International Journal of Cancer. Journal International du Cancer

Oncogenic KRAS is considered a promising target for anti-cancer therapy. However, direct pharmacological strategies targeting KRAS-driven cancers remained unavailable. The prenyl-binding protein PDEδ, a transporter of KRAS, has been identified as a potential target for pharmacological inhibitor by selectively binding to its prenyl-binding pocket, impairing oncogenic KRAS signaling pathway. Here, we discovered a novel PDEδ inhibitor (E)-N'-((3-(tert-butyl)-2-hydroxy-6,7,8,9-tetrahydrodibenzo[b,dfuran-1-yl)methylene)-2,4-dihydroxybenzohydrazide(NHTD) by using a high-throughput docking-based virtual screening approach...

Human papillomavirus 8 (HPV8) is associated with the development of squamous cell carcinomas (SCC) of the skin. HPV-infected keratinocytes are able to over-ride normal checkpoint control mechanisms and sustain cell cycle activity, allowing for synthesis of cellular proteins necessary for viral genome amplification. To study how HPV8 may disrupt cell-cycle control, we analysed the impact of HPV8 early gene expression on one of the key regulators of cell cycle and DNA damage response, checkpoint kinase-1 (CHK1)...

Tumor angiogenesis is critical for tumor progression as the new blood vessels supply nutrients and facilitate metastasis. Previous studies indicate tumor associated lymphocytes, including B cells and T cells, contribute to tumor angiogenesis and tumor progression. The present study aims to identify the function of Lymphotoxin-α (LT-α), which is secreted by the activated lymphocytes, in the tumor angiogenesis of head and neck squamous cell carcinoma (HNSCC). The co-culture system between HNSCC cell line Cal27 and primary lymphocytes revealed that tumor cells promoted the LT-α secretion in the co-cultured lymphocytes...

Impaired metabolism may play an important role in the pathogenesis of lethal prostate cancer, yet there is a paucity of evidence regarding the association. We conducted a large prospective serum metabolomic analysis of lethal prostate cancer in 523 cases and 523 matched controls nested within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study. Median time from baseline fasting serum collection to prostate cancer death was 18 years (maximum 30 years). We identified 860 known biochemicals through an ultrahigh-performance LC-MS/MS platform...

Whereas cancer patients have benefited from liquid biopsies, the scenario for gastric adenocarcinoma (GAC) is still dismal. We used next-generation deep sequencing of TP53 - a highly mutated and informative gene in GAC - to assess mutations in tumor biopsies, plasma (PL) and stomach fluids (gastric wash - GW). We evaluated their potential to reveal tumor-derived mutations, useful for monitoring mutational dynamics at diagnosis, progression, and treatment. Exon-capture libraries were constructed from 46 patients including tumor biopsies, GW and PL pre and post-treatment (196 samples), with high vertical coverage >8,000X...

Soft tissue sarcomas (STS) are rare tumors of mesenchymal origin. About 50% of patients with STS experience relapse and more than 30% will die within 10 years after diagnosis. In this study we investigated circulating free DNA (cfDNA) and tumor-specific genetic alterations therein (circulating tumor DNA, ctDNA) as diagnostic biomarkers. Plasma concentrations and fragmentation of cfDNA was analyzed with quantitative PCR. Patients with STS (n=64) had significantly higher plasma concentrations and increased fragmentation of cfDNA when compared to patients in complete remission (n=19) and healthy controls (n=41) (p<0...

Limited studies investigated clinicopathological and prognostic significance of histologic and molecular subgroups of gastric cancer concurrently. We retrospectively enrolled 1,248 patients with gastric cancer who received radical gastrectomy with lymphadenectomy and classified these cases into the Epstein-Barr virus (EBV)-associated and microsatellite instability (MSI)-associated subtypes by EBV-encoded small RNA in situ hybridization and immunohistochemical stains for DNA mismatch repair proteins, respectively...

Our aim was to estimate how long-term mortality following breast cancer diagnosis depends on age at diagnosis, tumor estrogen receptor (ER) status, and the time already survived. We used the population-based Australian Breast Cancer Family Study which followed-up 1,196 women enrolled during 1992-99 when aged <60 years at diagnosis with a first primary invasive breast cancer, over-sampled for younger ages at diagnosis, for whom tumor pathology features and ER status were measured. There were 375 deaths (median follow-up=15...

No abstract text is available yet for this article.

This systematic review, stimulated by inconsistency in secondary evidence, reports the benefits and harms of breast cancer (BC) screening and their determinants according to systematic reviews. A systematic search, which identified 9,976 abstracts, led to the inclusion of 58 reviews. BC mortality reduction with screening mammography was 15-25% in trials and 28-56% in observational studies in all age groups, and the risk of stage III+ cancers was reduced for women older than 49 years. Overdiagnosis due to mammography was 1-60% in trials and 1-12% in studies with a low risk of bias, and cumulative false-positive rates were lower with biennial than annual screening (3-17% vs 0...

High mammographic density is a well-known risk factor for breast cancer. This study aimed to search for a possible birth cohort effect on mammographic density, which might contribute to explain the increasing breast cancer incidence. We separately analysed left and right breast density of Dutch women from a 13-year period (2003-2016) in the breast cancer screening programme. First, we analysed age-specific changes in average percent dense volume (PDV) across birth cohorts. A linear regression analysis (PDV vs...

The androgen receptor (AR) has potential clinical relevance in metastatic breast cancer (mBC) since it might be a treatment target and has been associated with endocrine resistance. A minimal-invasive way to determine AR expression on metastatic tumor cells is by characterization of circulating tumor cells (CTCs). Here, we assessed AR mRNA expression in CTCs (CTC-AR) and in matched primary tumor samples from mBC patients representing different breast cancer subtypes. In addition, we explored CTC-AR-status in relation to outcome on endocrine therapy...

The P2X7 receptor, an ATP-gated ion channel, is critical for cancer cell growth, invasiveness, and angiogenesis. Previous studies indicate that P2X7 regulates osteoblast proliferation and osteodeposition and that high P2X7 expression has a pro-growth effect in osteosarcoma. However, how it functions in osteosarcoma cell growth and metastasis is not clear. Thus, we elucidated molecular mechanisms of P2X7-dependent positive regulation of osteosarcoma cell proliferation, invasion, migration, epithelial to mesenchymal transition (EMT), and angiogenesis using in vitro and in vivo models...

No abstract text is available yet for this article.

The International Agency for Research on Cancer first concluded that alcohol causes cancer in humans in 1988. The World Cancer Research Fund has declared that alcohol causes cancer of the oral cavity, pharynx, larynx, oesophagus (squamous cell carcinoma), female breast, colon, rectum, stomach and liver. It recommended that alcohol be avoided altogether to prevent cancer. We aimed to quantify the impact of reducing alcohol consumption on future cancer incidence in Australia. We used PREVENT 3.01 simulation modelling software to estimate the proportion of cancers that could potentially be prevented over a 25-year period under two hypothetical intervention scenarios and two latency periods (20 and 30 years)...

The phase III DATA study investigates the efficacy of adjuvant anastrozole (6 versus 3 year) in postmenopausal women with breast cancer previously treated with 2-3 years of tamoxifen. This planned side-study assessed patterns of care regarding detection and treatment of osteopenia/osteoporosis, and trends in bone mineral density (BMD) during and after therapy. We registered all BMD measurements and bisphosphonate-use. Time to osteopenia/osteoporosis was analysed by Kaplan Meier methodology. For the trend in T-scores we used linear mixed models with random patients effects...

Cell free DNA (cfDNA) in human plasma carries abundant information, which has therefore been the key sample for non-invasive prenatal testing (NIPT) and liquid biopsy. Especially by using the rapidly developed next-generation sequencing (NGS) techniques, the genetic and epigenetic information embedded in cfDNA has been effectively and extensively decoded. In this process, a key step is to construct the NGS library. Due to its high degradation, the single strand-based method was reported to be more qualified to construct the NGS library of cfDNA...

The aetiology of childhood acute lymphoblastic leukaemia (ALL) is unclear. Genetic abnormalities have been identified in a number of ALL cases, although these alone are not sufficient for leukaemic transformation. Various in utero and post-natal environmental exposures have been suggested to alter risk of childhood ALL. DNA methylation patterns can be influenced by environmental exposures, and are reported to be altered in ALL, suggesting a potential mediating mechanism between environment and ALL disease risk...

Despite encouraging results with chimeric antigen receptor T (CART) cells, outcome can still be improved by optimization of the CART cell generation process. The proportion of less-differentiated T cells within the transfused product is linked to enhanced in vivo CART cell expansion and long-term persistence. The clinically approved PI3Kδ inhibitor idelalisib is well established in the treatment of B cell malignancies. Besides B cell receptor pathway inhibition, idelalisib can modulate T cell differentiation and function...

Benzene is considered a carcinogen, mostly based on evidence of causality for myeloid leukemia from high levels of exposure in occupational studies. We used U.S. Environmental Protection Agency National Ambient Toxics Assessment (NATA) estimates of low-level ambient benzene to examine potential associations for the general public between benzene exposure and risk of hematologic cancers. Exposure was estimated by linking participants' residential address to the NATA benzene estimates for that census tract. Among 115,996 American Cancer Society Cancer Prevention Study-II Nutrition cohort participants (52,554 men, 63,442 women), 2,595 were diagnosed with incident hematologic cancer between 1997 and 2013...