- Bevacizumab improves overall survival in platinum refractory ovarian cancer patients: A retrospective study. [Journal Article]
- TJTaiwan J Obstet Gynecol 2018; 57(6):819-824
- CONCLUSIONS: Our findings may potentially aid in developing treatment strategies for platinum-refractory patients with poor prognoses.
- Interpretation of Euphorbia Kansui Stir-Fried with Vinegar Treating Malignant Ascites by a UPLC-Q-TOF/MS Based Rat Serum and Urine Metabolomics Strategy Coupled with Network Pharmacology. [Journal Article]
- MMolecules 2018 Dec 07; 23(12)
- Euphorbia kansui stir-fried with vinegar (V-kansui) has promising biological activities toward treating malignant ascites with reduced toxicity compared to crude kansui. But the mechanism concerning ...
Euphorbia kansui stir-fried with vinegar (V-kansui) has promising biological activities toward treating malignant ascites with reduced toxicity compared to crude kansui. But the mechanism concerning promoting the excretion of ascites has not been systematically studied. The purpose of this paper was to investigate the possible mechanism of V-kansui in treating malignant ascites, including metabolic pathways and molecular mechanism using an integrated serum and urine metabolomics coupled with network pharmacology. Serum and urine samples of rats were collected and analyzed by ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS). A comparison with crude kansui was also made to demonstrate the feasibility of processing. Principle component analysis (PCA) and orthogonal partial least square discriminate analysis (OPLS-DA) were conducted to discriminate the groups, search important variables and reveal the possible pathways. A compound-target-metabolite network was finally constructed to identify the crucial targets to further understand the molecular mechanism. Sixteen significant metabolites contributing to the discrimination of model and control groups were tentatively screened out. They were mainly involved in the arachidonic acid metabolism, steroid hormone biosynthesis and primary bile acid to possibly reduce inflammatory and modulate the renin-angiotensin-aldosterone system to achieve treating malignant ascites. A bio-network starting from the compounds and ending in the metabolites was constructed to elucidate the molecular mechanism. HSP90AA1, ANXA2, PRDX6, PCNA, SOD2 and ALB were identified as the potential key targets that were responsible for the treatment of malignant ascites by the parameter combining the average shortest path length and betweenness centrality. The correlated 17 compounds were considered as the potential active ingredients in V-kansui. In addition, the metabolomics showed that the effect of V-kansui was almost in accordance with crude kansui. These results systematically revealed the mechanism of V-kansui against malignant ascites for the first time using metabolomics coupled with network pharmacology. V-kansui could be a promising safe and therapeutic medicine for the excretion of ascites.
- Activation of LXRɑ/β by cholesterol in malignant ascites promotes chemoresistance in ovarian cancer. [Journal Article]
- BCBMC Cancer 2018 Dec 10; 18(1):1232
- CONCLUSIONS: High cholesterol in malignant ascites contributes to poor prognosis in ovarian cancer patients, partly by contributing to multidrug resistance through upregulation of MDR1 via activation of LXRɑ/β.
- Permanent peritoneal ports for the management of recurrent malignant ascites: a retrospective review of safety and efficacy. [Journal Article]
- IMIntern Med J 2018; 48(12):1524-1528
- Large volume paracentesis is effective in relieving the symptoms of malignant ascites, but frequent procedures are often required. Permanent peritoneal ports are an alternative to repeated procedures...
Large volume paracentesis is effective in relieving the symptoms of malignant ascites, but frequent procedures are often required. Permanent peritoneal ports are an alternative to repeated procedures. We describe our experience with the use of peritoneal ports in patients at Middlemore Hospital (Auckland, New Zealand) who had a port inserted for the drainage of malignant ascites. Twenty-eight ports were inserted in 26 patients and accessed a total of 257 times with acceptably low rates of complications including cellulitis, peritonitis and wound dehiscence.
- GPx3 supports ovarian cancer progression by manipulating the extracellular redox environment. [Journal Article]
- RBRedox Biol 2018 Nov 17
- Ovarian cancer remains the most lethal gynecologic malignancy, and is primarily diagnosed at late stage when considerable metastasis has occurred in the peritoneal cavity. At late stage abdominal cav...
Ovarian cancer remains the most lethal gynecologic malignancy, and is primarily diagnosed at late stage when considerable metastasis has occurred in the peritoneal cavity. At late stage abdominal cavity ascites accumulation provides a tumor-supporting medium in which cancer cells gain access to growth factors and cytokines that promote survival and metastasis. However, little is known about the redox status of ascites, or whether antioxidant enzymes are required to support ovarian cancer survival during transcoelomic metastasis in this medium. Gene expression cluster analysis of antioxidant enzymes identified two distinct populations of high-grade serous adenocarcinomas (HGSA), the most common ovarian cancer subtype, which specifically separated into clusters based on glutathione peroxidase 3 (GPx3) expression. High GPx3 expression was associated with poorer overall patient survival and increased tumor stage. GPx3 is an extracellular glutathione peroxidase with reported dichotomous roles in cancer. To further examine a potential pro-tumorigenic role of GPx3 in HGSA, stable OVCAR3 GPx3 knock-down cell lines were generated using lentiviral shRNA constructs. Decreased GPx3 expression inhibited clonogenicity and anchorage-independent cell survival. Moreover, GPx3 was necessary for protecting cells from exogenous oxidant insult, as demonstrated by treatment with high dose ascorbate. This cytoprotective effect was shown to be due to GPx3-dependent removal of extracellular H2O2. Importantly, GPx3 was necessary for clonogenic survival when cells were cultured in patient-derived ascites fluid. While oxidation reduction potential (ORP) of malignant ascites was heterogeneous in our patient cohort, and correlated positively with ascites iron content, GPx3 was required for optimal survival regardless of ORP or iron content. Collectively, our data suggest that HGSA ovarian cancers cluster into distinct groups of high and low GPx3 expression. GPx3 is necessary for HGSA ovarian cancer cellular survival in the ascites tumor environment and protects against extracellular sources of oxidative stress, implicating GPx3 as an important adaptation for transcoelomic metastasis.
- Management of malignancy-associated bowel obstruction by cervical esophagostomy and total parenteral nutrition, case series of 2 patients. [Journal Article]
- IJInt J Surg Case Rep 2018 Nov 16; 53:390-393
- CONCLUSIONS: Long-term management of malignancy-associated bowel obstruction is possible with improvement in quality of life using a combination of TPN and a cervical esophagostomy tube. In these two cases the cervical esophagostomy tube was placed with limited adverse events, and adequate drainage of intestinal secretions long-term.
- Biochemical Analysis of Pleural Fluid and Ascites. [Review]
- CBClin Biochem Rev 2018; 39(2):39-50
- Biochemical testing of peritoneal and pleural fluids is carried out widely, although the range of tests likely to be useful is limited in comparison to the repertoire of tests available in a modern b...
Biochemical testing of peritoneal and pleural fluids is carried out widely, although the range of tests likely to be useful is limited in comparison to the repertoire of tests available in a modern biochemistry laboratory. Fluids accumulate when pathological processes cause an imbalance between hydrostatic pressure gradients, capillary membrane permeability and lymphatic capacity, resulting in protein-poor transudates or inflammatory exudates. In peritoneal fluid, albumin is the most useful test, for the calculation of the serum-ascites albumin gradient; protein and LDH have a role regarding risk and diagnosis of spontaneous bacterial peritonitis and amylase may be useful in diagnosing fluid accumulation due to pancreatitis. Peritoneal fluid pH and glucose are not indicated analyses. For pleural fluid, protein and LDH are important in distinguishing between transudate and exudate using Light's criteria; albumin and the serum-effusion albumin gradient may have a complementary role in patients already on diuretics. Pleural fluid pH is the most useful marker of infection although LDH and glucose are also used. Pleural fluid amylase is often measured but, if raised, is more likely to reflect a malignant process than pancreatic disease as the former is much more prevalent. Tumour markers in both peritoneal and pleural fluids generally have limited diagnostic accuracy for detecting local malignancy. Limited studies validating standard serum test methods for use with pleural and peritoneal fluids have been published but work is progressing in this area both in Australasia and overseas and opportunities exist for contributing to this effort.
- Peritoneal carcinomatosis in colorectal cancer: Defining predictive factors for successful cytoreductive surgery and hyperthermic intraperitoneal chemotherapy - A pilot study. [Journal Article]
- JEJ Egypt Natl Canc Inst 2018; 30(4):143-150
- CONCLUSIONS: In patients with PC-CRC, malignant ascites and PCI > 20 are poor prognostic factors associated with failure to accomplish CRS with consequent poor survival.
- Effect of the BH3 Mimetic Polyphenol (-)-Gossypol (AT-101) on the in vitro and in vivo Growth of Malignant Mesothelioma. [Journal Article]
- FPFront Pharmacol 2018; 9:1269
- Malignant mesothelioma (MM) is a primary tumor arising from mesothelial cells. The survival of MM patients following traditional chemotherapy is poor, thus innovative treatments for MM are needed. (-...
Malignant mesothelioma (MM) is a primary tumor arising from mesothelial cells. The survival of MM patients following traditional chemotherapy is poor, thus innovative treatments for MM are needed. (-)-gossypol (AT-101) is a BH3 mimetic compound which possesses anti-tumoral activity by targeting multiple signaling transduction pathways. Several clinical trials employing AT-101 have been performed and some of them are still ongoing. Accordingly, we investigated the in vitro effects of AT-101 on cell proliferation, cell cycle regulation, pro-survival signaling pathways, apoptosis and autophagy of human (MM-B1, H-Meso-1, and MM-F1) and mouse (#40a) MM cell lines. In addition, we explored the in vivo anti-tumor activities of AT-101 in a mouse model, in which the transplantation of MM cells induces ascites in the peritoneal space. AT-101 inhibited in vitro MM cells survival in a dose- and time-dependent manner and triggered autophagy, but the process was then blocked and was coincident with apoptosis activation. To confirm the effect of AT-101 in inducing the apoptosis of MM cells, MM cells were simultaneously treated with AT-101 and with the caspase inhibitor, Z-VAD-FMK. Z-VAD-FMK was able to significantly reduce the number of cells in the subG1 phase compared to the treatment with AT-101 alone. This result corroborates the induction of cell death by apoptosis following treatment with AT-101. Indeed, Western blotting results showed that AT-101 increases Bax/Bcl-2 ratio, modulates p53 expression, activates caspase 9 and the cleavage of PARP-1. In addition, the treatment with AT-101 was able to: (a) decrease the ErbB2 protein expression; (b) increase the EGFR protein expression; (c) affect the phosphorylation of ERK1/2, p38 and AKT; (d) stimulate JNK1/2 and c-jun phosphorylation. Our in vivo results showed that the intraperitoneal administration of AT-101 increased the median survival of C57BL/6 mice intraperitoneally transplanted with #40a cells and reduced the risk of developing tumors. Our findings may have important implications for the design of MM therapies by employing AT-101 as an anticancer agent in combination with standard therapies.
New Search Next
- Author Correction: Evaluating Tumor Evolution via Genomic Profiling of Individual Tumor Spheroids in a Malignant Ascites. [Published Erratum]
- SRSci Rep 2018 Nov 21; 8(1):17395
- A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.