Changes in ovarian cancer survival during the 20years before the era of targeted therapy

Background The survival of patients with ovarian cancer has improved because of surgery and chemotherapy. This study aimed to estimate the changes in survival rates among Korean women with ovarian cancer prior to the introduction of targeted therapy for ovarian cancer. Methods Data were obtained from the Korea Central Cancer Registry regarding patients who were diagnosed with epithelial ovarian cancer between 1995 and 2014. The relative survival rates were calculated for 5-year periods using the Ederer II method. Cox proportional hazard models were created to assess the associations of demographic and clinicopathological factors with ovarian cancer survival. Results During the study period, 22,880 women were diagnosed with epithelial ovarian cancer. The 5-year relative survival rate improved from 57.2% during 1995–1999 to 63.8% during 2010–2014 (P < 0.001). Survival outcomes improved between 1995 and 1999 and 2010–2014 for the serous and endometrioid carcinoma subtypes (P < 0.001). However, no improvements were observed for the mucinous and clear cell carcinoma subtypes (P = 0.189 and P = 0.293, respectively). Multivariate analysis revealed that younger age, early stage, recent diagnosis, primary surgical treatment, and non-serous histological subtype were favorable prognostic factors. Conclusion Survival outcomes have improved for serous and endometrioid epithelial ovarian cancer in the last 20years. However, no improvement was observed for patients with mucinous and clear cell carcinoma subtypes.This study was supported in part by a National Cancer Center Grant (Grant No. NCC-1610200) and a new faculty research seed money grant of Yonsei University College of Medicine for 2017 (Grant No. 2017–32-0033). The funding bodies played no role in the design and conduct of the study; collection, analysis, and interpretation of data; writing of the manuscript, and the decision to submit the manuscript for publication

Diode Laser—Can It Replace the Electrical Current Used in Endoscopic Submucosal Dissection?

Background/Aims A new medical fiber-guided diode laser system (FDLS) is expected to offer high-precision cutting with simultaneous hemostasis. Thus, this study aimed to evaluate the feasibility of using the 1,940-nm FDLS to perform endoscopic submucosal dissection (ESD) in the gastrointestinal tract of an animal model. Methods In this prospective animal pilot study, gastric and colorectal ESD using the FDLS was performed in ex vivo and in vivo porcine models. The completeness of en bloc resection, the procedure time, intraprocedural bleeding, histological injuries to the muscularis propria (MP) layer, and perforation were assessed. Results The en bloc resection and perforation rates in the ex vivo study were 100% (10/10) and 10% (1/10), respectively; those in the in vivo study were 100% (4/4) and 0% for gastric ESD and 100% (4/4) and 25% (1/4) for rectal ESD, respectively. Deep MP layer injuries tended to occur more frequently in the rectal than in the gastric ESD cases, and no intraprocedural bleeding occurred in either group. Conclusions The 1,940-nm FDLS was capable of yielding high en bloc resection rates without intraprocedural bleeding during gastric and colorectal ESD in animal models

A Case of Non-Functioning Huge Adrenocortical Carcinoma Extending Into Inferior Vena Cava and Right Atrium

Primary adrenocortical carcinoma (ACC) is a rare tumor and its usual sites of metastasis are the lung (71%), lymph node (68%), liver (42%), and bone (26%). However, intracaval invasion extending into the right atrium is very rare and spontaneous regression of tumor burden in adrenal carcinoma is also rare. We report a case of ACC with direct invasion of the inferior vena cava and right atrium. A 34-yr-old male patient presented with progressive dyspnea, weight loss, and poor oral intake over 3 months. Non-functioning ACC with direct invasion of the inferior vena cava and right atrium was confirmed by imaging, pathologic, and hormonal study. Chemo-radio-therapy was attempted. However, tumor burden was not changed, but rather toxic hepatitis and thrombocytopenia were developed. His subjective symptoms and general conditions were improved after 1 month of conservative management and the patient was discharged. During clinical follow-up, this tumor showed spontaneous regression

Lycopene Inhibits Oxidative Stress-Mediated Inflammatory Responses in Ethanol/Palmitoleic Acid-Stimulated Pancreatic Acinar AR42J Cells

High alcohol intake results in the accumulation of non-oxidative ethanol metabolites such as fatty acid ethyl esters (FAEEs) in the pancreas. High FAEE concentrations mediate pancreatic acinar cell injury and are associated with alcoholic pancreatitis. Treatment with ethanol and the fatty acid palmitoleic acid (EtOH/POA) increased the levels of palmitoleic acid ethyl ester and induced zymogen activation and cytokine expression in pancreatic acinar cells. EtOH/POA induces nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-mediated reactive oxygen species (ROS) production and pancreatic acinar cell injury. Lycopene, a bright-red carotenoid, is a potent antioxidant due to its high number of conjugated double bands. This study aimed to investigate whether lycopene inhibits the EtOH/POA-induced increase in ROS production, zymogen activation, and expression of the inflammatory cytokine IL-6 in EtOH/POA-stimulated pancreatic acinar AR42J cells. EtOH/POA increased the ROS levels, NADPH oxidase and NF-κB activities, zymogen activation, IL-6 expression, and mitochondrial dysfunction, which were inhibited by lycopene. The antioxidant N-acetylcysteine and NADPH oxidase 1 inhibitor ML171 suppressed the EtOH/POA-induced increases in ROS production, NF-κB activation, zymogen activation, and IL-6 expression. Therefore, lycopene inhibits EtOH/POA-induced mitochondrial dysfunction, zymogen activation, and IL-6 expression by suppressing NADPH oxidase-mediated ROS production in pancreatic acinar cells

Lycopene Inhibits Reactive Oxygen Species-Mediated NF-κB Signaling and Induces Apoptosis in Pancreatic Cancer Cells

Generation of excess quantities of reactive oxygen species (ROS) caused by mitochondrial dysfunction facilitates rapid growth of pancreatic cancer cells. Elevated ROS levels in cancer cells cause an anti-apoptotic effect by activating survival signaling pathways, such as NF-&#954;B and its target gene expression. Lycopene, a carotenoid found in tomatoes and a potent antioxidant, displays a protective effect against pancreatic cancer. The present study was designed to determine if lycopene induces apoptosis of pancreatic cancer PANC-1 cells by decreasing intracellular and mitochondrial ROS levels, and consequently suppressing NF-&#954;B activation and expression of NF-&#954;B target genes including cIAP1, cIAP2, and survivin. The results show that the lycopene decreased intracellular and mitochondrial ROS levels, mitochondrial function (determined by the mitochondrial membrane potential and oxygen consumption rate), NF-&#954;B activity, and expression of NF-&#954;B-dependent survival genes in PANC-1 cells. Lycopene reduced cell viability with increases in active caspase-3 and the Bax to Bcl-2 ratio in PANC-1 cells. These findings suggest that supplementation of lycopene could potentially reduce the incidence of pancreatic cancer

Astaxanthin Inhibits Oxidative Stress-Induced Ku Protein Degradation and Apoptosis in Gastric Epithelial Cells

Oxidative stress induces DNA damage which can be repaired by DNA repair proteins, such as Ku70/80. Excess reactive oxygen species (ROS) stimulate the activation of caspase-3, which degrades Ku 70/80. Cells with decreased Ku protein levels undergo apoptosis. Astaxanthin exerts antioxidant activity by inducing the expression of catalase, an antioxidant enzyme, in gastric epithelial cells. Therefore, astaxanthin may inhibit oxidative stress-induced DNA damage by preventing Ku protein degradation and thereby suppressing apoptosis. Ku proteins can be degraded via ubiquitination and neddylation which adds ubiquitin-like protein to substrate proteins. We aimed to determine whether oxidative stress decreases Ku70/80 expression through the ubiquitin&ndash;proteasome pathway to induce apoptosis and whether astaxanthin inhibits oxidative stress-induced changes in gastric epithelial AGS cells. We induced oxidative stress caused by the treatment of &beta;-D-glucose (G) and glucose oxidase (GO) in the cells. As a result, the G/GO treatment increased ROS levels, decreased nuclear Ku protein levels and Ku-DNA-binding activity, and induced the ubiquitination of Ku80. G/GO increased the DNA damage marker levels (&gamma;-H2AX; DNA fragmentation) and apoptosis marker annexin V-positive cells and cell death. Astaxanthin inhibited G/GO-induced alterations, including Ku degradation in AGS cells. MLN4924, a neddylation inhibitor, and MG132, a proteasome inhibitor, suppressed G/GO-mediated DNA fragmentation and decreased cell viability. These results indicated that G/GO-induced oxidative stress causes Ku protein loss through the ubiquitin&ndash;proteasome pathway, resulting in DNA fragmentation and apoptotic cell death. Astaxanthin inhibited oxidative stress-mediated apoptosis via the reduction of ROS levels and inhibition of Ku protein degradation. In conclusion, dietary astaxanthin supplementation or astaxanthin-rich food consumption may be effective for preventing or delaying oxidative stress-mediated cell damage by suppressing Ku protein loss and apoptosis in gastric epithelial cells

Docoxahexaenoic Acid Induces Apoptosis of Pancreatic Cancer Cells by Suppressing Activation of STAT3 and NF-κB

The &#969;3-polyunsaturated fatty acid docosahexenoic acid (DHA) is known to induce apoptosis of cancer cells. In this study, DHA was shown to reduce viability of pancreatic cancer cells (PANC-1) by inducing DNA fragmentation, activating caspase-3, and increasing the ratio of Bax/Bcl-2. To determine the DHA mechanism of action, the impact of DHA on the activation of the key signaling proteins epidermal growth factor receptor (EGFR), signal transducer and activator of transcription factor 3 (STAT3), nuclear transcription factor-&#954;B (NF-&#954;B), and I&#954;B&#945; in PANC-1 cells was probed. The observed DHA suppression of NF-&#954;B DNA-binding activity was found to result from reduced I&#954;B&#945; phosphorylation. The observed DHA-induced suppression of STAT3 activation was found to be the result of suppressed EGFR activation, which derives from the inhibitory effect of DHA on the integrity of localization of EGFR to cell membrane lipid rafts. Since the activation of STAT3 and NF-&#954;B mediates the expression of survival genes cyclin D1 and survivin, DHA induced apoptosis by suppressing the STAT3/NF-&#954;B-cyclin D1/survivin axis. These results support the proposal that DHA-induced apoptosis of pancreatic cells occurs via disruption of key pro-cell survival signaling pathways. We suggest that the consumption of DHA-enriched foods could decrease the incidence of pancreatic cancer