Intraperitoneal chemotherapy following neoadjuvant chemotherapy and optimal interval tumor reductive surgery for advanced ovarian cancer.

OBJECTIVES: Intraperitoneal (IP) chemotherapy following neoadjuvant chemotherapy (NACT) and interval tumor reductive surgery (TRS) for advanced ovarian cancer is feasible, however, the impact on disease outcomes remains unclear. We compare outcomes of patients treated with IP chemotherapy versus intravenous (IV) chemotherapy following NACT and interval TRS. METHODS: In this retrospective review, patients with advanced ovarian cancer were included if they received NACT followed by optimal interval TRS between 1/2004 and 4/2017. Patients were excluded if they had an ECOG PS >1, received >6 cycles of NACT or postoperative chemotherapy, and/or received bevacizumab during primary therapy. Primary outcomes were progression free survival (PFS) and overall survival (OS). RESULTS: There were 134 patients included in this study, 37 (28%) received IP and 97 (72%) received IV chemotherapy postoperatively. Patients in the IV group were older (median 66.3 vs 59.7 years, p = 0.0039) though there were no differences in BMI, race, BRCA status, stage, or histology. Median PFS was 3 months longer in the IP group (14.5 versus 11.5 months, p = 0.028) however there was no significant difference in OS. On univariate analysis, increasing number of NACT cycles (HR 1.914, 95% CI 1.024-3.497) and residual disease at completion of TRS (HR 1.541, 95% CI 1.042-2.248) were associated with decreased PFS; IP chemotherapy was associated with increased PFS (HR 0.633, 95% CI 0.414-0.944). These associations remained on multivariate analysis. Toxicity was comparable between the groups. CONCLUSIONS: IP after NACT and optimal interval TRS was associated with in improved PFS compared to IV chemotherapy without significant differences in toxicity.

94 ß-Decay Half-Lives of Neutron-Rich _{55}Cs to _{67}Ho: Experimental Feedback and Evaluation of the r-Process Rare-Earth Peak Formation.

The ß-decay half-lives of 94 neutron-rich nuclei ^{144-151}Cs, ^{146-154}Ba, ^{148-156}La, ^{150-158}Ce, ^{153-160}Pr, ^{156-162}Nd, ^{159-163}Pm, ^{160-166}Sm, ^{161-168}Eu, ^{165-170}Gd, ^{166-172}Tb, ^{169-173}Dy, ^{172-175}Ho, and two isomeric states ^{174m}Er, ^{172m}Dy were measured at the Radioactive Isotope Beam Factory, providing a new experimental basis to test theoretical models. Strikingly large drops of ß-decay half-lives are observed at neutron-number N=97 for _{58}Ce, _{59}Pr, _{60}Nd, and _{62}Sm, and N=105 for _{63}Eu, _{64}Gd, _{65}Tb, and _{66}Dy. Features in the data mirror the interplay between pairing effects and microscopic structure. r-process network calculations performed for a range of mass models and astrophysical conditions show that the 57 half-lives measured for the first time play an important role in shaping the abundance pattern of rare-earth elements in the solar system.

Highly spectrum-selective ultraviolet photodetector based on p-NiO/n-IGZO thin film heterojunction structure.

Ultraviolet photodetector with p-n heterojunction is fabricated by magnetron sputtering deposition of n-type indium gallium zinc oxide (n-IGZO) and p-type nickel oxide (p-NiO) thin films on ITO glass. The performance of the photodetector is largely affected by the conductivity of the p-NiO thin film, which can be controlled by varying the oxygen partial pressure during the deposition of the p-NiO thin film. A highly spectrum-selective ultraviolet photodetector has been achieved with the p-NiO layer with a high conductivity. The results can be explained in terms of the "optically-filtering" function of the NiO layer.

DNA metabarcoding of insects and allies: an evaluation of primers and pipelines.

Metabarcoding, the coupling of DNA-based species identification and high-throughput sequencing, offers enormous promise for arthropod biodiversity studies but factors such as cost, speed and ease-of-use of bioinformatic pipelines, crucial for making the leapt from demonstration studies to a real-world application, have not yet been adequately addressed. Here, four published and one newly designed primer sets were tested across a diverse set of 80 arthropod species, representing 11 orders, to establish optimal protocols for Illumina-based metabarcoding of tropical Malaise trap samples. Two primer sets which showed the highest amplification success with individual specimen polymerase chain reaction (PCR, 98%) were used for bulk PCR and Illumina MiSeq sequencing. The sequencing outputs were subjected to both manual and simple metagenomics quality control and filtering pipelines. We obtained acceptable detection rates after bulk PCR and high-throughput sequencing (80-90% of input species) but analyses were complicated by putative heteroplasmic sequences and contamination. The manual pipeline produced similar or better outputs to the simple metagenomics pipeline (1.4 compared with 0.5 expected:unexpected Operational Taxonomic Units). Our study suggests that metabarcoding is slowly becoming as cheap, fast and easy as conventional DNA barcoding, and that Malaise trap metabarcoding may soon fulfill its potential, providing a thermometer for biodiversity.

Breast milk DHA levels in Sri Lankan mothers vary significantly in three locations that have different access to dietary fish.

INTRODUCTION: Long-chain polyunsaturated fatty acids (LCPUFA) notably docosahexaenoeic acid (DHA) and arachidonic acid (ARA) are important for the optimum growth and development of the infant. DHA and ARA levels in breast-milk are thought to be influenced both by direct nutritional intake, and by the genetic variation of the FA desaturase enzymes. OBJECTIVES: To assess the fatty acid distribution in mothers' milk and their babies' blood, in three areas of Sri Lanka, with different access to sea-fish, and to see how the availability of dietary fish would affect fatty acid levels. METHODS: 6-12 week-old mother-baby pairs were recruited and mother's dietary intake assessed. Packed RBC from infants and breast milk (BM) from mothers were transported on dry ice to the Nutrition Laboratory, University of Otago, New Zealand for fatty acids extraction and quantification. RESULTS: We studied 136 mothers in three locations in Sri Lanka - Matara, Colombo, and Kandy. The breastmilk DHA levels were high in all three locations (0.79%, 0.53% and 0.37% respectively), and correlated with fish consumption. ARA levels did not vary significantly. In the 119 mother-infant pairs studied, infant erythrocyte DHA levels did not correlate significantly with BM DHA. CONCLUSIONS: Even the modest access to sea fish in the most inland site, resulted in BM-DHA levels higher than those found in any infant formula. Higher BM-DHA levels in the two other sites with greater access to fish did not lead to further increase in infant RBC-DHA levels. Where access to sea fish is limited, mothers should be encouraged to actively increase their fish intake as this would improve their DHA status, and also that of their breast milk.

Dynamics of wicking in silicon nanopillars fabricated with interference lithography and metal-assisted chemical etching.

The capillary rise of liquid on a surface, or "wicking", has potential applications in biological and industrial processes such as drug delivery, oil recovery, and integrated circuit chip cooling. This paper presents a theoretical study on the dynamics of wicking on silicon nanopillars based on a balance between the driving capillary forces and viscous dissipation forces. Our model predicts that the invasion of the liquid front follows a diffusion process and strongly depends on the structural geometry. The model is validated against experimental observations of wicking in silicon nanopillars with different heights synthesized by interference lithography and metal-assisted chemical etching techniques. Excellent agreement between theoretical and experimental results, from both our samples and data published in the literature, was achieved.

Effect of thermal annealing on the efficiency of heterojunction photovoltaic cells fabricated using poly(3-hexylthiophene) and methanofullerene, [6,6]-phenyl C61-butyric acid methyl ester.

The effects of thermal annealing on the efficiency of heterojunction photovoltaic (PV) cells that were fabricated using poly(3-hexylthiophene) (P3HT) and methanofullerene, [6,6]-phenyl C61-butyric acid methyl ester (PCBM) were investigated. The absorption spectra showed that the absorption intensity of the P3HT:PCBM layer that was annealed for 5 min had the highest value among the several samples with different annealing temperatures. The atomic force microscopy image showed that the P3HT:PCBM layer that was annealed for 5 min had the best surface morphology. The X-ray photoelectron spectroscopy demonstrated that the P3HT:PCBM layer that was annealed at 140 degrees C for 10 min enhanced the PCBM aggregation on the surface Al layer that was covered by the P3HT:PCBM layer. The efficiencies of the PV cells that were annealed at 3, 5, and 10 min were approximately 2.7, 4.2, and 3.5%, respectively. Based on the experiment results, the variations in the efficiency of the PV cells due their thermal treatment were described.

Radiofrequency ablation for 110 malignant liver tumours: preliminary results on percutaneous and surgical approaches.

BACKGROUND: Radiofrequency ablation (RFA) has been widely applied for the treatment of hepatocellular carcinoma and liver metastases. The reported mortality and morbidity rates are low. The aim of this study is to evaluate the safety and efficacy of RFA, and compare the results performed percutaneously versus surgically. PATIENTS AND METHODS: From 2003 to 2006, 79 patients with hepatic malignancies (59 hepatocellular carcinoma, 20 liver metastases) with a total of 110 lesions underwent RFA in our centre. Postablation assessment by CT scan was performed in all patients at 1-, 3- and 6-month intervals. Post-procedural complications, recurrence and survival were analysed. RESULTS: The patients' mean age was 60.0 years. In 46.8% of cases, we used a percutaneous approach; in 53.2% of cases, a surgical approach (8.9% laparoscopic; 44.3% open) was used if percutaneous approach was not feasible. The mean tumour size was 2.4 cm. Within the surgical group, 69% of patients received concomitant operative procedures such as cholecystectomy and hepatectomy. No treatment-related mortality was observed. Immediate complications occurred in five patients (6.3%), including gastric serosal burn (n = 1), ground pad superficial skin burn (n = 1), intra-abdominal bleeding (n = 2) and pleural effusion (n = 1). All patients except one attended subsequent follow-up, with a mean period of 16 months. Ablation was considered complete in 82.3% of patients (percutaneous approach 81.1%, surgical approach 83.3%, p = 0.72). Intrahepatic recurrence was observed in 52.3%, the majority of them located away from the RFA site. Extrahepatic recurrences were observed in 16.9% (percutaneous approach 16.7%, surgical approach 17.1%, p = 0.76). The overall one- and two-year survival rate was 93.7% and 74.4% respectively, and no statistically significant difference was observed between the two approaches. CONCLUSION: RFA is a safe and effective procedure for treating patients with malignant liver tumours. No difference in short term outcomes was observed between percutaneous and surgical approaches. A more prolonged follow-up study is required to assess longer-term outcomes.

Immunogenicity and safety profiles of genetic vaccines against human Her-2/neu in cynomolgus monkeys.

Her-2/neu is a well-characterized tumor-associated antigen, the overexpression of which in human carcinomas correlates with a poor prognosis. Here, we evaluated Her-2/neu-specific humoral and cellular immune responses in immunized monkeys after immunization with nonreplicating adenovirus (AdHM) expressing the extracellular and transmembrane domain of human Her-2/neu (HM) and/or naked DNA vaccine (pHM-hGM-CSF) expressing human granulocyte-macrophage colony-stimulating factor together with HM. Priming of monkeys with AdHM generated Her-2/neu-specific long-lasting antibody production. Furthermore, these Her-2/neu-specific antibodies produced by AdHM immunization, some of which shared epitope specificity with Herceptin, were able to induce antibody-dependent cellular cytotoxicity against Her-2-expressing target cells. Cellular immune responses were elicited in all monkeys immunized with Her-2/neu-expressing vaccine; interferon-gamma was secreted when these splenocytes were restimulated with Her-2/neu-expressing autologous cells, and immunization with AdHM induced Her-2/neu-specific lymphoproliferative responses. Further, immunization with pHM-hGM-CSF before AdHM immunization noticeably enhanced cytotoxic T-lymphocyte activity. In addition, we observed no abnormalities that would indicate that the genetic vaccines had toxic effects in the immunized monkeys. Thus, we can conclude that our genetic vaccines efficiently elicited Her-2/neu-specific humoral and cellular immune responses without causing severe adverse effects in nonhuman primates and that as such they warrant further clinical investigation.

Mode counting in high-dimensional orbital angular momentum entanglement.

We study the high-dimensional orbital angular momentum OAM) entanglement contained in the spatial profiles of two quantum-correlated photons. For this purpose, we use a multi-mode two-photon interferometer with an image rotator in one of the interferometer arms. By measuring the two-photon visibility as a function of the image rotation angle we measure the azimuthal Schmidt number, i.e., we count the number of OAM modes involved in the entanglement; in our setup this number is tunable from 1 to 8.

Protein tyrosine phosphatase phi regulates paxillin tyrosine phosphorylation and mediates colony-stimulating factor 1-induced morphological changes in macrophages.

Removal of colony-stimulating factor 1 (CSF-1) causes macrophages to round up and to increase their expression of protein tyrosine phosphatase phi (PTP phi). This is accompanied by the disruption of focal complexes and the formation of ruffles. Here we have overexpressed wild-type (WT) PTP phi and a phosphatase-inactive (C325S) mutant in a macrophage cell line in the presence and absence of CSF-1. In the presence of CSF-1, WT PTP phi induces cell rounding and ruffle formation, while C325S PTP phi has no effect. In contrast, in CSF-1-starved cells, C325S PTP phi behaves in a dominant negative fashion, preventing rounding and ruffling. Furthermore, C325S PTP phi increases adhesion in cycling cells, while WT PTP phi enhances motility. In WT PTP phi-overexpressing cells, the focal contact protein paxillin is selectively depleted from focal complexes and specifically dephosphorylated on tyrosine. In contrast, paxillin is hyperphosphorylated in C325S PTP phi-expressing cells. Moreover, a complex containing PTP phi, paxillin, and a paxillin-associated tyrosine kinase, Pyk2, can be immunoprecipitated from macrophage lysates, and the catalytic domain of PTP phi selectively binds paxillin and Pyk2 in vitro. Although PTP phi and Pyk2 do not colocalize with paxillin in focal complexes, all three proteins are colocalized in dorsal ruffles. The results suggest that paxillin is dephosphorylated by PTP phi in dorsal ruffles, using Pyk2 as a bridging molecule, resulting in a reduced pool of tyrosine-phosphorylated paxillin available for incorporation into focal complexes, thereby mediating CSF-1 regulation of macrophage morphology, adhesion, and motility.

Budd-Chiari-induced protein-losing enteropathy after liver transplantation.

Budd-Chiari syndrome (BCS) is one of the uncommon complications of hepatic venous reconstruction in liver transplantation. Protein-losing enteropathy (PLE) secondary to this event has rarely been described. A 14-year-old girl suffering from acute hepatic failure underwent an emergency living-related liver transplantation and developed BCS 1 year later. Her condition has been managed with several sessions of hepatic venoplasty. On one occasion, she suffered septicemia and severe diarrhea, passing large amount of fibrinoid material. The diagnosis of PLE was made clinically, which resolved immediately after reestablishment of hepatic venous patency by balloon venoplasty. This observation suggested that BCS was responsible for PLE in this patient. Prompt diagnosis and early intervention for this life-threatening condition is essential.

Germline p53 gene mutations in subsets of glioma patients.

BACKGROUND: Heritable germline mutations of the p53 gene have been described in patients with Li-Fraumeni syndrome, occasionally in nonfamilial malignancies such as multifocal osteosarcoma, in a small subgroup of young patients with two or more primary malignancies, and in patients with sporadic breast carcinoma. We recently reported that multifocal gliomas are frequently associated with other primary malignancies, and we hypothesized that genetic alterations may account for this phenomenon. PURPOSE: We examined the frequency of germline p53 gene mutations in patients with glioma and either multifocality of lesions, history of an additional primary (different) malignancy, or a family history of cancer. METHODS: Lymphocytes from 51 glioma patients were analyzed for germline p53 gene mutations using RNA-polymerase chain reaction analysis, single-strand conformation polymorphism, and gene sequencing techniques. RESULTS: Germline p53 gene mutations were detected in six of 19 patients with multifocal glioma, including two with family history of cancer, one with another primary malignancy, and two with all three risk factors; one of four patients with unifocal glioma, another primary malignancy, and a family history of cancer; and two of 15 patients with unifocal glioma and a family history of cancer but no second malignancies. No mutations were detected in the patient with unifocal glioma and another malignancy or in the 12 control patients with unifocal glioma and no second malignancies or family history of cancer. Patients having mutations were younger than other patients in the same group. CONCLUSIONS: Germline p53 mutations are frequent in patients with multifocal glioma, glioma and another primary malignancy, and glioma associated with a family history of cancer, particularly if these factors are combined. IMPLICATIONS: Relatives at high risk can be identified for genetic counseling, early cancer detection, and possible enrollment in chemoprevention trials.

Heterogeneity in induced heat resistance and its relation to synthesis of stress proteins in rat tumor cell clones.

Tumor cell clones isolated from a rat 13762NF mammary adenocarcinoma and its spontaneous metastases were heterogeneous in their survival responses to continuous 42 degrees heating. Clones MTLn3 and MTF7 had similar initial survival responses; they were significantly less sensitive than clone MTC. Following the first decrease in survival, different magnitudes of induced thermal resistance were observed. When ratios of the first and resistant slopes of survival curves were compared (the thermotolerance ratio), the order of induced thermal resistance was MTLn3 greater than MTF7 greater than MTC. These clones were compared for the rates of synthesis of heat stress proteins (HSP). The same four major HSP at Mr 112,000, 90,000, 70,000, and 22,000 were induced or enhanced in all 3 clones. The rates of synthesis of these HSP were analyzed through a unique system of computer-assisted video densitometry and digitization. When all 4 HSP were analyzed as a group, the rates were significantly different (p less than 0.017), and the rank order of rates of synthesis was significant with MTLn3 greater than MTF7 greater than MTC. Induction kinetics of the individual HSP were different. Individually, the HSP at Mr 112,000, 90,000, and 22,000 were synthesized at significantly different rates between clones (p less than 0.001) but the Mr 70,000 HSP was not. Absolute total protein synthesis was highest for clone MTLn3, and MTF7 was higher than MTC but only marginally. Although absolute accumulations of these HSP could not be directly compared between these clones, the higher rates of HSP synthesis in these tumor cell clones correlated with more thermal resistance. These data support the working hypothesis that one or more of these HSP have a direct role in the mechanism(s) for inducing thermal resistance in rat tumor cells, but other factors such as total protein synthesis could modify the complex bio-chemical and phenotypic pathways involved in induced HSP and thermal resistance.

Cacidases: caspases can cleave after aspartate, glutamate and phosphoserine residues.

Caspases are a family of proteases found in all metazoans, including a dozen in humans, that drive the terminal stages of apoptosis as well as other cellular remodeling and inflammatory events. Caspases are named because they are cysteine class enzymes shown to cleave after aspartate residues. In the past decade, we and others have developed unbiased proteomic methods that collectively identified ~2000 native proteins cleaved during apoptosis after the signature aspartate residues. Here, we explore non-aspartate cleavage events and identify 100s of substrates cleaved after glutamate in both human and murine apoptotic samples. The extended consensus sequence patterns are virtually identical for the aspartate and glutamate cleavage sites suggesting they are cleaved by the same caspases. Detailed kinetic analyses of the dominant apoptotic executioner caspases-3 and -7 show that synthetic substrates containing DEVD↓ are cleaved only twofold faster than DEVE↓, which is well within the 500-fold range of rates that natural proteins are cut. X-ray crystallography studies confirm that the two acidic substrates bind in virtually the same way to either caspases-3 or -7 with minimal adjustments to accommodate the larger glutamate. Lastly, during apoptosis we found 121 proteins cleaved after serine residues that have been previously annotated to be phosphorylation sites. We found that caspase-3, but not caspase-7, can cleave peptides containing DEVpS↓ at only threefold slower rate than DEVD↓, but does not cleave the unphosphorylated serine peptide. There are only a handful of previously reported examples of proteins cleaved after glutamate and none after phosphorserine. Our studies reveal a much greater promiscuity for cleaving after acidic residues and the name 'cacidase' could aptly reflect this broader specificity.

Detection of cellular proteins that interact with the NF2 tumor suppressor gene product.

The neurofibromatosis type 2 (NF2) gene was recently cloned, and the protein it encodes (merlin) was revealed to belong to a family of proteins that link cytoskeletal components with proteins in the cell membrane. To elucidate the biological function of merlin, we produced a bacterial fusion protein consisting of glutathione S-transferase and merlin and used it to detect five merlin-binding cellular proteins, designated p165, p145, p125, p85 and p70, by a protein-binding assay. p165 and merlin were phosphorylated on serine/threonine residues, and immunoprecipitation showed that p85 bound the native form of merlin. Although the entire merlin-ezrin-radixin-moesin (MERM) homology domain of merlin was found to be essential for binding to all five proteins, the MERM homology domains of ezrin and moesin did not bind to any of the five proteins. Since most reported NF2 mutations are in the region we determined was necessary for binding, the mutations probably impair binding. Therefore, the formation of the protein complex is probably crucial for tumor suppression.