Cancer

BACKGROUND: To compare the effect of robot-assisted (RAPN) vs. open (OPN) partial nephrectomy on short-term postoperative outcomes and total hospital charges in frail patients with non-metastatic renal cell carcinoma (RCC). METHODS: Within the National Inpatient Sample database we identified 2745 RCC patients treated with either RAPN or OPN between 2008 and 2015, who met the Johns Hopkins Adjusted Clinical Groups frailty-defining indicator criteria. We examined the rates of RAPN vs...

INTRODUCTION: Surveillance care including routine physical exams and testing following gastrointestinal (GI) cancer treatment can be fiscally and emotionally burdensome for patients. Emerging technology platforms may provide a resource-wise surveillance strategy. However, effective implementation of GI cancer surveillance is limited by a lack of patient level perspective regarding surveillance. This study aimed to describe patient attitudes toward GI cancer surveillance and which care modalities such as telemedicine and care team composition best meet the patient's needs for follow-up care...

Discovery of novel anticancer drugs which have low toxicity and high activity is very significant area in anticancer drug research and development. One of the important targets for cancer treatment research is topoisomerase enzymes. In order to make a contribution to this field, we have designed and synthesized some 5(or 6)-nitro-2-(substitutedphenyl)benzoxazole (1a-1r) and 2-(substitutedphenyl)oxazolo[4,5-b]pyridine (2a-2i) derivatives as novel candidate antitumor agents targeting human DNA topoisomerase enzymes (hTopo I and hTopo IIα)...

Development of inhibitors targeting CDK12/13 is of increasing interest as a potential therapy for cancers as these compounds inhibit transcription of DNA damage response (DDR) genes. We previously described THZ531, a covalent inhibitor with selectivity for CDK12/13. In order to elucidate structure-activity relationship (SAR), we have undertaken a medicinal chemistry campaign and established a focused library of THZ531 analogs. Among these analogs, BSJ-01-175 demonstrates exquisite selectivity, potent inhibition of RNA polymerase II phosphorylation, and downregulation of CDK12-targeted genes in cancer cells...

Non-small cell lung cancer (NSCLC) patients with oncogenic ROS1 rearrangements would inevitably develop drug resistance and disease progression after receiving targeted oncogene therapy. Here, we present a metastatic lung adenocarcinoma patient harboring a CD74-ROS1 fusion who initially responded to crizotinib and then developed resistance after acquiring a rarely reported BRAF V600E mutation.

BACKGROUND: Rutaecarpine (Rut) is a plant alkaloid abundant in Euodia ruticarpa which is a Chinese herbal medicine used for treating various cancers. However, the Rut administration effect on prostate cancer in vivo remains unclear. AIM: In the present study we established an allogenic TRAMP-C1 prostate cancer mouse model to evaluate the Rut administration effect and mechanism in vivo. METHODS: To unravel the Rut administration effect on prostate cancer in vivo, C57BL/6J male mice (8 weeks old) were randomly grouped (n = 9), subcutaneously loaded with TRAMP-C1 prostate cancer cells and immediately given daily by gavage with Rut dissolved in soybean oil at 7 mg (low dose), 35 mg (medium dose), and 70 mg/kg b...

Tumor angiogenesis plays a vital role in tumor growth and metastasis. It is proven that in tumor vasculature, endothelial cells (ECs) originate from a small population of cancer cells introduced as cancer stem cells (CSCs). Autophagy has a vital role in ECs differentiation from CSCs and tumor angiogenesis. High levels of reactive oxygen species (ROS) increased autophagy by inhibition of glucose-6-phosphate dehydrogenase (G6PD) and inactivation of the pentose phosphate pathway (PPP). Previously, we suggested that cancer cells initially increase the glycolysis rate when encountering ROS, then the metabolic balance is changed from glycolysis to PPP, following the continuation of oxidative stress...

Protein kinases belong to the largest family of enzymes controlling every aspect of cellular activity including gene expression, cell division, differentiation and metabolism. They are part of major intracellular signalling pathways. Hence, it is not surprising that they are involved in the development of major diseases such as cardiovascular disorders, diabetes, dementia and, most importantly, cancer when they undergo mutations, modifications and unbalanced expression. This review will explore the possibility to draw a connection between the application of natural phytochemicals and the treatment of cancer...

Cisplatin (Cis) is an effective cancer therapy commonly employed in many therapeutic regimens. However, treatment regimens that contain either a high dose or cumulative doses of Cis could trigger liver damage. A unique study demonstrated that captopril (Cap) protects against Cis-induced liver toxicity, but only some liver function enzymes and some antioxidant enzymes were investigated in that study. Our study aims to elucidate the protective mechanism of Cap against Cis liver toxicity. Acute liver toxicity was induced in rats by injecting a single Cis dose (7...

PURPOSE: Mesothelioma is a terminal cancer caused by exposure to asbestos. As a cancer with a higher rate in men than women, women's experiences of living with mesothelioma are often underexplored. Furthermore, men's experiences are often taken for granted and therefore have remained underexplored. This paper considers men's and women's experiences across the mesothelioma pathway. METHODS: This qualitative study incorporated semi-structured interviews with 13 men and 11 women living with mesothelioma...

Neutrophils are conspicuous components of gastric cancer (GC) tumors, increasing with tumor progression and poor patient survival. However, the phenotype, regulation and clinical relevance of neutrophils in human GC are presently unknown. Most intratumoral neutrophils showed an activated CD54+ phenotype and expressed high level B7-H3. Tumor tissue culture supernatants from GC patients induced the expression of CD54 and B7-H3 on neutrophils in time-dependent and dose-dependent manners. Locally enriched CD54+ neutrophils and B7-H3+ neutrophils positively correlated with increased granulocyte-macrophage colony stimulating factor (GM-CSF) detection ex vivo; and in vitro GM-CSF induced the expression of CD54 and B7-H3 on neutrophils in both time-dependent and dose-dependent manners...

Tumor-induced lymphangiogenesis promotes tumor progression by generating new lymphatic vessels that helps in tumor dissemination to regional lymph nodes and distant sites. Recently, the role of Nectin-4 in cancer metastasis and angiogenesis has been studied, but its role in lymphangiogenesis is unknown. Here, we systematically delineated the role of Nectin-4 in lymphangiogenesis and its regulation in invasive duct carcinoma (IDC). Nectin-4 expression positively correlated with occurrence risk factors associated with breast cancer (alcohol, smoke, lifestyle habit, etc), CXCR4 expression, and LYVE-1-lymphatic vessel density (LVD)...

AIM: Hepatocellular carcinoma (HCC) is a highly invasive form of hepatic cancer. It is a highly intricate disease with multiple pathophysiological mechanisms underlying its pathogenesis. MATERIALS AND METHODS: The results of the current investigation shed light on the ability of saxagliptin (SAXA) (12.5 mg/kg) to defer HCC progression in an experimental model of thioacetamide (TAA)-induced hepatocarcinogenesis. RESULTS: SAXA administration improved liver function biomarkers, with a concomitant histopathological recovery...

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy that is characterized by early metastasis, low resectability, high recurrence, and therapy resistance. The experimental mouse models have played a central role in understanding the pathobiology of PDAC and in the preclinical evaluation of various therapeutic modalities. Different mouse models with targetable pathological hallmarks have been developed and employed to address the unique challenges associated with PDAC progression, metastasis, and stromal heterogeneity...

Pancreatic cancer remains an extremely deadly disease, with little improvement seen in treatment or outcomes over the last 40 years. Targeted monoclonal antibody therapy is one area that has been explored in attempts to tackle this disease. This review examines antibodies that have undergone clinical evaluation in pancreatic cancer. These antibodies target a wide variety of molecules, including tumour cell surface, stromal, immune and embryonic pathway targets. We discuss the therapeutic utility of these therapies both as monotherapeutics and in combination with other treatments such as chemotherapy...

Invasion of bladder cancer (BC) cells from the mucosa into the muscle layer is canonical for BC progression while phospholipase D isoform 1 (PLD1) is known to mediate development of cancer through phosphatidic acid (PA) production. We therefore used in silico, in vitro and in vivo approaches to detail the effect of PLD1 on BC invasion. In BC patients, higher levels of PLD1 expression were associated with poor prognoses. PLD1 knockdown significantly suppressed cellular invasion by human BC cells and matrix metalloproteinase-13 (MMP-13) was observed to mediate this effect...

Glioblastoma multiforme (GBM) is a severe form of brain cancer with an average five-year survival rate of 6.7%. Current treatment strategies include surgical resection of the tumor area and lining the lesion site with therapeutics, which offer only a moderate impact on increasing survival rates. Drug-testing models based on the monolayer cell culture method may partially explain the lack of advancement in effective GBM treatment, because this model is limited in its ability to show heterogeneous cell-cell and cell-environment interactions as tumor cells in the in vivo state...

OBJECTIVE: Poly(ADP-ribose) polymerase-1 (PARP1) interacts and poly(ADP-ribosyl)ates telomere repeat binding factor 2 (TRF2), which acts as a platform to recruit a large number of proteins at the telomere. Since the discovery of TRF2-SLX4 interaction, SLX4 is becoming the key player in telomere length (TL) maintenance and repair by telomere sister chromatid exchange (T-SCE). Defective TL maintenance pathway results in a spectrum of diseases called telomeropathies like dyskeratosis congenita, aplastic anemia, fanconi anemia, cancer...

17β-Hydroxysteroid dehydrogenase type 1 (17β-HSD1) and steroid sulfatase (STS) are involved in the synthesis of the most potent estrogen in the human body, estradiol (E2). These enzymes are known to play a pivotal role in the progression of estrogen-dependent diseases, such as breast cancer and endometriosis. Therefore, the inhibition of 17β-HSD1 and/or STS represents a promising avenue to modulate the growth of estrogen-dependent tumors or lesions. We recently established the key role of a bromoethyl side chain added at the C3-position of a 16β-carbamoyl-benzyl-E2 nucleus to covalently inhibit 17β-HSD1...

Numerous C-21 steroidal glycosides have been isolated from Cynanchum plants. Many of them derive from the aglycone caudatin (CDT) which includes a tetracyclic deacylmetaplexigenin unit and an ikemaoyl ester side chain. CDT can be found in diverse traditional medicines, such as Baishouwu radix used to treat gastro-intestinal disorders. The compound has revealed marked anticancer properties, reviewed here. CDT and its mono-glycoside analogue CDMC display antiproliferative activities against different cancer cell lines in vitro and have revealed significant anticancer effects in tumor xenograft models in vivo...