Nadir CA-125 level as prognosis indicator of high-grade serous ovarian cancer

PURPOSE: The capacity of nadir CA-125 levels to predict the prognosis of epithelial ovarian cancer remains controversial. This study aimed to explore whether the nadir CA-125 serum levels could predict the durations of overall survival (OS) and progression free survival (PFS) in patients with high-grade serous ovarian cancer (HG-SOC) from the USA and PRC. MATERIALS AND METHODS: A total of 616 HG-SOC patients from the MD Anderson Cancer Center (MDACC, USA) between 1990 and 2011 were retrospectively analyzed. The results of 262 cases from the Jiangsu Institute of Cancer Research (JICR, PRC) between 1992 and 2011 were used to validate the MDACC data. The CA-125 immunohistochemistry assay was performed on 280 tissue specimens. The Cox proportional hazards model and the log-rank test were used to assess the associations between the clinicopathological characteristics and duration of survival. RESULTS: The nadir CA-125 level was an independent predictor of OS and PFS (p < 0.01 for both) in the MDACC patients. Lower nadir CA-125 levels (≤10 U/mL) were associated with longer OS and PFS (median: 61.2 and 16.8 months with 95% CI: 52.0–72.4 and 14.0–19.6 months, respectively) than their counterparts with shorter OS and PFS (median: 49.2 and 10.5 months with 95% CI: 41.7–56.7 and 6.9–14.1 months, respectively). The nadir CA-125 levels in JICR patients were similarly independent when predicting the OS and PFS (p < 0.01 for both). Nadir CA-125 levels less than or equal to 10 U/mL were associated with longer OS and PFS (median: 59.9 and 15.5 months with 95% CI: 49.7–70.1 and 10.6–20.4 months, respectively), as compared with those more than 10 U/mL (median: 42.0 and 9.0 months with 95% CI: 34.4–49.7 and 6.6–11.2 months, respectively). Baseline serum CA-125 levels, but not the CA-125 expression in tissues, were associated with the OS and PFS of HG-SOC patients in the MDACC and JICR groups. However, these values were not independent. Nadir CA-125 levels were not associated with the tumor burden based on second-look surgery (p = 0.09). Patients who achieved a pathologic complete response had longer OS and PFS (median: 73.7 and 20.7 months with 95% CI: 63.7–83.7 and 9.5–31.9 months, respectively) than those with residual tumors (median: 34.6 and 10.6 months with 95% CI: 6.9–62.3 and 4.9–16.3 months, respectively). CONCLUSIONS: The nadir CA-125 level was an independent predictor of OS and PFS in HG-SOC patients. Further prospective studies are required to clinically optimize the chances for a complete clinical response of HG-SOC cases with higher CA-125 levels (>10 U/mL) at the end of primary treatment

Highly curved reflective W-shape and J-shape photonic hook induced by light interaction with partially coated microfluidic channels

Photonic hook (PH) is a new type of artificial self-bending beam focused by a dielectric particle-lens with a curved waist smaller than the wavelength, which has the potential to revolutionize mesoscale photonics in many applications, e.g., optical trapping, signal switching, imaging, etc. In this paper, we discover a new mechanism that the highly curved PHs can be realised by the light interaction with the fully or partially metal-coated microchannels. The generated W-shaped and J-shaped PHs have bending angles exceeding 80-degree. Compared to other PH setups, the proposed design has a larger range to flexibly control the bending angle through the coating process and can be easily integrated with the established microfluidic systems.Comment: 10 pages, 5 figure

Ultrasound-guided percutaneous implantation of rabbit VX2 carcinoma, using a coaxial technique and gelfoam pellet injection combination to establish a rabbit liver tumor model

PURPOSEWe aimed to investigate the safety and tumor seeding rate of a coaxial implantation technique combined with injection of a gelfoam pellet in establishing a VX2 liver tumor model in rabbits.METHODSA VX2 liver tumor model was established in 60 male New Zealand white rabbits, which were randomly divided into 3 groups (20 in each group) based on implantation technique (all performed under ultrasound guidance): group A, single needle only; group B, single needle with injection of a gelfoam pellet; or group C, coaxial technique with injection of a gelfoam pellet. The rates of liver tumor formation and tumor seeding to extrahepatic tissues were compared 2 weeks after implantation. Data were also collected regarding procedure time, number of punctures, occurrence of complications, and mortality rate.RESULTSA VX2 liver tumor model was established in all 60 rabbits (100%, 60/60). Ectopic implantation rate was 70% (14/20) in group A, 35% (7/20) in group B, and 5% (1/20) in group C, with significant difference among the groups (p < 0.001). Post hoc analysis showed significant difference between group A and group C (p < 0.001). However, there were no significant differences between group B and group A or group C (p = 0.027, p = 0.048, respectively). There were no significant differences among the groups in terms of procedure time (p = 0.405) or number of punctures (p = 0.612). No complications or deaths occurred.CONCLUSIONA coaxial technique with injection of a gelfoam pellet is an effective and safe method for VX2 liver tumor implantation in rabbits, and this technique can reduce the risk of tumor seeding to the abdominal wall and omentum

Design of experiment (DoE)-driven in vitro and in vivo uptake studies of exosomes for pancreatic cancer delivery enabled by copper-free click chemistry-based labelling

Exosomes (Exo)-based therapy holds promise for treatment of lethal pancreatic cancer (PC). Limited understanding of key factors affecting Exo uptake in PC cells restricts better design of Exo-based therapy. This work aims to study the uptake properties of different Exo by PC cells. Exo from pancreatic carcinoma, melanoma and non-cancer cell lines were isolated and characterised for yield, size, morphology and exosomal marker expression. Isolated Exo were fluorescently labelled using a novel in-house developed method based on copper-free click chemistry to enable intracellular tracking and uptake quantification in cells. Important factors influencing Exo uptake were initially predicted by Design of Experiments (DoE) approach to facilitate subsequent actual experimental investigations. Uptake of all Exo types by PC cells (PANC-1) showed time- and dose-dependence as predicted by the DoE model. PANC-1 cell-derived exosomes (PANC-1 Exo) showed significantly higher uptake in PANC-1 cells than that of other Exo types at the longest incubation time and highest Exo dose. In vivo biodistribution studies in subcutaneous tumour-bearing mice similarly showed favoured accumulation of PANC-1 Exo in self-tissue (i.e. PANC-1 tumour mass) over the more vascularised melanoma (B16-F10) tumours, suggesting intrinsic tropism of PC-derived Exo for their parent cells. This study provides a simple, universal and reliable surface modification approach via click chemistry for in vitro and in vivo exosome uptake studies and can serve as a basis for a rationalised design approach for pre-clinical Exo cancer therapies

Membrane radiolabelling of exosomes for comparative biodistribution analysis in immunocompetent and immunodeficient mice – a novel and universal approach

Extracellular vesicles, in particular exosomes, have recently gained interest as novel drug delivery vectors due to their biological origin and inherent intercellular biomolecule delivery capability. An in-depth knowledge of their in vivo biodistribution is therefore essential. This work aimed to develop a novel, reliable and universal method to radiolabel exosomes to study their in vivo biodistribution. Methods: Melanoma (B16F10) cells were cultured in bioreactor flasks to increase exosome yield. B16F10-derived exosomes (ExoB₁₆) were isolated using ultracentrfugation onto a single sucrose cushion, and were characterised for size, yield, purity, exosomal markers and morphology using Nanoparticle Tracking Analysis (NTA), protein measurements, flow cytometry and electron microscopy. ExoB₁₆ were radiolabelled using 2 different approaches – intraluminal labelling (entrapment of ¹¹¹Indium via tropolone shuttling); and membrane labelling (chelation of ¹¹¹Indium via covalently attached bifunctional chelator DTPA-anhydride). Labelling efficiency and stability was assessed using gel filtration and thin layer chromatography. Melanoma-bearing immunocompetent (C57BL/6) and immunodeficient (NSG) mice were injected intravenously with radiolabelled ExoB₁₆ (1x10¹¹ particles/mouse) followed by metabolic cages study, whole body SPECT-CT imaging and ex vivo gamma counting at 1, 4 and 24 h post-injection. Results: Membrane-labelled ExoB₁₆ showed superior radiolabelling efficiency and radiochemical stability (19.2 ± 4.53 % and 80.4 ± 1.6 % respectively) compared to the intraluminal-labelled exosomes (4.73 ± 0.39 % and 14.21 ± 2.76 % respectively). Using the membrane-labelling approach, the in vivo biodistribution of ExoB₁₆ in melanoma-bearing C57Bl/6 mice was carried out, and was found to accumulate primarily in the liver and spleen (~56% and ~38% ID/gT respectively), followed by the kidneys (~3% ID/gT). ExoB₁₆ showed minimal tumour i.e. self-tissue accumulation (~0.7% ID/gT). The membrane-labelling approach was also used to study ExoB₁₆ biodistribution in melanoma-bearing immunocompromised (NSG) mice, to compare with that in the immunocompetent C57Bl/6 mice. Similar biodistribution profile was observed in both C57BL/6 and NSG mice, where prominent accumulation was seen in liver and spleen, apart from the significantly lower tumour accumulation observed in the NSG mice (~0.3% ID/gT). Conclusion: Membrane radiolabelling of exosomes is a reliable approach that allows for accurate live imaging and quantitative biodistribution studies to be performed on potentially all exosome types without engineering parent cells

TESS delivers its first Earth-sized planet and a warm sub-Neptune

The future of exoplanet science is bright, as TESS once again demonstrates with the discovery of its longest-period confirmed planet to date. We hereby present HD 21749b (TOI 186.01), a sub-Neptune in a 36-day orbit around a bright (V = 8.1) nearby (16 pc) K4.5 dwarf. TESS measures HD21749b to be 2.61$^{+0.17}_{-0.16}$ $R_{\oplus}$, and combined archival and follow-up precision radial velocity data put the mass of the planet at $22.7^{+2.2}_{-1.9}$ $M_{\oplus}$. HD 21749b contributes to the TESS Level 1 Science Requirement of providing 50 transiting planets smaller than 4 $R_{\oplus}$ with measured masses. Furthermore, we report the discovery of HD 21749c (TOI 186.02), the first Earth-sized ($R_p = 0.892^{+0.064}_{-0.058} R_{\oplus}$) planet from TESS. The HD21749 system is a prime target for comparative studies of planetary composition and architecture in multi-planet systems.Comment: Published in ApJ Letters; 5 figures, 1 tabl

TESS spots a mini-neptune interior to a hot saturn in the TOI-2000 system

Hot jupiters (P 60 $\mathrm{M}_\oplus$) are almost always found alone around their stars, but four out of hundreds known have inner companion planets. These rare companions allow us to constrain the hot jupiter's formation history by ruling out high-eccentricity tidal migration. Less is known about inner companions to hot Saturn-mass planets. We report here the discovery of the TOI-2000 system, which features a hot Saturn-mass planet with a smaller inner companion. The mini-neptune TOI-2000 b ($2.70 \pm 0.15 \,\mathrm{R}_\oplus$, $11.0 \pm 2.4 \,\mathrm{M}_\oplus$) is in a 3.10-day orbit, and the hot saturn TOI-2000 c ($8.14^{+0.31}_{-0.30} \,\mathrm{R}_\oplus$, $81.7^{+4.7}_{-4.6} \,\mathrm{M}_\oplus$) is in a 9.13-day orbit. Both planets transit their host star TOI-2000 (TIC 371188886, V = 10.98, TESS magnitude = 10.36), a metal-rich ([Fe/H] = $0.439^{+0.041}_{-0.043}$) G dwarf 174 pc away. TESS observed the two planets in sectors 9-11 and 36-38, and we followed up with ground-based photometry, spectroscopy, and speckle imaging. Radial velocities from CHIRON, FEROS, and HARPS allowed us to confirm both planets by direct mass measurement. In addition, we demonstrate constraining planetary and stellar parameters with MIST stellar evolutionary tracks through Hamiltonian Monte Carlo under the PyMC framework, achieving higher sampling efficiency and shorter run time compared to traditional Markov chain Monte Carlo. Having the brightest host star in the V band among similar systems, TOI-2000 b and c are superb candidates for atmospheric characterization by the JWST, which can potentially distinguish whether they formed together or TOI-2000 c swept along material during migration to form TOI-2000 b.Comment: v3 adds RV frequency analysis; 25 pages, 11 figures, 14 tables; revision submitted to MNRAS; machine-readable tables available as ancillary files; posterior samples available from Zenodo at https://doi.org/10.5281/zenodo.7683293 and source code at https://doi.org/10.5281/zenodo.798826

From International Schools in Asia to Anglophone World-Class Universities: Student Preparation, Transition, and Development

Thesis advisor: Hans de WitThesis advisor: Gerardo L. BlancoToday’s global knowledge economy has become complex, dynamic, and competitive. In this environment, the talented workforce is increasingly diverse, educated, and mobile. International talents tend to migrate to anglophone countries and contribute to technological innovation, scientific discoveries, and economic growth. The largest international student population in the top destination countries comes from Asia. At the same time, research has shown that Asian international students reported lower satisfaction and higher adjustment challenges due to linguistic and cultural barriers, negatively impacting their learning and living experiences. This dissertation aims to understand and explain the transnational transition process through a subset of the Asian international student population. Thirty-five current university student interviewees are purposefully selected. They are graduates of the “International Baccalaureate Diploma Programme,” a rigorous education pathway program popular in Asia for families to prepare their children for Western higher education. Asian International Baccalaureate (IB) alums, who received education in linguistically and culturally diverse settings, offered more nuanced and complex answers to what traditional literature has indicated about international student transitions and experiences. A Successful International University Transition Model is generated from the grounded theory analysis. This model illustrates the causal and intervening conditions that impact international transitions, with the central tasks of being a university student and becoming an adult. Further, the results are discussed with Bourdieu’s concepts of habitus/practice to explain the heterogeneity in the process amongst the diverse international student population. Lastly, recommendations to stakeholders suggest ways to support globally mobile young adults in their transition and development journey.Thesis (PhD) — Boston College, 2023.Submitted to: Boston College. Lynch School of Education.Discipline: Educational Leadership and Higher Education