcinoma

Abstract

Background

Methods

An orthotopic nude mice model with palliative HCC hepatectomy was performed in this study. Metastasis-related genes in tumor following resection were screened; HCC invasion, metastasis, and some molecular alterations were examined in vivo and in vitro. Clinical significance of key gene mRNA expression was also analyzed.

Results

Metastasis suppressor 1 (MTSS1) located in the central position of gene function net of residual HCC. MTSS1 was up-regulated in residual tumor after palliative resection. In hepatitis B-related HCC patients undergone palliative hepatectomy, those with higher MTSS1 mRNA expression accompanied by activation of matrix metalloproteinase 2 (MMP2) in residual HCC, had earlier residual HCC detection after hepatectomy and poorer survival when compared to those with lower MTSS1. In different cell lines, the levels of MTSS1 mRNA increased in parallel with metastatic potential. MTSS1 down regulation via siRNA decreased MMP2 activity, reduced invasive potentials of HCC by 28.9 % in vitro, and averted the deteriorated lung metastatic extent in vivo.

Conclusions

The poor prognosis of hepatitis B-related HCC patients following palliative hepatectomy associates with elevated MTSS1 mRNA expression; therefore, MTSS1 may provide a new research field for HCC diagnosis and treatment.

from Cancer via ola Kala on Inoreader http://ift.tt/1WWRLEw
via IFTTT

A case of multicentric gliomas in both supra- and infratentorial regions with different histology: a case report

Abstract

Background

Multicentric gliomas are well-separated tumors in different locations of the brain, without anatomical continuity between lesions. We report a rare case of multicentric gliomas that occurred in both supra- and infratentorial regions with different histopathology.

Case presentation

A 27-year-old man was admitted to our hospital with mild motor weakness of the right leg. Magnetic resonance imaging (MRI) showed a large tumor occupying the left insula, extending to the left basal ganglia, so tumor resection was performed. Histological diagnosis was diffuse astrocytoma. Tumor cells showed sporadic immunoreactivity for p53 and negative immunostaining for epidermal growth factor receptor (EGFR). Postoperative course was uneventful, and adjuvant therapy was not performed. At 7 months after surgery, MRI disclosed a left cerebellar tumor displaying an irregular ring formation on enhancement with gadolinium (Gd) and marked peritumoral edema. MRI studies including T2-weighted imaging demonstrated that this paravermian tumor had no contact with the initial left insular tumor. In addition, MRI studies of the whole neuraxis, cytological examination of the cerebrospinal fluid, and neurological findings demonstrated that no dissemination had occurred through the subarachnoid space or as intracerebral metastases. Therefore, the second surgery was performed. Histological diagnosis was glioblastoma. Immunohistochemistry revealed that most tumor cells were positively stained for both p53 and EGFR but negatively stained for isocitrate dehydrogenase 1 (IDH1).

Conclusions

We reported a case of multicentric gliomas occurring in both supra- and infratentorial regions with different histopathology. Immunohistochemical examinations suggest that different genetic pathways may participate in the occurrence of these tumors.

from Cancer via ola Kala on Inoreader http://ift.tt/1Z36Lhm
via IFTTT

Damage effect of high-intensity focused ultrasound on breast cancer tissues and their vascularities

Abstract

Background

High-intensity focused ultrasound (HIFU) is a noninvasive therapy that makes entire coagulative necrosis of a tumor in deep tissue through the intact skin. There are many reports about the HIFU's efficacy in the treatment of patients with breast cancer, but randomized clinical trials are rare which emphasize on the systematic assessment of histological changes in the ablated tumor vascularities, while clinical trials utilizing bevacizumab and other anti-angiogenic drugs in breast cancer have not demonstrated overall survival benefit. The purpose of this study is to evaluate the damage effect of HIFU on breast cancer tissues and their vascularities.

Methods

Randomized clinical trials and the modality of treat-and-resect protocols were adopted. The treated outcome of all patients was followed up in this study. The target lesions of 25 breast cancer patients treated by HIFU were observed after autopsy. One slide was used for hematoxylin-eosin (HE) staining, one slide was used for elastic fiber staining by Victoria blue and Ponceau's histochemical staining, and one slide was used for vascular endothelial cell immunohistochemical staining with biotinylated-ulex europaeus agglutinin I (UEAI); all three slides were observed under an optical microscopic. One additional slide was systematically observed by electron microscopy.

Results

The average follow-up time was 12 months; no local recurrence or a distant metastatic lesion was detected among treated patients. Histological examination of the HE slides indicated that HIFU caused coagulative necrosis in the tumor tissues and their vascularities: all feeder vessels less than 2 mm in diameter in the insonated tumor were occluded, the vascular elasticity provided by fibrin was lost, the cells were disordered and delaminated, and UEAI staining of the target lesions was negative. Immediately after HIFU irradiation, the tumor capillary ultrastructure was destroyed, the capillary endothelium was disintegrated, the peritubular cells were cavitated, and the plasma membrane was incomplete.

Conclusions

HIFU ablation can destroy all proliferating tumor cells and their growing vascularities simultaneously; this may break interdependent vicious cycle of tumor angiogenesis and neoplastic cell growth that results in infinite proliferation. While it cannot cause tumor resistance to HIFU ablation, it may be a new anti-angiogenic strategy that needs further clinical observation and exploration. Furthermore, the treatment indications of HIFU ablation were reviewed and discussed in this manuscript.

from Cancer via ola Kala on Inoreader http://ift.tt/1NPVkZP
via IFTTT

Prognostic Value of Vascular Invasion in Pediatric Osteosarcomas

Abstract

Metastatic status, histologic response, and quality of surgical resection are prognostic factors for osteosarcomas. Pathology reports sometimes describe peritumoral vascular invasion on surgical specimens after neoadjuvant chemotherapy but their prognostic significance as an independent parameter has never been reported. The aim of this study was to evaluate how the presence of this peritumoral vascular invasion could influence survival. We retrospectively analyzed histology, demographics, and outcomes of pediatric patients treated for osteosarcoma in our institutions between January 2007 and December 2012. A single pathologist analyzed the resection specimens after neoadjuvant chemotherapy. Fifty-one osteosarcomas were diagnosed over a 6-year period; nine had metastatic disease at diagnosis. Surgery was performed after neoadjuvant chemotherapy in all cases. We identified peritumoral vascular invasion in the surgical specimens in 15 cases. Two-year event-free survival (EFS) was 78 % (CI95%[64;93]) for patients without vascular invasion versus 48 % (CI95% [21;75]) in patients with vascular invasion, and 2-year overall survival (OS) was 94 % (CI95%[86;100]) for those without vascular invasion versus 79 % (CI95%[57;100]) for others. Multivariate analysis demonstrated correlation of metastatic status and presence of vascular invasion with survival. The histopathological description of peritumoral vascular invasion in surgical specimens of osteosarcoma after neoadjuvant chemotherapy can be considered a prognostic factor and could indicate modification of the postoperative therapeutic strategy.

from Cancer via ola Kala on Inoreader http://ift.tt/1qLpwtR
via IFTTT

Essential role of miRNAs in orchestrating the biology of the tumor microenvironment

Abstract

MicroRNAs (miRNAs) are emerging as central players in shaping the biology of the Tumor Microenvironment (TME). They do so both by modulating their expression levels within the different cells of the TME and by being shuttled among different cell populations within exosomes and other extracellular vesicles. This review focuses on the state-of-the-art knowledge of the role of miRNAs in the complexity of the TME and highlights limitations and challenges in the field. A better understanding of the mechanisms of action of these fascinating micro molecules will lead to the development of new therapeutic weapons and most importantly, to an improvement in the clinical outcome of cancer patients.

from Cancer via ola Kala on Inoreader http://ift.tt/1qLIEYU
via IFTTT

Renal atrophy after stereotactic body radiotherapy for renal cell carcinoma

Abstract

Background

Renal atrophy is observed in an irradiated kidney. The aim of this study was to determine dose-volume histogram parameters and other factors that predict renal atrophy after 10-fraction stereotactic body radiotherapy (SBRT) for primary renal cell carcinoma (RCC).

Methods

A total of 14 patients (11 males, 3 females) who received SBRT for RCC at Tohoku University Hospital between April 2010 and February 2014 were analyzed. The median serum creatinine level was 1.1 mg/dl and two patients had a single kidney. Nine patients were implanted with fiducial markers. The median tumor diameter was 30 mm. SBRT was delivered at 70 Gy in 10 fractions for 7 tumors, at 60 Gy in 10 fractions for 2 tumors, and at 50 Gy in 10 fractions for 5 tumors with 6 and/or 15 MV X-ray using 5 to 8 multi-static beams. Renal atrophy was assessed using post-SBRT CT images after 12–24 months intervals. Correlations were examined by Spearman rank correlation analysis. Differences between two groups were evaluated by the Mann-Whitney test, and pairwise comparisons were made by the Wilcoxon signed-rank test.

Results

The median tumor volume shrunk from 14.8 cc to 10.6 cc (p = 0.12), and the median irradiated kidney volume changed from 160.4 cc to 137.1 cc (p < .01). The median peak creatinine level was 1.6 mg/dl after treatment (p < .01). Percentage volumes of the irradiated kidney receiving at least 10 Gy (V₁₀, p = 0.03), V₂₀ (p < .01), V₃₀(p < .01), V₄₀ (p = 0.01), mean irradiated kidney dose (p < .01), and magnitude of overlap between PTV and kidney volume (p = 0.03) were significantly correlated with post-treatment irradiated kidney volume in percent, and V₂₀-V₃₀ had strong correlation (r < −0.70, p < .01). Patients with implanted fiducial markers showed a significantly lower ratio of renal atrophy (p = 0.02).

Conclusions

Significant renal atrophic change was observed. Dose distribution of SBRT at 20–30 Gy had a strong correlation with renal atrophy when irradiation was performed in 10 fractions.

from Cancer via ola Kala on Inoreader http://ift.tt/1TGHBUs
via IFTTT

Integration of 68 Ga-PSMA-PET imaging in planning of primary definitive radiotherapy in prostate cancer: a retrospective study

Abstract

Background

Prostate cancer (PC) is one of the most commonly treated cancer entities with radiation therapy (RT). Risk group-adapted treatment and avoidance of unnecessary toxicities relies primarily on accurate tumor staging. Thus, the introduction of prostate-specific membrane antigen (PSMA) in diagnosis and treatment of PC is a highly interesting development in radiation oncology of urologic tumors. The present work is to evaluate the integration of ⁶⁸Ga-PSMA-PET imaging into standard radiation planning of primary definitive treatment of PC and to determine the impact of PSMA imaging on tumor staging.

Methods

The data of 15 patients treated for PC between August 2013 and April 2015 were evaluated. Treatment planning included ⁶⁸Ga-PSMA-PET imaging. We analyzed whether the use of PSMA-imaging led to a change of the TNM stage and if it influenced the RT treatment approach or the target volume, due to changes in the gross tumor volume (GTV) or clinical target volume (CTV), in the final treatment plan.

Results

In 53.3 % of the analyzed patients a change occurred in the TNM stage based on ⁶⁸Ga-PSMA-PET examination. The RT concept changed in 33.3 % of all patients, leading to relevant changes in the planning target volume. Among these, an additional irradiation of the pelvic lymph drainage due to tracer uptake in lymph nodes was performed in 25 %. Furthermore, boost volumes of PET-positive lymph nodes were added in 80 % of these cases. A down staging due to the ⁶⁸Ga-PSMA-PET examination occurred in 13.3 % of all cases.

Conclusions

The integration of ⁶⁸Ga-PSMA-PET-imaging into the RT treatment planning process can be useful for detailed target volume planning. The performance of a ⁶⁸Ga-PSMA-PET frequently leads to changes in the TNM stage, altering the RT treatment regimen and the target volume. A prospective trial is underway to evaluate the impact of ⁶⁸Ga-PSMA-PET based treatment planning on outcome.

from Cancer via ola Kala on Inoreader http://ift.tt/27TVDtk
via IFTTT

Racial and ethnic differences in patient navigation: Results from the Patient Navigation Research Program

cover.gif?v=1&s=93db58289553c94229dd6cc9

BACKGROUND

Patient navigation was developed to address barriers to timely care and reduce cancer disparities. The current study explored navigation and racial and ethnic differences in time to the diagnostic resolution of a cancer screening abnormality.

METHODS

The authors conducted an analysis of the multisite Patient Navigation Research Program. Participants with an abnormal cancer screening test were allocated to either navigation or control. The unadjusted median time to resolution was calculated for each racial and ethnic group by navigation and control. Multivariable Cox proportional hazards models were fit, adjusting for sex, age, cancer abnormality type, and health insurance and stratifying by center of care.

RESULTS

Among a sample of 7514 participants, 29% were non-Hispanic white, 43% were Hispanic, and 28% were black. In the control group, black individuals were found to have a longer median time to diagnostic resolution (108 days) compared with non-Hispanic white individuals (65 days) or Hispanic individuals (68 days) (P<.0001). In the navigated groups, black individuals had a reduction in the median time to diagnostic resolution (97 days) (P<.0001). In the multivariable models, among controls, black race was found to be associated with an increased delay to diagnostic resolution (hazard ratio, 0.77; 95% confidence interval, 0.69-0.84) compared with non-Hispanic white individuals, which was reduced in the navigated arm (hazard ratio, 0.85; 95% confidence interval, 0.77-0.94).

CONCLUSIONS

Patient navigation appears to have the greatest impact among black patients, who had the greatest delays in care. Cancer 2016. © 2016 American Cancer Society.

from Cancer via ola Kala on Inoreader http://ift.tt/1WWz8AE
via IFTTT

Tumor-associated macrophages induce capillary morphogenesis of lymphatic endothelial cells derived from human gastric cancer

cover.gif?v=1&s=f91fefbdc718461b9cc88f43

Abstract

Tumor lymphangiogenesis is a major prognostic indicator of gastric cancer. Tumor-induced inflammation has been shown to attract tumor-associated macrophages (TAMs) that affect lymphangiogenesis. However, detailed mechanisms of macrophage-induced lymphangiogenesis have not been elucidated. Here, we evaluated the interaction between TAMs and lymphatic endothelial cells (LECs) derived from lymph nodes (LNs) of human gastric cancer. LECs were directly or indirectly co-cultured with macrophages from healthy human blood, with or without the supernatant of the gastric cancer cell line, OCUM-12. We analyzed the effect of cancer pretreated macrophages and of macrophages from metastatic LNs of gastric cancer on LECs. We observed morphological changes of LECs in co-culture and assessed the gene expression of possible lymphangiogenic molecules of macrophages and LECs after contact co-culture, and of cancer pretreated macrophages, by qRT-PCR. Specimens of metastatic LN of gastric cancer were immunofluorescently stained. We found that tubulogenesis of LECs was observed only in the contact co-culture model. OCUM-12 cells promoted macrophage-induced tubulogenesis of LECs. Relative gene expression of matrix metalloproteinases (MMP) and adhesion molecules was significantly up-regulated in both capillary-forming LECs and co-cultured macrophages. Cancer pretreated macrophages up-regulated lymphangiogenic factors including inflammatory cytokines, MMPs, adhesion molecules and VEGF-C. Blocking of ICAM-1 and macrophage activation suppressed tubulogenesis of LECs. Immunohistochemistry showed macrophages localized around lymphatic vessels. Our results suggested that interaction between LECs and macrophages may be an important initial step of tumor lymphangiogenesis developing LN metastasis. Understanding of its mechanisms could be useful for future therapeutics of gastric cancer.

from Cancer via ola Kala on Inoreader http://ift.tt/1P0b2Sp
via IFTTT

Dynamic changes in immune cell profile in head and neck squamous cell carcinoma: immunomodulatory effects of chemotherapy

cover.gif?v=1&s=f91fefbdc718461b9cc88f43

Abstract

Tumor cells have evolved sophisticated means of escape from the host immune system. To date, several important immunological phenomena have been demonstrated in peripheral blood as well as within tumors. In the present study, we firstly investigated the proportion and activation status of peripheral immune regulatory cells and CD8⁺ T cell subsets in patients with head and neck squamous cell carcinoma (HNSCC) using a multicolor flow cytometer, and then evaluated how TPF (docetaxel, cisplatin, and 5-fluorouracil) therapy modulated the immune cell profile in peripheral blood. The proportion of naïve T cells was lower and that of effector memory T cells (T_EM) cells was higher in HNSCC patients than in healthy donors. Moreover, the proportions of activated T_EM and effector T cells (T_EFF) were dramatically increased in patients with advanced stage disease. The proportion of regulatory T cells and CD14⁺ HLA-DR^- myeloid-derived suppressor cells was elevated in HNSCC patients. Of note, after TPF therapy, besides the transient reduction in immune regulatory cells, decreases in central memory T cells (T_CM) and increases in T_EFF cells were observed among CD8⁺ T-cell subsets, suggesting differentiation from T_CM cells into T_EFF cells. Our results suggested that despite the immunosuppressive status in HNSCC patients, tumor-specific immune responses mediated by CD8⁺ T cells might be induced and maintained. Moreover, chemotherapy can trigger not only a transient reduction in immune regulatory cells but also further activation of CD8⁺ T cells.

from Cancer via ola Kala on Inoreader http://ift.tt/1qLAIH7
via IFTTT

Yin Yang 1 is associated with cancer stem cell transcription factors (SOX2, OCT4, BMI1) and clinical implication

The transcription factor Yin Yang 1 (YY1) is frequently overexpressed in cancerous tissues compared to normal tissues and has regulatory roles in cell proliferation, cell viability, epithelial-mesenchymal tran...

from Cancer via ola Kala on Inoreader http://ift.tt/1NPESc4
via IFTTT

Macroscopic Hematuria after Conventional or Hypofractionated Radiotherapy: Results from a Prospective Phase III Study

Publication date: Available online 25 May 2016
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Giuseppe Sanguineti, Fabio Arcidiacono, Valeria Landoni, Bianca Maria Saracino, Alessia Farneti, Stefano Arcangeli, Maria Grazia Petrongari, Sara Gomellini, Lidia Strigari, Giorgio Arcangeli
PurposeTo assess macroscopic hematuria rates within a single institution randomized phase III trial comparing dose escalated, conventionally fractionated radiotherapy (CFRT) vs moderately hypofractionated RT (MHRT) for localized prostate cancer.Methods and MaterialsPatients with intermediate to high risk localized prostate cancer were treated with conformal radiotherapy and short-course androgen deprivation. Both the prostate and the entire seminal vesicles were treated to 80 Gy in 40 fractions over 8 weeks (CFRT) or 62 Gy in 20 fractions over 5 weeks (MHRT). The endpoint of this study is the development of any episode/grade of macroscopic hematuria. Median follow-up is 93 months (range: 6-143 months).ResultsMacroscopic hematuria was reported by 25/168 (14.9%) patients. The actuarial estimate of hematuria at 8 yrs is 17.0% (95%CI: 10.7%-23.3%). The number of patients with hematuria was 6 vs 19 in the CFRT and MHRT arms, respectively, for an actuarial 8-yr estimate of 9.7% and 24.3% (HR: 3.468, 95%CI: 1.385-8.684, p=0.008). Overall, 8/25 patients were found to have a biopsy-proven urothelial carcinoma (CFRT: 3 pts; MHRT: 5 pts, p=0.27). Nevertheless, the 8-yr actuarial incidence of macroscopic hematuria (after censoring urothelial cancer-related episodes) was 4.1% and 18.2% after CFRT and MHRT, respectively (HR: 4.961, 95%CI: 1.426-17.263, p=0.012). The results were confirmed at multivariate analysis after taking into account several patient, treatment and tumor related covariates.ConclusionMHRT is associated with a statistically significant increased risk of macroscopic hematuria over CFRT.

Teaser

Despite favorable radiobiologic expectations, the present study shows that moderate hypofractionation was associated with a significantly higher incidence of macroscopic hematuria than conventionally fractionated radiotherapy for localized prostate cancer within a prospective randomized trial.

from Cancer via ola Kala on Inoreader http://ift.tt/1Wm0jnS
via IFTTT

"Asian Pac J Cancer Prev"[jour]; +121 new citations

121 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Asian Pac J Cancer Prev"[jour]

These pubmed results were generated on 2016/05/26

PubMed comprises more than 24 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

from Cancer via ola Kala on Inoreader http://ift.tt/1U9c62u
via IFTTT

Renal atrophy after stereotactic body radiotherapy for renal cell carcinoma

Renal atrophy is observed in an irradiated kidney. The aim of this study was to determine dose-volume histogram parameters and other factors that predict renal atrophy after 10-fraction stereotactic body radio...

from Cancer via ola Kala on Inoreader http://ift.tt/1TGeD6Y
via IFTTT

The dosimetric impact of implants on the spinal cord dose during stereotactic body radiotherapy

The effects of spinal implants on dose distribution have been studied for conformal treatment plans. However, the dosimetric impact of spinal implants in stereotactic body radiotherapy (SBRT) treatments has no...

from Cancer via ola Kala on Inoreader http://ift.tt/22q4DCm
via IFTTT

Expanding the Spectrum of ALK-Rearranged Renal Cell Carcinomas in Children: Identification of a Novel HOOK1-ALK Fusion Transcript

from Cancer via ola Kala on Inoreader http://ift.tt/20FYrVr
via IFTTT

BRCA1-2 Diagnostic Workflow From NGS to Variant Identification and Final Report

Abstract

The BRCA1-BRCA2 genes predispose to hereditary breast and ovarian cancer, and the germline and mutational status of these genes defines a target population that can benefit from PARP inhibitor treatments. To respond to the increasing number of BRCA1-BRCA2 tests, it is necessary to shift to high throughput technologies that are reliable and less time consuming. Different methodological platforms are dedicated to this purpose with different approaches and algorithms for analysis. Our aim was to set up a cost-effective and low time consuming BRCA1-BRCA2 mutation detection workﬂow using the Ion Torrent PGM technology. A retrospective cohort of 40 familial breast/ovarian cancer patients previously tested by Sanger sequencing and a prospective cohort of 72 patients (validation set) were analyzed. The validation set included 64 patients affected by familial breast/ovarian cancer and eight sporadic ovarian cancer cases, who are potential candidates for PARPi treatments. A complete and standardized workflow easily usable and suitable in a certified laboratory has been proved and validated. This includes all steps from library preparation to the final report. The use of next generation sequencing will be of benefit for patients enrolled in the genetic counselling process and, moreover, will enhance the process of selecting patients eligible for personalized treatments. This article is protected by copyright. All rights reserved.

from Cancer via ola Kala on Inoreader http://ift.tt/1sclU5v
via IFTTT

Concerns underlying treatment preferences of advanced cancer patients with children

Abstract

Background

Decision-making about advanced cancer treatment is complex and may be influenced by patients' family context, including the presence of children.

We explored how parental values and concerns motivate patients' preferences about aggressiveness of advanced cancer treatment as well as preferences for palliative care and hospice services.

Methods

We conducted semi-structured interviews with 42 patients with advanced cancer who had at least one child under 18 years. We created and applied thematic codes. Descriptive analyses were used to report the number of participants who mentioned each code.

Results

The majority of participants (29/42) reported that having children influenced their preferences for advanced cancer care. For most parents, extending life to maximize the time they had left to parent their children was important in guiding treatment preferences. Others prioritized preserving their physical condition and parental functioning and remaining physically close to their children. Many parents discussed life extension and parental functioning preservation as competing priorities. Most of the sample expressed interest in palliative care services and hospice, but responses by several participants reflected concerns about dying at home and lack of clarity about the role of early palliative care.

Conclusions

Parents in our sample expressed that maximizing time with their children and preserving parental functioning were important concerns underlying their preferences for advanced cancer care. Future research should assess the palliative and end-of-life care needs and preferences of parents with advanced cancer, which may differ from those of non-parents. Copyright © 2016 John Wiley & Sons, Ltd.

from Cancer via ola Kala on Inoreader http://ift.tt/20FYOiE
via IFTTT

High rate of thiamine deficiency among inpatients with cancer referred for psychiatric consultation: results of a single site prevalence study

Abstract

Objective

Thiamine deficiency (TD) is increasingly recognized in medically ill patients. The prevalence of TD among cancer patients is unknown. This study aims to characterize the prevalence of TD among inpatients with cancer.

Methods

Retrospective chart review of patients admitted to a large cancer center who were referred for psychiatric consultation and whose serum thiamine concentration was measured. Patients with alcohol use were excluded.

Results

Among 217 patients with various cancer types, TD was found in 55.3%. Risk factors included fluorouracil-based chemotherapy, significant weight loss, and undergoing active cancer treatment. Almost all patients were normal weight, overweight, or obese, and few had concomitant vitamin B12 or folate deficiency. A total of 17.5% were receiving multivitamin supplementation. Nearly half (49.8%) did not receive empiric treatment with thiamine and among those who did, treatment delay occurred in the majority of cases (59.6%). Measurement of serum thiamine concentration preceded psychiatric consultation in only 10.6% of cases.

Conclusions

Our findings suggest that TD is highly prevalent among inpatients with cancer, even among normal and overweight individuals, in the absence of other vitamin deficiencies, and while receiving multivitamin supplements. Several potential risk factors were identified, including active cancer treatment. Evaluation of TD was most commonly not initiated by oncologists. Failure to treat and treatment delay were common. Given these findings, oncologists must be vigilant about detecting TD among inpatients with cancer. Copyright © 2016 John Wiley & Sons, Ltd.

from Cancer via ola Kala on Inoreader http://ift.tt/1scmrEL
via IFTTT

The relevance of experiential avoidance in breast cancer distress: insights from a psychological group intervention

Abstract

Background

Research on the implication of experiential avoidance in the aetiology and maintenance of diverse forms of psychopathology has grown considerably over the last 10 years. However, the potential contribution of experiential avoidance to cancer-related distress has received limited attention. Accordingly, the objective of this study was to examine the association between experiential avoidance, symptoms of anxiety and depression, and quality of life (QoL) during the course of a psychological group intervention for women with breast cancer.

Methods

Fifty-four women with breast cancer participated in a psychological group intervention designed to reduce distress and improve QoL. Participants completed measures of experiential avoidance, anxiety and depressive symptoms, and QoL upon the first and last sessions.

Results

A path analysis revealed that, after controlling for baseline measures, smaller reductions in experiential avoidance during the course of the intervention predicted smaller reductions in anxiety and depressive symptoms. Also, experiential avoidance had a negative indirect effect on QoL via depressive symptoms.

Conclusions

Experiential avoidance may perpetuate the emotional problems commonly found in women with breast cancer and attenuate improvements associated with participation in psychological interventions. Implications for clinical practice in psycho-oncology are discussed. Copyright © 2016 John Wiley & Sons, Ltd.

from Cancer via ola Kala on Inoreader http://ift.tt/20FYQag
via IFTTT

MAGE-A1–6 expression in patients with head and neck squamous cell carcinoma: impact on clinical patterns and oncologic outcomes

Abstract

Background

Various subtypes of melanoma-associated antigens (MAGEs) are expressed in the tumor tissues of patients with head and neck squamous cell carcinoma (HNSCC). However, little data are currently available on how the gene expression of MAGEs impacts clinical patterns and oncologic outcomes. We have therefore evaluated the expression of MAGE-A1–6 (A1–6) subtypes in tumor tissues of patients with HNSCC and the clinical impact of this expression.

Methods

This was a retrospective review of 53 patients with histologically proven HNSCC of the oral cavity, oropharynx, larynx, or hypopharynx who underwent both treatment and analysis by reverse transcription (RT)-PCR assay with a common primer to identify the expression of MAGE-A1–6 subtypes in the tumor tissue. The clinicopathologic factors and oncologic outcomes of these patients and the correlations of both to MAGE-A1–6 gene expression were analyzed.

Results

MAGE-A1–6 subtypes were expressed in the tumor tissues of 37 patients (69.8 %). Patient age of ≥65 years [p = 0.031, hazard ratio (HR) 4.866] and advanced American Joint Committee on Cancer stage (p = 0.035, HR 4.291) were independent risk factors for expression of MAGE-A1–6 subtypes. Patients with MAGE-A1–6 expression had lower disease-free survival (p = 0.029), disease-specific survival (p = 0.070), and overall survival (p = 0.017) rates. Overall survival rate was independently associated to chemotherapy (p = 0.011, HR 2.859), while no surgery (p = 0.050, HR 2.400) and MAGE-A1–6 expression (p = 0.050, HR 2.527) showed borderline significance.

Conclusion

In our patient group the expression of MAGE-A1–6 subtypes in tumor tissues of patients with HNSCC was correlated with advanced clinical stage of cancer and poor oncologic outcomes. We suggest that gene expression of MAGE-A1–6 subtypes may be considered to be a predictive factor to determine patient treatment or follow-up strategy.

from Cancer via ola Kala on Inoreader http://ift.tt/1NPkQyw
via IFTTT

Association of atopic diseases and parvovirus B19 with acute lymphoblastic leukemia in childhood and adolescence in the northeast of Brazil

Abstract

Background

Several factors related to the immune system, such as a history of allergies and virus infections, may be associated with acute lymphoblastic leukemia (ALL). The purpose of this study was to analyze whether the presence of atopic diseases and previous infection with parvovirus B19 and Epstein−Barr virus (EBV) are associated with the development of ALL.

Methods

This case–control study was performed in two tertiary hospitals located in northeastern Brazil. The study population included 60 patients who were diagnosed with non-T-cell ALL using myelogram and immunophenotyping and 120 patients in the control group. Atopy was evaluated via a parent questionnaire and medical records. Total immunoglobulin (Ig)E and IgG levels of parvovirus B19 and EBV were measured in the serum. Logistic regression was performed to assess the association between variables and odds of ALL.

Results

We identified a significant inverse association between rhinitis, urticaria and elevated IgE serum levels with ALL. A history of parvovirus B19 infection showed a significant association with this type of cancer [OR (95 % CI) 2.00 (1.94–4.26); P = 0.050]. In logistic regression, the presence of atopy was a protective factor [OR (95 % CI) 0.57 (0.38–0.83); P = 0.004], and the presence of IgG for parvovirus B19 was an important risk factor for ALL [OR (95 % CI) 2.20 (1.02–4.76); P = 0.043].

Conclusions

These results suggest that atopic diseases and elevated total IgE levels are associated with a potential protective effect on the development of ALL. Previous infection with parvovirus B19 contributed to ALL susceptibility.

from Cancer via ola Kala on Inoreader http://ift.tt/20FIIWq
via IFTTT

The prognostic significance of specific HOX gene expression patterns in ovarian cancer

Abstract

HOX genes are vital for all aspects of mammalian growth and differentiation, and their dysregulated expression is related to ovarian carcinogenesis. The aim of the current study was to establish the prognostic value of HOX dysregulation as well as its role in platinum resistance. The potential to target HOX proteins through the HOX/PBX interaction was also explored in the context of platinum resistance. HOX gene expression was determined in ovarian cancer cell lines and primary EOCs by QPCR, and compared to expression in normal ovarian epithelium and fallopian tube tissue samples. Statistical analysis included one-way ANOVA and t-tests, using statistical software R and GraphPad. The analysis identified 36 of the 39 HOX genes as being overexpressed in high grade serous EOC compared to normal tissue. We detected a molecular HOX gene-signature that predicted poor outcome. Overexpression of HOXB4 and HOXB9 was identified in high grade serous cell lines after platinum resistance developed. Targeting the HOX/PBX dimer with the HXR9 peptide enhanced the cytotoxicity of cisplatin in platinum-resistant ovarian cancer. In conclusion, this study has shown the HOX genes are highly dysregulated in ovarian cancer with high expression of HOXA13, B6, C13, D1 and D13 being predictive of poor clinical outcome. Targeting the HOX/PBX dimer in platinum–resistant cancer represents a potentially new therapeutic option that should be further developed and tested in clinical trials. This article is protected by copyright. All rights reserved.

from Cancer via ola Kala on Inoreader http://ift.tt/20FDhXp
via IFTTT

Role of ATG10 expression quantitative trait loci in non-small cell lung cancer survival

Abstract

To evaluate whether genetic variants in autophagy-related genes affect the overall survival (OS) of non-small cell lung cancer (NSCLC) patients. We analyzed 14 single nucleotide polymorphisms (SNPs) in core autophagy-related genes for OS in 1001 NSCLC patients. Three promising SNPs in ATG10 were subsequently annotated by the expression quantitative trait loci (eQTL) and methylation quantitative trait loci (meQTL) analyses based on Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) datasets. We observed that the variants of rs10514231, rs1864182 and rs1864183 were associated with poor lung cancer survival (HR = 1.33, 95% CI = 1.07-1.65; HR = 1.43, 95%CI = 1.13-1.81; HR = 1.38, 95%CI = 1.14-1.68, respectively) and positively correlated with ATG10 expression (all P <0.05) from GTEx and TCGA datasets. The elevated expression of ATG10 may predict shorter survival time in lung cancer patients in TCGA dataset (HR = 2.10, 95%CI = 1.33-3.29). Moreover, the variants of rs10514231 and rs1864182 were associated with the increased methylation levels of cg17942617 (meQTL), which in turn contributed to the elevated ATG10 expression and decreased survival time. Further functional assays revealed that ATG10 facilitated lung cancer cell proliferation and migration. Our findings suggest that eQTL/meQTL variations of ATG10 could influence lung cancer survival through regulating ATG10 expression. This article is protected by copyright. All rights reserved.

from Cancer via ola Kala on Inoreader http://ift.tt/25nvRPg
via IFTTT

Assessing the role of insulin-like growth factors and binding proteins in prostate cancer using Mendelian randomization: Genetic variants as instruments for circulating levels

Abstract

Circulating insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) are associated with prostate cancer. Using genetic variants as instruments for IGF peptides, we investigated whether these associations are likely to be causal.

We identified from the literature 56 single nucleotide polymorphisms (SNPs) in the IGF axis previously associated with biomarker levels (8 from a genome-wide association study [GWAS] and 48 in reported candidate genes). In ∼700 men without prostate cancer and two replication cohorts (N∼900 and ∼9,000), we examined the properties of these SNPS as instrumental variables (IVs) for IGF-I, IGF-II, IGFBP-2 and IGFBP-3. Those confirmed as strong IVs were tested for association with prostate cancer risk, low (< 7) vs high (≥ 7) Gleason grade, localised vs advanced stage, and mortality, in 22,936 controls and 22,992 cases. IV analysis was used in an attempt to estimate the causal effect of circulating IGF peptides on prostate cancer.

Published SNPs in the IGFBP1/IGFBP3 gene region, particularly rs11977526, were strong instruments for IGF-II and IGFBP-3, less so for IGF-I. Rs11977526 was associated with high (vs low) Gleason grade (OR per IGF-II/IGFBP-3 level-raising allele 1.05; 95% CI 1.00, 1.10). Using rs11977526 as an IV we estimated the causal effect of a one SD increase in IGF-II (∼265 ng/ml) on risk of high vs low grade disease as 1.14 (95% CI 1.00, 1.31).

Because of the potential for pleiotropy of the genetic instruments, these findings can only causally implicate the IGF pathway in general, not any one specific biomarker. This article is protected by copyright. All rights reserved.

from Cancer via ola Kala on Inoreader http://ift.tt/20FEbmO
via IFTTT

Molecular correlates and prognostic value of tmTNF-α expression in colorectal cancer of 5-Fluorouracil-Based Adjuvant Therapy.

Molecular correlates and prognostic value of tmTNF-α expression in colorectal cancer of 5-Fluorouracil-Based Adjuvant Therapy.

Cancer Biol Ther. 2016 May 25;:0

Authors: Li X, Wang S, Ren H, Ma J, Sun X, Li N, Liu C, Huang K, Xu M, Ming L

Abstract
Transmembrane tumor necrosis factor-α (tmTNF-α) is known to induce the activation of NF-κB to protect tumor cells. Upregulation of tmTNF-α leads to resistance to apoptosis and induces drug resistance in breast cancer. However, the expression of tmTNF-α in colorectal cancer (CRC) and its association with clinical outcome in CRC have remained unclear. In this study, we examined the tmTNF-α expression in CRC by immunohistochemistry and western blotting, assessed the prognostic value of tmTNF-α related to the recurrence/metastasis and survival of stage II/III CRC by the Kaplan-Meier survival curve and Cox regression model, and also explored the role of tmTNF-α expression on the chemotherapeutic efficacy of 5-Fluorouracil by flow cytometry assay and cell counting kit-8 (CCK-8) in vitro. Overall, we found that 77 (78.6%) out of 98 patients exhibited higher tmTNF-α expression in the CRC tissues comparing with the adjacent tissues. The tmTNF-α expression was correlated with Differentiation (P = 0.019), TNM stage (P = 0.039), Lymph nodes metastasis (P = 0.024) and Lymphovascular invasion (P = 0.027) but not related with Age (P = 0.617), Gender (P = 0.625), Tumor location (P = 0.138), Perforation/Obstruction (P = 1.000), Depth of invasion (P = 0.327), and microsatellite instability status (P = 0.150). The prognostic analyses showed that high tmTNF-α expression patients was significantly associated with decreased Disease-Free Survival (P = 0.0209) and Overall Survival (P = 0.0163). CCK-8 results suggested that the tmTNF-α influenced the chemotherapeutic effect of 5-Fluorouracil on colon cancer cells. Altogether, these data indicated the stage II/III CRC patients with high tmTNF-α expression were more likely to have a worse prognosis than patients with low tmTNF-α expression and tmTNF-α may influence the chemotherapeutic effect of 5-Fluorouracil. The mechanism for these observations warrants further study.

PMID: 27224726 [PubMed - as supplied by publisher]

from Cancer via ola Kala on Inoreader http://ift.tt/1OZvwLa
via IFTTT

Molecular correlates and prognostic value of tmTNF-α expression in colorectal cancer of 5-Fluorouracil-Based Adjuvant Therapy.

Molecular correlates and prognostic value of tmTNF-α expression in colorectal cancer of 5-Fluorouracil-Based Adjuvant Therapy.

Cancer Biol Ther. 2016 May 25;:0

Authors: Li X, Wang S, Ren H, Ma J, Sun X, Li N, Liu C, Huang K, Xu M, Ming L

PMID: 27224726 [PubMed - as supplied by publisher]

from Cancer via ola Kala on Inoreader http://ift.tt/1OZvwLa
via IFTTT

Molecular correlates and prognostic value of tmTNF-α expression in colorectal cancer of 5-Fluorouracil-Based Adjuvant Therapy.

Molecular correlates and prognostic value of tmTNF-α expression in colorectal cancer of 5-Fluorouracil-Based Adjuvant Therapy.

Cancer Biol Ther. 2016 May 25;:0

Authors: Li X, Wang S, Ren H, Ma J, Sun X, Li N, Liu C, Huang K, Xu M, Ming L

PMID: 27224726 [PubMed - as supplied by publisher]

from Cancer via ola Kala on Inoreader http://ift.tt/1OZvwLa
via IFTTT