Suppression of colorectal cancer cell growth by combined treatment of 6-gingerol and γ-tocotrienol via alteration of multiple signalling pathways

This study aimed to identify and elucidate molecular mechanisms involved in the suppression of SW837 colorectal cancer cells modulated by combined tre atment of γ-tocotrienol and 6-gingerol. Total RNA from both untreated and treated cells was prepared for transcriptome analysis using RNA sequencing techniques. We performed high-throughput sequencing at approximately 30–60 million coverage on both untreated and 6G + γT3-treated cells. The results showed that cancer-specific differential gene expression occurred and functional enrichment pathway analysis suggested that more than one pathway was modulated in 6G + γT3-treated cells. Combined treatment with 6G + γT3 augmented its chemotherapeutic effect by interfering with the cell cycle process, downregulating the Wnt signalling pathway and inducing apoptosis mainly through caspase-independent programmed cell death through mitochondrial dysfunction, activation of ER-UPR, disruption of DNA repair mechanisms and inactivation of the cell cycle process through the downregul ation of main genes in proliferation such asFOXM1 and its downstream genes. The combined treatment exerted its cytotoxic effect through upregulation of genes in stress response activation and cytostatic effects demonstrated by downregulation of main regulator genes in the cell cycle. Selected genes involved in particular pathways includingATF6,DDIT3,GADD34,FOXM1,CDK1 andp21 displayed conc...
Source: Journal of Natural Medicines - Category: Drugs & Pharmacology Source Type: research

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ConclusionsSporadic dMMR breast cancers are extremely rare (Davies et al. in Cancer Res 77:4755 –4762, 2017). It seems reasonable to conclude that identifying a dMMR breast cancer in a patient with known LS strongly suggests that her LS is breast cancer-predisposing. LS patients with dMMR breast cancers might therefore be considered for above-average breast cancer screening for the developme nt of additional breast cancers. Also, the FDA recently granted approval of checkpoint inhibitor therapy for all metastatic dMMR solid malignancies (Lemery et al. in N Engl J Med 377:1409–1412, 2017). MMR expression assays ...
Source: Breast Cancer Research and Treatment - Category: Cancer & Oncology Source Type: research
AbstractBackground.Alterations in the DNA damage response (DDR) pathway confer sensitivity to certain chemotherapies, radiation, and other DNA damage repair targeted therapies. BRCA1/2 are the most well‐studied DDR genes, but recurrent alterations are described in other DDR pathway members across cancers. Deleterious DDR alterations may sensitize tumor cells to poly (ADP‐ribose) polymerase inhibition, but there are also increasing data suggesting that there may also be synergy with immune checkpoint inhibitors. The relevance of DDR defects in gastrointestinal (GI) cancers is understudied. We sought to characterize DDR...
Source: The Oncologist - Category: Cancer & Oncology Authors: Tags: Gastrointestinal Cancer Source Type: research
ConclusionTo optimize targeting and visualization of the surgical field in right pelvic sidewall/paracolic gutter, robotic arms can be placed in a straight line from above the pubic symphysis extending to the left subcostal line and between the midline vertical and midclavicular lines. Robotic tumor debulking should be considered in selected patients with recurrent ovarian cancer who present with oligo-metastatic disease, in the absence of carcinomatosis.
Source: Journal of Minimally Invasive Gynecology - Category: OBGYN Source Type: research
ConclusionSacrospinous ligament suspension for the correction of massive vaginal vault prolapse utilizing PEEK anchors and porcine urinary bladder extracellular matrix is a reasonable alternative to transvaginal synthetic mesh repairs.Advantages to this vaginal approach include: 1) Avoidance of laparoscopic risks in a patient with massive ascites, 2) Avoidance of chronic pain, erosion and extrusion associated with synthetic mesh.
Source: Journal of Minimally Invasive Gynecology - Category: OBGYN Source Type: research
Condition:   Colorectal Cancer Interventions:   Drug: Regorafenib (BAY73-4506, Stivarga);   Biological: Nivolumab (Opdivo) Sponsors:   Bayer;   Bristol-Myers Squibb Not yet recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Tougeron Tumor DNA mismatch repair (MMR) deficiency testing is important to the identification of Lynch syndrome and decision making regarding adjuvant chemotherapy in stage II colorectal cancer (CRC) and has become an indispensable test in metastatic tumors due to the high efficacy of immune checkpoint inhibitor (ICI) in deficient MMR (dMMR) tumors. CRCs greatly benefit from this testing as approximately 15% of them are dMMR but only 3% to 5% are at a metastatic stage. MMR status can be determined by two different methods, microsatellite instability (MSI) testing on tumor DNA, and immunohistochemistry of the MMR pro...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
ConclusionMSI has the potential to become a key predictor for evaluating the degree of malignancy, efficacy and prognosis of tumours. Clinically, MSI patterns will provide more valuable information for clinicians to create optimal individualized treatment strategies based on frameshift peptides vaccines.
Source: Journal of Cancer Research and Clinical Oncology - Category: Cancer & Oncology Source Type: research
AbstractBackgroundWe previously reported that in pathogenic mismatch repair (path_MMR) variant carriers, the incidence of colorectal cancer (CRC) was not reduced when colonoscopy was undertaken more frequently than once every 3 years, and that CRC stage and interval since last colonoscopy were not correlated.MethodsThe Prospective Lynch Syndrome Database (PLSD) that records outcomes of surveillance was examined to determine survival after colon cancer in relation to the time since previous colonoscopy and pathological stage. Onlypath_MMR variants scored by the InSiGHT variant database as class 4 or 5 (clinically actionable...
Source: Hereditary Cancer in Clinical Practice - Category: Cancer & Oncology Source Type: research
Colorectal cancer is a heterogeneous disease that develops via stepwise accumulation of well-characterized genetic and epigenetic alterations. We review the genetic changes associated with the development of pre-cancerous colorectal adenomas and their progression to tumors, as well as the effects of defective DNA repair, chromosome instability, microsatellite instability, and alterations in the serrated pathway and DNA methylation. We provide insights into the different molecular subgroups of colorectal tumors that develop via each of these different mechanisms and their associations with patient outcomes.
Source: Gastroenterology - Category: Gastroenterology Authors: Source Type: research
CONCLUSION: This study highlights the distinct clinicopathological features of MSI-related CRC and the relevance of MSI testing of stage II CRC for management decisions and prognostication.
Source: Indian Journal of Cancer - Category: Cancer & Oncology Authors: Source Type: research
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