Patients with chronic myeloid leukaemia show an excellent response to treatment with imatinib. However, in some patients, the disease is resistant to imatinib. This resistance may be related to the presence of genetic variations on the drug's pharmacokinetics and metabolism. We therefore studied three polymorphisms (C1236T, G2677T and C3435T) in the human multidrug-resistance gene (MDR1) in 86 patients with chronic myeloid leukaemia treated with imatinib. Imatinib resistance was more frequent in patients with TT genotype at locus 1236 than in those with CT/CC genotypes (p=0.003). For the other two loci (G2677T and C3435T), resistance was seen to be higher for TT genotype when compared to GG/GT and CT/CC but it was not statistically significant (p=0.13 and p=0.099). In conclusion, determination of C1236T MDR1 genotype may help to predict response to imatinib therapy in patients with chronic myeloid leukaemia.

The purpose of this study is to evaluate the association between intron 1 CA-repeat polymorphisms of the epidermal growth factor receptor gene (EGFR) and the clinical outcome of Chinese patients with advanced non-small cell lung cancer (NSCLC) treated with EGFR tyrosine kinase inhibitors (TKIs). We genotyped the intron 1 CA-repeat genetic polymorphisms of EGFR in 84 Chinese patients with NSCLC. The relationship between the length of the CA repeats and EGFR mutations in exons 18-21 in the 84 patients was elucidated. We then analyzed the association between the length of the CA repeats and the clinical outcome of EGFR-TKI-treated patients with NSCLC. EGFR mutations in exon 19 were significantly associated with shorter CA repeats. Patients with shorter CA repeats had a significantly longer progression-free survival with EGFR-TKI treatment than those with longer CA repeats. Our results suggest that shorter CA repeats in intron 1 of EGFR are associated with EGFR mutations and the clinical outcomes of TKI-treated patients with NSCLC.

There is only limited data on the prevalence of epidermal growth factor receptor (EGFR) activating mutations in squamous cell carcinomas and adenosquamous carcinomas of the lung in patients of the Southern Bulgarian region and the efficacy of EGFR tyrosine kinase inhibitors.

Non-small-cell lung cancer (NSCLC) is the most common non-acquired immune deficiency syndrome-related malignancy responsible for death. Mutational status is crucial for choosing treatment of advanced NSCLC, yet no data is available on the frequency of epidermal growth factor receptor (EGFR) and Kirsten ras (KRAS) mutations and their impact on NSCLC in human immunodeficiency virus (HIV)-infected patients (HIV-NSCLC). All consecutive HIV-NSCLC patients diagnosed between June 1996 and August 2013 at two Paris university hospitals were reviewed, with tumor samples analyzed for EGFR and KRAS mutational status. Overall, 63 tumor samples were analyzed out of 73 HIV-NSCLC cases, with 63% of advanced NSCLC. There were 60 non-squamous and nine squamous cell carcinomas, with EGFR and KRAS mutations identified in two (3.3%) and seven (11.5%) tumors, respectively. The proportion of KRAS mutations was 29% if solely the more sensitive molecular techniques were considered. The two patients with advanced adenocarcinoma harboring EGFR mutations exhibited lasting partial response to EGFR-tyrosine kinase inhibitors. Overall survival for patients with advanced NSCLC were >30 months for those with EGFR mutations, <3 months for KRAS mutations (n=2), and the median was 9 months [4.1-14.3] for wild-type (n=34). In multivariate analysis, KRAS mutation and CD4<200 cells/μL were associated with poor prognosis (hazard ratio (HR): 24 [4.1-140.2], p=0.0004; HR: 3.1 [1.3-7.5], p=0.01, respectively). EGFR mutation must be investigated in HIV-NSCLC cases due to its predictive and prognostic impact, whereas KRAS mutation is of poor prognostic value. Clinicians should search for drugs dedicated to this target population.

Pioneer transcription factors constitute a heterogeneous group of regulatory proteins of animals, which, unlike other transcription factors, are able to recognize and bind target DNA sequences within closed chromatin. This binding can change the local chromatin structure and facilitate binding of other proteins, thus establishing competence for gene expression. The ability to bind silent genes in the closed environment makes the pioneer factors very useful in the processes leading to cardinal alteration of cell phenotype, such as differentiation in embryonic development or cell reprogramming. These proteins can remain bound to target sequences during mitotic division, and due to this probably take part in the maintenance of cellular memory. Apparently, pioneer transcription factors are active participants in carcinogenesis and maintenance of tumor cell phenotype, although their role in these processes needs additional research. It is reasonable to suppose that a further study will help to shed more light on the genetic processes in embryonic development, increase the efficiency of cell reprogramming and also develop new approaches to diagnostics and therapy of cancer diseases.

To study the prevalence of BRAF(V600E) mutations in small (≤ 2 cm) papillary thyroid carcinoma (PTC), explore the correlation with occult central nodal metastasis (CNM) of clinically-nodal negative (cN0) neck for small (≤ 2 cm) papillary thyroid carcinoma (PTC).

The Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Nazionale Tumori "Fondazione G. Pascale" (INT-Pascale) is the largest Clinical Care and Research Cancer Center in Southern Italy. The mission is prevention, diagnosis, and care of cancer and innovative research in oncology. In 2013, INT-Pascale joined the Organisation of European Cancer Institutes (OECI) accreditation and classification project along with other Italian IRCCS cancer centers. One of the major OECI requirements that a cancer center must fulfill in order to achieve and maintain OECI certification is a strong emphasis in translational and clinical research: increasing the number of patients enrolled in clinical trials, establishing easily accessible databases for operators, and informing all possible stakeholders, including patients. A characterizing theme of INT-Pascale is a strong commitment to clinical experimental studies. In the 2007-2014 period, 440 clinical trials were activated at INT-Pascale; in this period, the number of clinical trials and observational studies has had an increment achieving in 2014, respectively, the share of 60 clinical trials and 35 observational studies activated. Optimization of clinical trials management and dissemination of the clinical research culture at INT-Pascale are main objectives to be achieved through several actions and procedures being implemented as a component of the OECI improvement plan. Participation in the OECI program has represented an important challenge to improve quality and processes related to promoting, prioritizing, and monitoring clinical trials at INT-Pascale.

Adiponectin is an adipocyte-specific adipocytokine with proliferative and pro-angiogenic effects that regulates many biological processes, including immunity, insulin resistance, and inflammation. The oncogenic role of adiponectin has been implicated in several cancer types. Stromal cells within tumor contribute tumor growth and angiogenesis; however, it is not clear that how adiponectin regulates stromal cell-mediated tumorigenesis. In this study, using the tumor xenograft models, we demonstrated that tumor development was severely impaired in mouse subcutaneous cancer tissue and metastasis tumor tissue in adiponectin knockout mice. Our results indicated adiponectin deficiency resulted in decrease of blood vessel and stromal senescent fibroblasts in subcutaneous and metastasis tumor tissue. These observations were confirmed in vitro, in which co-cultured tumor cells and fibroblasts treated with adiponectin promoted ECs tube formation. A secretion of CXCL1 by adiponectin-treated tumor cells was observed during the process of inducing stromal fibroblast senescence. Furthermore, stromal cells senescence was through p53 and p16 pathways. Taken together, our results indicate that adiponectin promotes stromal cell senescence within invasive colon cancer contributing to angiogenesis and tumor growth in part through the production of CXCL1 and may serve as a therapeutic target for tumor patients. © 2015 Wiley Periodicals, Inc.

Local ablative therapy with stereotactic ablative radiotherapy may improve survival in oncogene-addicted lung cancer patients with extracranial oligometastatic disease treated with targeted therapies. There is limited data on the use of radiofrequency ablation (RFA) in this same setting. We present a case of an anaplastic lymphoma kinase (ALK)-positive lung cancer patient with hepatic oligometastatic progression who was successfully treated with both stereotactic ablative radiation and RFA while continuing with an ALK inhibitor.

Mutations in the p53 tumor suppressor gene are one among the most common genetic abnormalities to be described in breast cancer. However, there are a few recant reports on non-viral vector-mediated p53 gene delivery in breast cancer.

High mortality from breast cancer is associated with the high heterogeneity of tumor and the frequent recurrences of the pathological process, which are due to the presence of tumor stem cells. The review considers the biological properties of tumor stem cells, the molecular mechanisms of their regulation, interaction with the microenvironment, and their role in the heterogeneity of the morphological and clinical forms of breast cancer.

The peripheral T-cell lymphomas (PTCLs) account for 5% to 10% of all non-Hodgkin lymphomas. In the up-front setting, approximately one-quarter of patients experience a long-term remission. In the setting of relapsed and refractory disease, the median progression-free survival and overall survival are reported to be only 3.7 and 6.5 months, respectively. Unfortunately, the molecular and genetic characterization of PTCL has lagged well behind that of the B-cell lymphomas, although several recent experiences are shedding light on the remarkable molecular heterogeneity that has come to define these diverse diseases. The need to identify new active drugs for patients with PTCL has been addressed in part over the last several years, as 4 drugs have now been approved by the US Food and Drug Administration for patients with relapsed or refractory disease, and a plethora of new studies exploring novel combinations have begun to emerge. More advanced techniques in molecular biology, such as next-generation sequencing, gene expression profiling, and comparative genomic hybridization, have helped identify subtleties among subtypes and potentially identify new targets. Many of these recent clinical advances have been based on the recognition that PTCL is a disease that may be broadly characterized by gross epigenetic dysregulation with sensitivity to histone deacetylase inhibitors. In this report, we discuss emerging new therapies in relapsed and refractory PTCL and try to place these new findings in the evolving biological understanding of the disease.

Advances in genomic sequencing and insights into molecular leukemogenesis are opening the door to using targeted agents to tailor treatment for acute myeloid leukemia (AML) in individual patients. Although this shift away from traditional cytotoxic therapies represents an innovative approach to AML therapy, a number of obstacles stand in the way of widespread adoption of targeted therapy into daily practice. For example, the effects of single agents are marginal, and the degree of variability among patients is great. Some have advocated incorporation of newly identified biomarkers into clinical trials to guide patient-specific treatment, but the relevance of these biomarkers to clinical response is uncertain and requires further validation. Combining targeted agents with other targeted agents or with conventional chemotherapy to overcome the biological heterogeneity of AML may enhance treatment efficacy; however, drug toxicities also are increased and drug resistance continues to occur. Overall survival is an impractical endpoint for clinical trials of AML, which may be addressed by using the endpoint of event-free survival to evaluate novel targeted agents. Another barrier to implementation is the high cost and limited availability of targeted agents. Herein, we address the above practical questions and propose potential strategies for the future evaluation of targeted treatments.

Approximately 5-10% of breast cancer cases appear in families at a higher rate and at an earlier onset than in the average population. Two known gene defects, BRCA1 and BRCA2, account for the majority of these hereditary related breast cancers. Additionally, BRCA1 and BRCA2 are related to the Hereditary Breast and Ovarian Cancer syndrome (HBOC), where risk for other related cancers are increased. Various health-care professional organizations provide guidelines that speak to the need for conducting risk assessments, but little research has been conducted focusing on the initial screening for this syndrome. This quality improvement project attempts to determine if Nurse Navigators can effectively perform the initial education and screening for HBOC syndrome within a mammography and women's breast imaging setting using a simplified patient history tool. E. M. Rodgers' Diffusion of Innovation model, a map of how new ideas and programs have become adopted and accepted, guided this project's development and implementation. Over the course of 8 weeks, 1,420 women seeking service at 3 mammography and imaging sites were given a new risk assessment tool for HBOC. Additionally, the use of Nurse Navigation to identify women who may be at risk for HBOC was implemented. Two populations seeking service at the study sites were evaluated: (1) women obtaining breast screening/imaging services and (2) women receiving breast biopsy results. Patients identified as "at-risk" were defined by evidence-based practice guidelines from the National Comprehensive Cancer Network and were referred for further genetic evaluation by a genetic professional. During this initial implementation of the HBOC risk assessment program, low participation of screening/imaging patients requesting HBOC education and evaluation occurred (129 screening patients or 9%). High rates of positive biopsy patients (5 patients or 34.7%) werefound to be at risk for HBOC compared to similar studies. Identifying HBOC risk at the time of breast biopsy results gave the opportunity to impact the timing and kind of surgical management of patients at risk for this syndrome.The Commission on Cancer (CoC), an arm of the American College of Surgeons, provides practice guideline standards and accreditation for cancer programs. Patients will become more familiar with being assessed for HBOC and other hereditary cancers during their annual health-care visits and more identification of patients at riskfor HBOC should occur as new CoC 2012 standards requiring hereditary cancer risk assessments for a cancer program's certification are enacted.