Cancer

The potential role of cyanide-bridged platinum-iron complexes as novel anti-cancer Pt(IV) prodrug is studied.  We present design  principles of a dual-functional prodrug that can release up to six  cisplatin agents per prodrug unit concurrently with a ferricyanide. The functionality of the prodrug is addressed through density functional theory (DFT) calculations. The predicted effective prodrug molecule is a unique hepta-metal center complex consisting of a ferricyanide core with the six cyano ligands each bridging through  ligand bond a Pt(IV) center...

Nivolumab can cause interstitial lung disease (ILD), which may be fatal; however, mortality risk factors have not been identified. This post-marketing study evaluated the poor prognostic factors of ILD in nivolumab-treated patients with non-small cell lung cancer (NSCLC) in Japan. Clinical and chest imaging findings for each ILD case were assessed by an Expert Central Review Committee, and prognosis was evaluated by radiographic findings, including the presence/absence of peritumoral ground glass opacity (peritumoral-GGO)...

AIMS: Ningetinib is a tyrosine kinase inhibitor for the treatment of non-small cell lung cancer (NSCLC). The present study aims to investigate the drug interaction of ningetinib and gefitinib and the mechanism of high plasma exposure of N-demethylated ningetinib (M1) in NSCLC patients. METHODS: Patients with NSCLC were recruited. Metabolism and transport assays were performed using in vitro models. Deuterated M1 was used to study the effects of ningetinib and gefitinib on M1 efflux in ICR mice...

INTRODUCTION AND AIM: RNF43 is suggested to be involved in the serrated pathway towards colorectal cancer and encodes a transmembrane Ring-type E3 ubiquitin ligase that negatively regulates the Wnt pathway. This study aims to elucidate the role of RNF43 gene variants in serrated polyposis syndrome (SPS) and serrated polyps. METHODS: Three cohorts were tested. The first cohort included germline DNA of 26 SPS patients tested for pathogenic variants in RNF43 by Sanger sequencing all exons...

Immune checkpoint blockade (ICB) has revolutionized cancer therapy, but varying response rates illustrate the need for biomarkers of response. Studies in mice have identified a subset of CD8 T cells that is essential for response to PD-1 ICB. These CD8 T cells co-express CXCR5, PD-1 and Tcf1, and provide effector T cells upon PD-1 ICB. It is unknown whether similar T cells play a role in PD-1 ICB in humans. We studied human peripheral blood (PB) and lymph nodes (LN) for the frequency, phenotype and functionality of CXCR5+ PD-1+ CD8 T cells...

Upregulation of the forkhead box protein Q1 ( FOXQ1 ) promotes bladder cancer (BCa) cell growth and metastasis. Factors affecting FOXQ1 expression at the post-transcriptional level have not yet been identified. We performed cell proliferation, cell invasion, and tumorigenesis experiments to characterize the relationship between FOXQ1 and miR-140-3p . We found that FOXQ1 was significantly upregulated and miR-140-3p was significantly downregulated in BCa tissues. We also identified an inverse correlation between miR-140-3p and FOXQ1 expression in BCa tissues...

Hormone receptor-positive breast cancer accounts for around 75% of breast cancers. The estrogen receptor pathway promotes tumor progression and endocrine resistance. Recently, the cross-talk between the ER signaling pathway and cell cycle regulation has been identified. It is necessary to determine the underlying molecular mechanisms involved in the ER signaling pathway and find new target genes for prognosis and drug resistance in ER+ breast cancer. In this study, lncRNA MAFG-AS1 was shown to be up-regulated and associated with poor prognosis in ER+ breast cancer...

Dendritic cells (DCs) play a crucial role in the complex interplay between tumor cells and the immune system. During the elimination phase of cancer immunoediting, immunostimulatory DCs are critical for the control of tumor growth. During the escape phase, regulatory DCs sustain tumor tolerance and contribute to the development of the immunosuppressive tumor microenvironment that characterizes this phase. Moreover, increasing evidence indicates that DCs are also critical for the success of cancer immunotherapy...

Poly (ADP-ribose) polymerase (PARP) is a superfamily of 18 proteins characterized by the PARP homology domain, the catalytic domain. This catalytic domain helps in the ADP-ribosylation of various acceptor proteins using nicotinamide adenine dinucleotide (NAD+) as a donor for ADP-ribose. PARP-1 and PARP-2 carry out 80% of poly-ADP-ribosylation of cellular protein. Hence, their combined knockout results in embryonic lethality of mice. PARP-1 consists of three major domains, namely, DNA binding domain, automodification domain, and a catalytic domain...

PURPOSE: Women with a first-degree family history of breast cancer (FHBC) are sometimes advised to initiate screening mammography when they are 10 years younger than the age at which their youngest relative was diagnosed, despite a lack of unambiguous evidence that this is an effective strategy. It is unknown how often this results in women initiating screening earlier (< 40 years) than screening guidelines recommend for average-risk women. METHODS: We examined screening initiation age by FHBC and age at diagnosis of the youngest relative using data collected by the Breast Cancer Surveillance Consortium on 74,838 first screening mammograms performed between 1996 and 2016...

Prognosis for some histological variants of a rare breast disease, phyllodes tumors, is evaluated. The prognostic potential of some molecular biological factors significantly correlating with breast cancer prognosis is evaluated on a unique clinical material (244 cases with benign, intermediate, and malignant phyllodes tumors). The development of benign phyllodes tumor relapse directly correlated with the number of G0/1-phase cells and inversely correlated with the number of cells in the G2+M and S phases. The level of steroid hormone receptors in phyllodes tumors cannot serve as a prognostic marker predicting the disease course...

A comprehensive radio-ecological evaluation of soil samples of Solan and Shimla districts of Himachal Pradesh has been carried out for risk and dose assessment. Twenty-six randomly selected environmental soil samples were analysed for natural radionuclide concentrations (226 Ra, 232 Th and 40 K) using NaI(Tl) scintillator detector. The average concentration of 226 Ra, 232 Th and 40 K was observed as 37, 59 and 430 Bq kg-1 , respectively, which exceeded the worldwide average of 33, 45 and 412 Bq kg-1 reported by UNSCEAR (Sources and effects of ionizing radiation...

PURPOSE: Health state utility values are commonly used to inform economic evaluations and determine the cost-effectiveness of an intervention. The aim of this systematic review is to summarise the utility values available to represent the health-related quality of life (HRQoL) of patients with thyroid cancer. METHODS: Eight electronic databases were searched from January 1999 to April 2019 for studies which included assessment of HRQoL for patients with thyroid cancer...

The combined positive score (CPS) and tumor proportion score (TPS) have been developed to evaluate programmed death ligand-1 (PD-L1) expression, especially due to the potential benefit of the targeted therapy. However, the prognostic value of PD-L1 scoring systems in gastric cancer (GC) remains unclear. This study aimed to evaluate PD-L1 expression according to CPS and TPS in curative resected GC patients and its correlation with prognosis. We retrospectively evaluated 284 GC patients who underwent D2-gastrectomy by tissue microarray...

Stemness phenotype is considered as the centerpiece of cancer biology due to its potential in conventional chemo-radiotherapy resistance and tumor recurrence after clinical intervention. This feature in tumor mass belongs to activation of core regulatory stemness factors and different cell signaling pathways in cancer stem cells. We aimed in this study to elucidate contribution of Notch signaling pathway in stemness state of esophageal squamous cell carcinoma (ESCC) through their relevance with stem cell markers SOX2 and SALL4...

PURPOSE: We conducted a phase 1 study to determine the maximum tolerated dose and the recommended dose of gemcitabine/nab-paclitaxel/S-1 combination chemotherapy in patients with unresectable pancreatic cancer. METHODS: We enrolled patients aged 20 years or older with unresectable pancreatic cancer and who had not been treated with chemotherapy or radiation therapy. Gemcitabine and nab-paclitaxel were administered on days 1 and 8, and S-1 was administered orally twice daily for 2 weeks, repeated every 3 weeks...

PURPOSE: The Hippo pathway has broadened in cancer research in the past decade and revealed itself to be an important driver for tumorigenesis and metastatic spread. In this study, we investigated the clinical relevance of the Hippo pathway with regard to metastatic invasion, patients' outcome and histopathological features. METHODS: Protein expression of components of the Hippo pathway were analyzed by immunohistochemistry (IHC) using paraffin-embedded tissue from 103 patients who had been diagnosed with pancreatic ductal adenocarcinoma and had undergone surgery...

Although most gastrointestinal tumours are sensitive to 5-fluorouracil (5FU), drug resistance is commonly occurred after 5FU therapy in gastric cancer (GC). Loganetin is the primary active compound in Cornus officinali. However, the synergetic effects of loganetin and 5FU on GC remain unknown. Here, we investigated the synergetic effects and the underlying mechanism of loganetin and 5FU on proliferation, stem-like properties, migration, and invasion of GC both in vitro and in vivo. We found that loganetin alone inhibited the proliferation, stem-like properties, migration and invasion of GC cells in vitro...

PURPOSE: The prognosis for colorectal cancer (CRC) patients is drastically impacted by the presence of lymph node or liver metastases at diagnosis or resection. On this basis we sought to identify novel proteins as biomarkers and determinants of CRC metastasis. EXPERIMENTAL DESIGN: Proteomic analyses were undertaken using primary tissues from ten Chinese CRC patients presenting with or without liver metastases and immunohistochemistry used to validate selected proteins in an independent patient cohort...

The J-CAPRA score is an assessment tool which stratifies risk and predicts outcome of primary androgen deprivation therapy (ADT) using prostate-specific antigen, Gleason score, and clinical TNM staging. Here, we aimed to assess the generalisability of this tool in multi-ethnic Asians. Performance of J-CAPRA was evaluated in 782 Malaysian and 16,946 Japanese patients undergoing ADT from the Malaysian Study Group of Prostate Cancer (M-CaP) and Japan Study Group of Prostate Cancer (J-CaP) databases, respectively...