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Cancer Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174
Κυριακή 20 Δεκεμβρίου 2015
Ophthalmic epidemiology in Europe: the “European Eye Epidemiology” (E3) consortium
Abstract
The European Eye Epidemiology (E3) consortium is a recently formed consortium of 29 groups from 12 European countries. It already comprises 21 population-based studies and 20 other studies (case–control, cases only, randomized trials), providing ophthalmological data on approximately 170,000 European participants. The aim of the consortium is to promote and sustain collaboration and sharing of data and knowledge in the field of ophthalmic epidemiology in Europe, with particular focus on the harmonization of methods for future research, estimation and projection of frequency and impact of visual outcomes in European populations (including temporal trends and European subregions), identification of risk factors and pathways for eye diseases (lifestyle, vascular and metabolic factors, genetics, epigenetics and biomarkers) and development and validation of prediction models for eye diseases. Coordinating these existing data will allow a detailed study of the risk factors and consequences of eye diseases and visual impairment, including study of international geographical variation which is not possible in individual studies. It is expected that collaborative work on these existing data will provide additional knowledge, despite the fact that the risk factors and the methods for collecting them differ somewhat among the participating studies. Most studies also include biobanks of various biological samples, which will enable identification of biomarkers to detect and predict occurrence and progression of eye diseases. This article outlines the rationale of the consortium, its design and presents a summary of the methodology.
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Prolonged second stage of labor is associated with low Apgar score
Abstract
There is no consensus on the effects of a prolonged second stage of labor on neonatal outcomes. In this large Swedish population-based cohort study, our objective was to investigate prolonged second stage and risk of low Apgar score at 5 min. All nulliparous women (n = 32,796) delivering a live born singleton infant in cephalic presentation at ≥37 completed weeks after spontaneous onset of labor between 2008 and 2012 in the counties of Stockholm and Gotland were included. Data were obtained from computerized records. Exposure was time from fully retracted cervix until delivery. Logistic regression analyses were used to estimate crude and adjusted odds ratios (ORs) with 95 % confidence intervals (CIs). Adjustments were made for maternal age, height, BMI, smoking, sex, gestational age, sex-specific birth weight for gestational age and head circumference. Epidural analgesia was included in a second model. The primary outcome measure was Apgar score at 5 min <7 and <4. We found that the overall rates of 5 min Apgar score <7 and <4 were 7.0 and 1.3 per 1000 births, respectively. Compared to women with <1 h from retracted cervix to birth, adjusted ORs of Apgar score <7 at 5 min generally increased with length of second stage of labor: 1 to <2 h: OR 1.78 (95 % CI 1.19–2.66); 2 to <3 h: OR 1.66 (1.05–2.62); 3 to <4 h: OR 2.08 (1.29–3.35); and ≥4 h: OR 2.71 (1.67–4.40). We conclude that prolonged second stage of labor is associated with an increased risk of low 5 min Apgar score.
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Pre-gravid oral contraceptive use in relation to birth weight: a prospective cohort study
Abstract
Few studies have evaluated the association between pregravid oral contraceptive (OC) use and birth weight, and findings have been conflicting. We conducted a prospective cohort study of 5921 pregnancy planners in Denmark to evaluate recency, duration, and type of OC used before conception in relation to infant birth weight. Participants completed online questionnaires and reported detailed information on contraceptive history and covariates at baseline. Participants completed bimonthly follow-up questionnaires to update their pregnancy status for up to 12 months or until conception occurred. Birth weight data were ascertained from the Danish Medical Birth Registry for 4046 live births delivered by study participants between 2008 and 2010. We used multivariable linear and log-binomial regression analyses to control for confounding. Mean birth weight was higher among women who had used OCs within 0–1 months (mean difference = 97 g, CI 26, 168) or 2–6 months (mean difference = 40 g, CI −5, 85) before conception, compared with more than 12 months before conception. Mean birth weight was lower among women who had used OCs for long durations (mean difference comparing ≥12 with <4 years of OC use = −85 g, CI −158, −11). Our findings indicate that pregravid OC use within 6 months of conception may be associated with a small increase in birth weight, but that long duration of use may have the opposite effect. Results were stronger among male infants, among 2nd and 4th generation OC users, and among users of OCs with a higher estrogen dose.
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Physician experiences and preferences in the treatment of HR+/HER2− metastatic breast cancer in the United States: a physician survey
Abstract
Sequential endocrine therapy (ET) is recommended for postmenopausal women with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) metastatic breast cancer (mBC) and without visceral symptoms. Chemotherapy (CT) can be considered after sequential ETs, but is associated with adverse side effects. We assessed physicians' preferences and self-reported prescribing patterns for ET and CT in the treatment of HR+/HER2− mBC at community practices in the United States. Community-based oncologists/hematologists from a nationwide online panel who treated postmenopausal women with HR+/HER2− mBC were invited to complete a survey, blinded to the identity of study sponsor. Treatment preferences were collected by treatment class of ET-based regimens versus CT and by agent for postmenopausal HR+/HER2− mBC patients after prior nonsteroidal aromatase inhibitor use in the adjuvant or mBC setting. Among 213 physicians who completed the survey, 78% were male, 71% were based in small/intermediate practices (2–9 oncologists/subspecialists), 55% had >10 years of experience, and 58% referred to the National Comprehensive Cancer Network Guidelines when treating mBC. Among first-line ETs, anastrozole was the most frequently used treatment (35%), followed by everolimus-based (EVE, 34%) and fulvestrant-based (FUL, 15%) therapy. After first-line ET, the most preferred second- and third-line treatments were ET monotherapy (48% and 39%), ET combination therapy (31% and 19%), and CT monotherapy (13% and 30%). Comparing EVE versus FUL, physicians preferred EVE in all lines but first line. Efficacy was the most important consideration for treatment choice. Physicians prescribed CT in early lines mainly because of visceral symptoms. This survey of treatment patterns for HR+/HER2− mBC in community practice suggested that after first-line ET, ET mono- or combination therapy was commonly used for the second- and third-line treatments and CT monotherapy for third- or later line treatments. CTs were used in early lines for patients with visceral symptoms.
A total of 213 physicians reported prescribing patterns for endocrine therapy and chemotherapy (CT) in the treatment of hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) metastatic breast cancer (mBC) at community practices in the United States. The National Comprehensive Cancer Network Guidelines were the most important reference source for the treatment of HR+/HER2− mBC, and physicians used, in the order of preference, anastrozole, everolimus-based, and fulvestrant-based endocrine therapies for the first-line treatment of mBC. The most preferred second-line treatments were endocrine monotherapy or combination therapy, and CT monotherapy was mainly used in the third- or later lines.
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Communication and US-Somali Immigrant Human Papillomavirus (HPV) Vaccine Decision-Making
Abstract
The current study uses a multiple goal theoretical perspective to explore how Somali immigrant families living in Ohio, USA, make decisions regarding whether to vaccinate their children against human papillomavirus (HPV)—a leading cause of cervical cancer. A focus was placed on the communication goals of parents in HPV vaccine discussions with their child and health care provider. Semi-structured interviews were audiotaped, transcribed, and analyzed using a grounded theory approach. Key themes are the implications of the vaccine for early sexual activity, confusion between HPV and HIV (human immunodeficiency virus), the perception that the HPV vaccine is unnecessary, uncertainty about the vaccine's efficacy and side effects, avoidance of parent-child communication about the vaccine, and a preference for framing the vaccine as a health promotion behavior. Framing the threat of HPV in the context of initiation of sexual activity, uncertainty regarding vaccine efficacy, and anticipated regret account for the inconsistency in HPV vaccine uptake among Somali parents. Clinicians should consider talking about HPV as a distal versus an immediate threat and HPV vaccine uptake as a health-promotion behavior rather than a sexually transmitted infection prevention behavior.
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Checking In on Cancer Checkpoint Inhibitors
Earlier this year, former U.S. President Jimmy Carter announced that he was undergoing treatment for advanced melanoma that included the immunotherapy drug pembrolizumab (Keytruda®)—part of a class of drugs known as checkpoint inhibitors. He recently reported that his most recent MRI scan did not reveal any signs of the original cancer or any new tumors.
In this interview, James Gulley, M.D., Ph.D., head of the Immunotherapy Section in the Genitourinary Malignancy Branch of NCI's Center for Cancer Research and director of the Center's Medical Oncology Service, discusses checkpoint inhibitors, their impact on patient care, and future directions for these therapies.
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Ophthalmic epidemiology in Europe: the “European Eye Epidemiology” (E3) consortium
Abstract
The European Eye Epidemiology (E3) consortium is a recently formed consortium of 29 groups from 12 European countries. It already comprises 21 population-based studies and 20 other studies (case–control, cases only, randomized trials), providing ophthalmological data on approximately 170,000 European participants. The aim of the consortium is to promote and sustain collaboration and sharing of data and knowledge in the field of ophthalmic epidemiology in Europe, with particular focus on the harmonization of methods for future research, estimation and projection of frequency and impact of visual outcomes in European populations (including temporal trends and European subregions), identification of risk factors and pathways for eye diseases (lifestyle, vascular and metabolic factors, genetics, epigenetics and biomarkers) and development and validation of prediction models for eye diseases. Coordinating these existing data will allow a detailed study of the risk factors and consequences of eye diseases and visual impairment, including study of international geographical variation which is not possible in individual studies. It is expected that collaborative work on these existing data will provide additional knowledge, despite the fact that the risk factors and the methods for collecting them differ somewhat among the participating studies. Most studies also include biobanks of various biological samples, which will enable identification of biomarkers to detect and predict occurrence and progression of eye diseases. This article outlines the rationale of the consortium, its design and presents a summary of the methodology.
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Circulating U2 small nuclear RNA fragments as a diagnostic and prognostic biomarker in lung cancer patients
Abstract
Purpose
Lung cancer accounts for one in five cancer deaths. Broad screening strategies for high-risk populations are unavailable, and the validation of biomarkers for early cancer detection remains a prime interest. Therefore, we investigated the value of circulating U2 small nuclear RNA fragments (RNU2-1f) as a biomarker for diagnosis, prognosis estimation and treatment monitoring in a large lung cancer cohort.
Methods
We determined RNU2-1f abundance in sera of patients with treatment-naive lung cancer (n = 211, 25.6 % early stage), chronic lung disease (n = 56) and healthy controls (n = 58) by reverse transcription quantitative PCR. Initial levels and changes after one chemotherapy cycle were correlated with treatment outcomes in patient subsets.
Results
Relative serum RNU2-1f expression levels (REL) were elevated in lung cancer patients compared with patients with chronic lung disease and healthy controls (p < 0.0001). The area under the receiver operating characteristic curve for the complete data set (lung cancer vs. healthy) was 0.91 (95 % CI 0.87–0.95). By applying a REL of −4.505 as diagnostic cutoff (Youden's criterion), sensitivity and specificity reached 0.86 and 0.81, respectively. To determine the generalization error, in a subsampling study, sensitivity and specificity were estimated as 0.82 and 0.77 for the application to future, independent samples. High initial RNU2-1f REL were associated with shorter median survival in stage IIIB/IV disease (RNU2-1fhigh = 228 days/RNU2-1flow = 484 days; p = 0.009, log-rank test, HR1.43 95 % CI 1.23–1.66). Multivariate analysis confirmed RNU2-1f as an independent prognostic factor. Patients with subsequent RNU2-1f reduction had a trend toward better treatment outcome.
Conclusions
Serum RNU2-1f may serve as a biomarker for lung cancer detection, prognosis prediction and treatment monitoring.
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Molecular Characterization of an Endometrial Endometrioid Adenocarcinoma Metastatic to a Thyroid Hürthle Cell Adenoma Showing Cancerization of Follicles
Abstract
Tumor-to-tumor metastasis is rare. Herein, we present a unique case of endometrial endometrioid adenocarcinoma metastatic to a thyroid Hürthle cell adenoma 9 years after initial diagnosis. On histologic examination of the thyroid, the malignant endometrioid glands and single cells (donor tumor) were dispersed within the Hürthle cell adenoma (recipient tumor). In several sections of the adenoma with still preserved microfollicular architecture, malignant endometrial adenocarcinoma cells were admixed within oncocytic adenomatous epithelium (so-called "cancerization of the follicles"). This unusual phenomenon, to our knowledge, is a novel finding in the thyroid gland. Immunohistochemistry, subsequently elicited clinical history, and morphologic comparison of the tumor in the thyroid to the primary endometrial tumor confirmed the origin of the donor tumor cells. Molecular analysis of both the metastatic and primary endometrial tumors demonstrated PIK3CA and PTEN mutations in both tumors, as is characteristic of well-differentiated endometrioid tumors of the endometrium. Amplification of chromosome 1q was detected in both sites; however, only the metastatic tumor showed loss of chromosomes 2, 9, and 22. The morphologic differential diagnosis of metastatic endometrioid adenocarcinoma in the thyroid includes columnar cell variant of papillary thyroid carcinoma (CCVPTC) arising in a preexisting adenoma, endocrine glandular atypia within an adenoma, and metastasis from other anatomic sites. Histomorphologic differences among these entities may be subtle; therefore, knowledge of and morphologic comparison with prior malignancies and immunohistochemistry can be helpful in rendering the correct diagnosis.
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IL-1 in Colon Inflammation, Colon Carcinogenesis and Invasiveness of Colon Cancer
Abstract
Interleukin-1 (IL-1) is a major "alarm" upstream pro-inflammatory cytokine that mainly acts by inducing cascades of cytokine and inflammation-promoting mediators. In the tumor arena, IL-1 is produced by both malignant and microenvironmental cells. IL-1α and IL-1β are the major agonists of IL-1, while IL-1Ra is a physiological inhibitor of pre-formed IL-1. IL-1α and IL-1β differ in their compartmentalization and in the producing cells. IL-1β is only active in its inflammasome dependent processed and secreted form and has been considered as the major mediator of inflammation. On the other hand, IL-1α is mainly cell-associated in tissue resident cells, being also active in its precursor form. The role of the IL-1 molecules in the unique microenvironment in the colon is largely unknown. Here, we described the role of IL-1α and IL-1β in colon homeostasis, colon inflammation, colon carcinogenesis and invasiveness of colorectal cancer. Understanding of the integrative role of IL-1α and IL-1β in these processes will facilitate the application of novel IL-1 modulating approaches.
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A phase I trial of ANG1/2-Tie2 inhibitor trebaninib (AMG386) and temsirolimus in advanced solid tumors (PJC008/NCI♯9041)
Summary
Background There is crosstalk between the ANG-Tie2 and the PI3K/Akt/mTOR pathways. Combined ANG1/2 and mTOR blockade may have additive anti-cancer activity. The combination of trebananib, an inhibitor of ANG1/2-Tie2 interaction, with temsirolimus was evaluated in patients with advanced solid tumors to determine tolerability, maximum tolerated dose (MTD), and preliminary antitumor activity. Methods Patients were enrolled using 3 + 3 design, and were given intravenous trebananib and temsirolimus on Day 1, 8, 15 and 22 of a 28-day cycle. Dose limiting toxicities (DLTs) were evaluated during cycle 1. Peripheral blood was collected for evaluation of Tie2-expressing monocytes (TEMs) and thymidine phosphorylase (TP). Sparse pharmacokinetic (PK) sampling for trebananib drug levels was performed on Day 1 and 8 of cycle 2. Results Twenty-one patients were enrolled, 6 at dose level (DL) 1, 7 at DL −1, and 8 at DL −2. No effect of temsirolimus on trebananib PK was observed. The most common treatment-related adverse events (AEs) were: fatigue (81 %), edema (62 %), anorexia (57 %), nausea (52 %), rash (43 %) and mucositis (43 %). The most common grade ≥ 3 AEs included lymphopenia (28 %) and fatigue (28 %). The MTD was exceeded at DL-2. Of 18 response evaluable patients, 1 partial response was observed (ER+/HER2−/PIK3CA mutant breast cancer) and 4 patients had prolonged SD ≥ 24 weeks. No correlation with clinical benefit was observed with change in number TEMs or TP expression in TEMs with treatment. Conclusions The MTD was exceeded at trebananib 10 mg/kg weekly and temsirolimus 20 mg weekly, with frequent overlapping toxicities including fatigue, edema, and anorexia.
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Content of Selected Minerals and Active Ingredients in Teas Containing Yerba Mate and Rooibos
Abstract
The study aimed to determine the content of selected elements: sodium, potassium, copper, zinc, iron, manganese and active ingredients such as phenolic acids and tannins in teas containing Yerba Mate and Rooibos cultivated in various areas. The study material comprised six samples of Yerba Mate teas and of Rooibos teas, both tea bags and leaves, purchased in Puławy and online via Allegro. In total, 24 samples were tested. Yerba Mate was particularly abundant in Mn and Fe. The richest source of these elements was Yerba Mate Yer-Vita (2261.3 mg · kg−1 d.m.) and (691.6 mg · kg−1 d.m.). The highest content of zinc was determined in Yerba Mate Amanda with lime (106.0 mg · kg−1 d.m.), while copper was most abundant in Yerba Mate Big-Active cocoa and vanilla (14.05 mg · kg−1 d.m.). In Rooibos, the content of sodium was several times higher than in Yerba Mate. A clear difference was observed in the content of minerals in dry weight of the examined products, which could be a result of both the taxonomic distinctness and the origin of the raw material. Leaf teas turned out to be a better source of tannins; on the other hand, tea bags contained substantially more phenolic acids. The richest source of phenolic acids was Yer-Vita in bags (1.8 %), and the highest amount of tannins was recorded in the leaf tea Green Goucho caramel and dark chocolate (9.04 g · 100 g−1 d.m.). In Rooibos products, the highest content of phenolic acids was recorded in tea bags (Savannah with honey and vanilla 0.96 %), and tannins in (Lord Nelson with strawberry and cream 7.99 g · 100 g −1 d.m.).
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Study of the Annexin A1 and Its Associations with Carcinoembryonic Antigen and Mismatch Repair Proteins in Colorectal Cancer
Abstract
Purpose
Annexin-A1 (ANXA1) has been implicated in various tumor types, but few studies have investigated its involvement in colorectal cancer. The study aimed to analyze ANXA1 expression in the normal margin and colorectal tumor tissues of 104 patients who underwent surgery for colorectal cancer and to associate the ANXA1 expression with predictive clinicopathological variables.
Methods
Hematoxylin-eosin and immunohistochemical staining were used for the analysis.
Results
ANXA1 expression was higher in colorectal cancer than in normal margin tissue (p = 0.0001). However, no differences were observed when we analyzed the ANXA1 expression in colon and rectal tumors (p = 0.830). Also, this protein positivity was associated with increased carcinoembryonic antigen levels (p = 0.004). Our data in the DNA-mismatch repair proteins expression was in accordance to the literature. And their positivity was not associated with ANXA1 presence in colorectal cancer.
Conclusion
The high incidence of ANXA1 positive expression in colorectal cancer and its association with carcinoembryonic antigen levels might indicate the importance of this protein in the colorectal cancer biology.
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Association of Methylenetetrahydrafolate Reductase Gene Polymorphism (MTHFR) in Patients with Gallbladder Cancer
Abstract
Purpose
5,10-Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in folate metabolism and plays a major role in DNA methylation. There are two popular MTHFR polymorphisms known as C677T and A1298C which are found to be involved in folate metabolism and lowering the enzyme activity, thus may be linked with cancer development. This study aims to look at the association of these polymorphisms in gallbladder cancer.
Methods
Thirty patients each with gallbladder cancer, cholelithiasis, and normal gallbladder were genotyped for the above-given polymorphisms by PCR-restriction fragment length polymorphism (RFLP) method.
Results
C677T MTHFR polymorphism was not associated (χ 2 = 2.44, p = 0.85) with an increased likelihood of having gallbladder cancer. A1298C was significantly associated (χ 2 = 28.87, p < 0.001) with risk of developing gallbladder cancer. A1298C was significantly correlated with grade (r = 0.337, p < 0.001) and histopathology (r = 0.446, p < 0.001).
Conclusion
This study proposed that MTHFR A1298C polymorphism may be associated with risk of developing gallbladder cancer, and there is no association between C677T polymorphism and gallbladder cancer.
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Motion and Volumetric Change as Demonstrated by 4DCT: The Effects of Abdominal Compression on the GTV, Lungs & Heart in Lung Cancer Patients
Publication date: Available online 19 December 2015
Source:Practical Radiation Oncology
Author(s): Abdullah Rasheed, Salma K. Jabbour, Stephen Rosenberg, Ajay Patel, Sharad Goyal, Bruce G. Haffty, Ning J. Yue, Alvin Khan
PurposeLung tumors move during respiration, complicating radiotherapy. The abdominal compression plate (ACP) is thought to reduce respiratory motion. This study quantifies ACP efficacy on respiratory-induced motion by using 4DCT to evaluate volume and displacement changes of the heart, lungs, and tumor with and without ACP.Methods and MaterialsLung cancer patients (n=17) received 4DCT simulations (10 CTs from 0%-90% breathing phases) with and without ACP under maximally tolerated diaphragmatic pressure. Gross tumor volume (GTV), heart and lungs were contoured in treatment planning software for each phase. Structures were exported for analysis. For each phase, with and without ACP, tumor and organ absolute centroid range of motion (ROM) and volume were calculated.ResultsACP did not significantly affect GTV, heart, or lung motion on the sample as a whole, but instead demonstrated patient-specific results. ACP reduced GTV motion in 3 (17.6%; 3 upper lobe tumors) by 2.9mm (p<0.01), increased motion in 5 (29.4%; 3 upper lobe tumors, 1 middle lobe, 1 lower lobe) by 1.9mm (p<0.03), and did not significantly change 9. Of the 3 patients exhibiting significantly decreased GTV motion, GTV, heart and lung ROM was 7.4mm, 11.8mm, and 11.9mm, respectively, without compression and 4.5mm, 8.4mm, and 10.9mm, respectively, with compression. Averaged across the sample, ACP did not exhibit any axis-specific effect.ConclusionsACP efficacy was patient specific, possibly due to preexisting factors including COPD severity, chest wall elasticity, tumor location, and patient comfort. Tumor lobe location does not pre-determine compression efficacy; therefore, patients should be simulated with and without ACP, regardless of tumor location. GTV motion seems most important in determining suitability for compression. Alternative motion control should be considered in patients not benefited by compression. In patients who benefited, ACP may enhance tumor coverage while minimizing toxicity. Larger scale studies are necessary for definitive treatment recommendations.
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A Review of Clinical Studies and Practical Guide for the Administration of Triplet Chemotherapy Regimens with Bevacizumab in First-line Metastatic Colorectal Cancer
Abstract
Colorectal cancer is the third most common cancer worldwide. A significant proportion of patients presents with unresectable metastatic disease or develops metachronous metastases following surgical resection of the primary tumor. The prognosis of the disease has improved over the past two decades, with extended multimodality treatment options and the development of increasingly intensified chemotherapy regimens that now typically include targeted biologics. A recent advance in therapy is a treatment regimen composed of three chemotherapeutic agents (i.e., triplet chemotherapy: 5-fluorouracil [5-FU]/leucovorin [LV], oxaliplatin, and irinotecan; FOLFOXIRI) in combination with the vascular endothelial growth factor inhibitor bevacizumab. This regimen has been shown to elicit significantly improved objective response rates and median progression-free survival compared with 5-FU/LV and irinotecan in combination with bevacizumab. However, triplet chemotherapy has been associated with increased rates of chemotherapy-related adverse events, and treatment-emergent adverse events should be properly managed to minimize treatment interruption or discontinuation. We present herein a review of clinical studies evaluating the safety and efficacy of FOLFOXIRI with bevacizumab in metastatic colorectal cancer, and propose a practical guide for the management of adverse events associated with the regimen.
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Distinct health behavior and psychosocial profiles of young adult survivors of childhood cancers: a mixed methods study
Abstract
Background
We used a mixed-methods approach to examine health behavior profiles of young adult cancer survivors and characterize related sociodemographic and psychosocial factors.
Methods
We conducted a mail-based survey assessing sociodemographics, cancer treatment, health behaviors (e.g., tobacco use, physical activity), healthcare provider interactions, and psychosocial factors (e.g., Profile of Moods States [POMS]) among 106 young adult survivors from a southeastern cancer center and semi-structured interviews among a subset of 26.
Results
A k-means cluster analysis using eight health behaviors yielded three distinct health behavior profiles: high risk (n = 25), moderate risk (n = 39), and low risk (n = 40). High risks had the highest current alcohol, tobacco, and marijuana use; physical activity; and number of sexual partners (p's < 0.001). They had higher symptoms of POMS tension-anxiety, depression-dejection, fatigue-inertia, and confusion-bewilderment (p's < 0.05). Moderate risks had lowest physical activity (p < 0.05) but otherwise had moderate health behaviors. Low risks had the lowest alcohol, tobacco, and marijuana use and fewest sexual partners (p's < 0.05). They had the lowest levels of tension-anxiety, depression-dejection, fatigue-inertia, and confusion-bewilderment (p's < 0.05). Qualitative interviews showed that cancer had a range of effects on health behaviors and variable experiences regarding how healthcare providers address these behaviors.
Conclusions
Assessing health behavior profiles, rather than individual health behaviors, is informative in characterizing young adult cancer survivors and targeting survivorship care.
Implications for Cancer Survivors
Young adult cancer survivors demonstrate distinct health behavior profiles and are differentially impacted by the experience of cancer. Healthcare providers should be consistently intervening to ensure that survivors understand their specific health risks.
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The search for optimal cutoff points for apoptosis and proliferation rate in prognostification of early stage breast cancer patients treated with anthracyclines in adjuvant settings
Abstract
Cancer growth is determined by the proportion of proliferating to dying cells; thus, the aim of the study was to analyze how proliferation rate and apoptosis level affect disease-free survival (DFS) of breast cancer (BC) patients treated with anthracycline-based chemotherapy. For 172 BC, proliferation rate was investigated by Ki-67 labeling index (Ki-67 LI)-assessed immunohistochemically. Apoptosis level was analyzed by apoptotic index (AI) estimated by terminal deoxynucleotidyl transferase dUTP nick end labeling assay. To stratify patients into subgroups with higher and lower DFS and to achieve optimal categorization, optimal cutoff points were searching by minimal P value method. The best separation of DFS curves (P = 0.001) was observed for three categories of AI: (i) AI >1.8 % (DFS = 100 %), (ii) AI ≤0.3 % (DFS = 84.6 %), and (iii) 1.8 % <= AI >0.3 % (DFS = 64.0 %). The highest DFS (86.1 %) was shown for the subgroup with low-proliferating BC (Ki-67 LI ≤18.0 %), intermediate (73.9 %) for patients characterized by Ki-67 LI in the range 18.0–37.0 % and the lowest (60.0 %) for women with fast-proliferating tumors (Ki-67 LI >37.0 %) (P = 0.022). Summarized, minimal P value method allows for optimal separation of survival curves. Apoptosis level and proliferation rate have some prognostic potential for early stage breast cancer patients treated with anthracyclines in adjuvant setting, however, as suggested by multivariate analysis, not as independent prognostic factors.
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PTEN and p16 genes as epigenetic biomarkers in oral squamous cell carcinoma (OSCC): a study on south Indian population
Abstract
Phosphatase and tensin homolog (PTEN) and p16INK4a (p16) genes are tumor suppressor genes, associated with epigenetic alterations. PTEN and p16 promoter hypermethylation is a major epigenetic silencing mechanism leading to cancer. The cooperation between PTEN and p16 in pathogenesis of cancers suggest that their combination might be considered as potential molecular marker for specific subgroups of patients. Hence, the present study aimed to investigate whether PTEN and p16 promoter methylations were involved in oral squamous cell carcinoma (OSCC) in south Indian subjects. DNA methylation quantitative analyses of the two candidate tumor suppressor genes PTEN and p16 were performed by methylation-specific polymerase chain reaction (MSP). Fifty OSCC biopsy samples and their corresponding non-malignant portions as controls were studied comparatively. The methylation status was correlated with the clinical manifestations. Twelve out of 50 patients (24 %) were found to be methylated for PTEN gene, whereas methylation of the p16 gene occurred in 19 out of 50 cases (38 %). A statistically significant result was obtained (P = <0.0001 and 0.017) for both PTEN and p16 genes. PTEN and p16 promoter methylation may be the main mechanism leading to the low expression of PTEN and p16 genes indicating the progress of tumor development. Our data suggest that a low PTEN and p16 expression due to methylation may contribute to the cancer progression and could be useful for prognosis of OSCC. Therefore, analysis of promoter methylation in such genes may provide a biomarker valuable for early detection of oral cancer.
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MicroRNA-663 suppresses cell invasion and migration by targeting transforming growth factor beta 1 in papillary thyroid carcinoma
Abstract
MicroRNA-663 (miR-663) has been detected in a large variety of tumor types; however, it still holds both tumor suppressive and oncogenic roles in different tumor types. The miRNA-CHIP microarray assay revealed downregulation of miR-663 in papillary thyroid carcinoma (PTC); however, the effect of miR-663 on PTC cell invasion and migration remains unknown. Accordingly, this study aimed to investigate the potential involvement of miR-663 in PTC. In this study, miR-663 expression level was measured via quantitative real-time PCR in 91 pairs of human PTC and adjacent normal tissues and in two human PTC cell lines. The effect of miR-663 on PTC cell invasion and migration were studied by transwell and wound healing assays. In addition, the miR-663 target was searched and the underlying mechanism was clarified by reporter assay and rescue experiment. The current study confirmed that miR-663 expression was inhibited in PTC tissue samples and PTC cell lines. There were statistically significant differences in expression of miR-663 with regard to age and tumor size. Upregulation of miR-663 suppressed PTC cell invasion and migration. Further study showed that transforming growth factor beta 1 (TGFβ1) was the direct target of miR-663 and mediated the effect of miR-663 on PTC development. By targeting TGFβ1, miR-663 efficiently regulates the expression of epithelial-mesenchymal transition (EMT) markers and matrix metalloproteinases (MMPs). The data indicated that miR-663 may suppress tumor invasion and migration by targeting TGFβ1 and regulate EMT progress of PTC cells.
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Antibiotic drug tigecycline reduces neuroblastoma cells proliferation by inhibiting Akt activation in vitro and in vivo
Abstract
As the first member of glycylcycline bacteriostatic agents, tigecycline is approved as a novel expanded-spectrum antibiotic, which is clinically available. However, accumulating evidence indicated that tigecycline was provided with the potential application in cancer therapy. In this paper, tigecycline was shown to exert an anti-proliferative effect on neuroblastoma cell lines. Furthermore, it was found that tigecycline induced G1-phase cell cycle arrest instead of apoptosis by means of Akt pathway inhibition. In neuroblastoma cell lines, the Akt activator insulin-like growth factor-1 (hereafter referred to as IGF-1) reversed tigecycline-induced cell cycle arrest. Besides, tigecycline inhibited colony formation and suppressed neuroblastoma cells xenograft formation and growth. After tigecycline treatment in vivo, the Akt pathway inhibition was confirmed as well. Collectively, our data provided strong evidences that tigecycline inhibited neuroblastoma cells growth and proliferation through the Akt pathway inhibition in vitro and in vivo. In addition, these results were supported by previous studies concerning the application of tigecycline in human tumors treatment, suggesting that tigecycline might act as a potential candidate agent for neuroblastoma treatment.
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Oxymatrine synergistically enhances the inhibitory effect of 5-fluorouracil on hepatocellular carcinoma in vitro and in vivo
Abstract
Oxymatrine (OMT), one of the main active components of extracts from the dry roots of Sophora flavescens, has long been employed clinically to treat cancers. Here, we investigated the synergistic effect of OMT with 5-fluorouracil (5-Fu) on the tumor growth inhibition of hepatocellular carcinoma cells (HCC; Hep-G2 and SMMC-7721) and explored the underlying mechanism. Cells were treated with OMT and/or 5-Fu and subjected to cell viability, colony formation, apoptosis, cell cycle, western blotting, xenograft tumorigenicity assay, and immunohistochemistry. OMT and 5-Fu inhibited the proliferation of Hep-G2 and SMMC-7721 cells, and combination treatment with OMT and 5-Fu resulted in a combination index <1, indicating a synergistic effect. Co-treatment with OMT and 5-Fu caused G0/G1 phase arrest by upregulating P21 and P27 and downregulating cyclin D, and induced apoptosis through increasing the production of reactive oxygen species (ROS) and decreasing the levels of p-ERK. In addition, the inhibition of ROS respectively reversed the cell death induced by 5-Fu + OMT, suggesting the key roles of ROS in the process. More importantly, 5-Fu and OMT in combination exhibit much superior tumor weight and volume inhibition on SMMC-7721 xenograft mouse model in comparison to 5-Fu or OMT alone. Immunohistochemistry analysis suggests the combinations greatly suppressed tumor proliferation, which was consistent with our in vitro results. Taken together, our findings indicated that OMT sensitizes HCC to 5-Fu treatment by the suppression of ERK activation through the overproduction of ROS, and combination treatment with OMT and 5-Fu would be a promising therapeutic strategy for HCC treatment.
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Prognostic investigations of B7-H1 and B7-H4 expression levels as independent predictor markers of renal cell carcinoma
Abstract
In order to evaluate the correlation of B7-H4 and B7-H1 with renal cell carcinoma (RCC), we analyzed B7-H1 and B7-H4 expressions and their clinical significance by immunohistochemical method. Our result indicated that B7-H4-positive staining was detected in 58.13 % of RCC tissues (25 tissues tumors), and there were 18 tissues of patients without detectable B7-H4. Furthermore, 21 cases (48.83 %) were B7-H1-positive. Positive tumor expressions of B7-H4 and B7-H1 were markedly related to advanced TNM stage (P = 0.001; P = 0.014), high grade (P = 0.001; P = 002), and larger tumor size (P = 0.002; P = 024) in RCC tissues than patients with B7-H4-negative and B7-H1-negative in RCC tissues. The patients with B7-H1 and B7-H4-positive expressions were found to be markedly correlated with the overall survival of the patients (P < 0.05) and tended to have an increased risk of death when compared with negative expression groups. Univariate analysis showed that B7-H4 and B7-H1 expressions, TNM stage, high grade, and tumor size were significantly related to the prognosis of RCC. Furthermore, multivariate analysis showed that B7-H4 and B7-H1 expressions decreased overall survival. The adjusted HR for B7-H1 was 2.83 (95 % CI 1.210–2.971; P = 0.031) and also was 2.918 (95 % CI 1.243–3.102; P = 0.006) for B7-H4 that showed these markers were independent prognostic factors in RCC patients. The expressions of B7-H1 and B7-H4 in RCC patients indicate that these markers may be as a predictor of tumor development and death risk. Further investigations can be helpful to confirm B7-H1 and B7-H4 roles as an independent predictor of clinical RCC outcome.
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Resveratrol reduces IL-6 and VEGF secretion from co-cultured A549 lung cancer cells and adipose-derived mesenchymal stem cells
Abstract
Stem cell therapies are important treatment methodologies used in many areas of experimental or clinical medicine. In recent studies of cancer models, Mesenchymal stem cells (MSCs) suppressed the growth of cancer cells. However, also in some studies, stem cell treatments have been shown to induce cancer formation, increase tumor volume, induce the formation of new vessels, and lead to cancer invasion. The presence of MSC-secreted cytokines and their effects on cancer cells limits the reliability of MSC-based treatments. Resveratrol (trans-3,5,4′-trihydroxystilbene), an antioxidant found in red wine, has been shown to have therapeutic effects against several cancers. The aim of this study was to co-culture MSCs with A549 cancer cells to suppress the release of cancer-promoting cytokines from MSCs and to increase the applicability and reliability of stem cell therapies with resveratrol. MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and neutral red cell viability assays were used to find safety dose of resveratrol. The MSCs secreted the cytokines IL-6 and VEGF, and the effect of resveratrol on these cytokines was analyzed by ELISA and western blot analysis of conditioned medium. One μM of resveratrol was found to be the safety dose for the A549 cancer cells and MSCs. We observed the highest release of IL-6 and VEGF from the co-cultured A549 cells and MSCs, and resveratrol was found to significantly decrease the release of these cytokines. Our study suggests that resveratrol exerts a positive effect on the release of cytokines. The safety dose of resveratrol can be administered together with stem cells during stem cell treatment.
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Oleanolic acid inhibits cell survival and proliferation of prostate cancer cells in vitro and in vivo through the PI3K/Akt pathway
Abstract
Oleanolic acid (OA) is a naturally occurring pentacyclic triterpenoid and possesses diverse pharmacological activities, including anti-cancer effects that have been confirmed in multiple types of human cancers. However, the potential effect of natural OA on human prostate cancer is still unclear. The present study aimed to explore whether and how OA exerted anti-cancer effects in prostate cancer. Our data showed that OA inhibited cell viability and proliferation, and promoted cell apoptosis and G0/G1 phase cell cycle arrest in prostate cancer PC-3, DU145, and LNCaP cells, in a dose-dependent manner. In addition, OA was found to regulate the expression levels of apoptosis-related and cell cycle-related proteins, as well as the activity of PI3K/Akt pathway, in a dose-dependent manner. Mechanistically, our data revealed that OA exerted anti-cancer effects in vitro in PC-3 and DU145 cells by repressing the PI3K/Akt pathway. In agreement, OA also suppressed the tumor growth of PC-3 cells in vivo via inhibition of the PI3K/Akt pathway. In conclusion, our findings demonstrate the anti-cancer properties of OA in prostate cancer cells, both in vitro and in vivo, and provide the experimental evidence for the use of OA as an adjuvant agent for prostate cancer patients.
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Puerarin ameliorates cognitive deficits in streptozotocin-induced diabetic rats
Abstract
Previous research has indicated that Diabetes is a high risk of learning and memory deficits. Puerarin, an isoflavonoid extracted from Kudzu roots, has been reported to possess antioxidant, anti-inflammatory, anti-apoptotic and anti-diabetic properties which are useful in the treatment of various diseases. Recently, Puerarin was found to have the effects on learning and memory performances in humans and animal models. However, up to now, there is no detailed evidence on the effect of Puerarin on diabetes-associated cognitive decline (DACD). In this study, we designed to assess the effects of Puerarin on diabetes-associated cognitive decline (DACD) using a streptozotocin (STZ)-injected rat model and exploring its potential mechanism. Diabetic rats were treated with Puerarin (100 mg/kg per d) for 7 days. The learning and memory function was evaluated by morris water maze test. The acetylcholinesterase (AChE), choline acetylase (ChAT), oxidative indicators [malondialdehyde (MDA) and superoxide dismutase (SOD)] and inflammatory cytokine (TNF-a, IL-1β and IL-6) were measured in hippocampus by using corresponding commercial kits. mRNA and Protein levels of Bcl-2 were analyzed by RT-PCR and Westernblot. The results showed that supplementation of Puerarin improved the learning and memory performances compared with the STZ group by the morris water maze test. In addition, Puerarin supplement significantly prevented AChE and MDA activities, increased ChAT and SOD activities, and alleviated the protein level of TNF-α, IL-1β and IL-6 in the hippocampus compared with the STZ group. Moreover, the pretreatment with Puerarin also significantly increased the Bcl-2 expression. It is concluded that Puerarin possesses neuroprotection to ameliorate cognitive deficits in streptozotocin-induced diabetic rats by anti-inflammatory, antioxidant and antiapototic effects.
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Expanding the phenotype in aminoacylase 1 (ACY1) deficiency: characterization of the molecular defect in a 63-year-old woman with generalized dystonia
Abstract
Aminoacylase 1 (ACY1) deficiency is an organic aciduria due to mutations in the ACY1 gene. It is considered much underdiagnosed. Most individuals known to be affected by ACY1 deficiency have presented with neurologic symptoms. We report here a cognitively normal 63-year-old woman who around the age of 12 years had developed dystonic symptoms that gradually evolved into generalized dystonia. Extensive investigations, including metabolic diagnostics and diagnostic exome sequencing, were performed to elucidate the cause of dystonia. Findings were only compatible with a diagnosis of ACY1 deficiency: the urinary metabolite pattern with N-acetylated amino acids was characteristic, there was decreased ACY1 activity in immortalized lymphocytes, and two compound heterozygous ACY1 mutations were detected, one well-characterized c.1057C>T (p.Arg353Cys) and the other novel c.325A>G (p.Arg109Gly). Expression analysis in HEK293 cells revealed high residual activity of the enzyme with the latter mutation. However, following co-transfection of cells with stable expression of the c.1057C>T variant with either wild-type ACY1 or the c.325A>G mutant, only the wild-type enhanced ACY1 activity and ACY1 presence in the Western blot, suggesting an inhibiting interference between the two variants. Our report extends the clinical spectrum of ACY1 deficiency to include dystonia and indicates that screening for organic acidurias deserves consideration in patients with unexplained generalized dystonia.
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A randomized phase II study of radiation induced immune boost in operable non-small cell lung cancer (RadImmune trial)
Abstract
Background
Lung cancer is the leading cause of cancer deaths worldwide. Surgery, radiotherapy at conventional and high dose and chemotherapy are the mainstay for lung cancer treatment. Insufficient migration and activation of tumour specific effector T cells seem to be important reasons for inadequate host anti-tumour immune response. Ionizing radiation can induce a variety of immune responses. The goal of this randomized trial is to assess if a preoperative single fraction low dose radiation is able to improve anti-tumour immune response in operable early stage lung cancer.
Methods/Design
This trial has been designed as an investigator-initiated, prospective, randomized, 2-armed phase II trial. Patients who are candidates for elective resection of early stage non-small cell lung cancer will be randomized into 2 arms. A total of 36 patients will be enrolled. The patients receive either 2 Gy or no radiation prescribed to their primary tumour. Radiation will be delivered by external beam radiotherapy using 3D radiotherapy or intensity-modulated radiation technique (IMRT) 7 days prior to surgical resection. The primary objective is to compare CD8+ T cell counts detected by immunohistochemistry in resected tumours following preoperative radiotherapy versus no radiotherapy. Secondary objectives include the association between CD8+ T cell counts and progression free survival, the correlation of CD8+ T cell counts quantified by immunohistochemistry and flow cytometry, local tumour control and recurrence patterns, survival, radiogenic treatment toxicity and postoperative morbidity and mortality. Further, frequencies of tumour reactive T cells in blood and bone marrow as well as whole blood cell transcriptomics and plasma-proteomics will be correlated with clinical outcome.
Discussion
This unique intervention combining preoperative low dose radiation and surgical removal of early stage non-small cell lung cancer is designed to address the problem of inadequate host anti-tumour immune response. If successful, this study may affect the role of radiotherapy in lung cancer treatment.
Trial registration
NCT02319408; Registration: December 29, 2014.
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The role of Napsin-A and Desmocollin-3 in classifying poorly differentiating non-small cell lung carcinoma
Publication date: Available online 19 December 2015
Source:Journal of the Egyptian National Cancer Institute
Author(s): Noha El-Sayed Ezzat, Neveen Tahoun
There is increased need for classification of non-small cell lung cancer (NSCLC) into its major subtypes, adenocarcinoma (AC) and squamous cell carcinoma (SCC). Such a classification is enabled in poorly differentiated tumours based on routine morphology due to overlapping morphologic features. In such cases, the use of immunohistochemistry (IHC) can differentiate between the two subtypes.PurposeTo test the ability of the two markers; Napsin-A and Desmocollin-3, in differentiating poorly differentiated (AC) from poorly differentiated SCC in small biopsies.Patients and methodsThis is a retrospective study including 60 patients who presented with pulmonary nodules. Cases with biopsy specimens diagnosed as poorly differentiated non-small cell lung cancer, and had corresponding resection specimens were included. Cell blocks were stained with anti Napsin-A, and anti Desmocollin-3. Cytoplasmic immunoreactivity for both markers was considered specific. Sensitivity, specificity, positive and negative predictive values, total accuracy and combined accuracy of both markers were calculated.ResultsNapsin A showed a sensitivity of 89.3%, a specificity of 96.9%, PPV of 96.2%, NPV of 91.2%, and a total accuracy of 93.3% for AC, while Desmocollin-3 achieved 90.6% sensitivity, 96.4% specificity, 96.7% PPV, 90% NPV, and 93.3% total accuracy. Both markers achieved a total accuracy of 90%.ConclusionNapsin-A, and Desmocollin-3 were sensitive and specific markers for the diagnosis of AC and SCC, respectively. Both markers allowed classification of 54/60 cases into either AC or SCC.
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[Pathological complete response: A predictive survival factor after neoadjuvant chemotherapy in lung cancer].
[Pathological complete response: A predictive survival factor after neoadjuvant chemotherapy in lung cancer].
Bull Cancer. 2015 Dec 9;
Authors: Milleron B, Westeel V, Gounant V, Wislez M, Quoix E
Abstract
The phase III trials of adjuvant and neoadjuvant chemotherapy showed a 5 % increase survival but the clinical research in this area is difficult because the duration of the trials with overall survival as primary end point is around 10years. To shorten the duration of these studies, the use of surrogate end points such as disease-free survival or relapse-free survival is possible, but does not significantly reduce the duration of studies. Several studies in and outside the lung cancer showed histological complete response or the percentage of viable tumor cells after chemotherapy could be correlated with survival and thus become an interesting alternative criterion. If this is verified, clinical studies of preoperative chemotherapy should be shortened which would allow patients faster access to innovative treatment in the perioperative situation.
PMID: 26682626 [PubMed - as supplied by publisher]
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Clinical updates in adult acute lymphoblastic leukemia
Publication date: Available online 19 December 2015
Source:Critical Reviews in Oncology/Hematology
Author(s): Omar Al Ustwani, Neha Gupta, Hatoon Bakhribah, Elizabeth Griffiths, Eunice Wang, Meir Wetzler
Acute lymphoblastic leukemia (ALL) is a clonal disease characterized by B or T lineage. Here we cover the clinical manifestations, pathophysiology and therapy for ALL. Additionally, we will discuss the evidence for minimal residual disease assessment, novel molecular targets and newly developed targeted therapies. The separation of ALL into Philadelphia chromosome positive and recently into Philadelphia-like disease represents the most exciting developments in this disease. Finally, the advent of new immunotherapeutic approaches led us to predict that in few years, ALL therapy might be based heavily on non-chemotherapeutic approaches.
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EGFR monoclonal antibodies in locally advanced head and neck squamous cell carcinoma: What is their current role?
Publication date: Available online 19 December 2015
Source:Critical Reviews in Oncology/Hematology
Author(s): Mohamed Alorabi, Nicole A Shonka, Apar Kishor Ganti
Treatment options for locally advanced squamous cell carcinoma of the head and neck (SCCHN) include either surgical resection followed by radiation or chemoradiation, or definitive chemoradiation for which single-agent cisplatin is the best studied and established. The increasing understanding of the molecular biology of SCCHN has led to an interest in the development of targeted therapies. The epidermal growth factor receptor (EGFR) is over-expressed in nearly 80-90% of cases of SCCHN and correlates with poor prognosis and resistance to radiation. Preclinical evidence showed that blocking EGFR restores radiation sensitivity and enhances cytotoxicity. This finding led to clinical trials evaluating this class of agents and the approval of cetuximab in combination with radiation for the treatment of locally advanced SCCHN. This review is focused on the anti-EGFR monoclonal antibodies and their role either with radiotherapy or chemoradiation in unresectable LA SCCHN.
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