Hepatic arterial infusion chemotherapy for hepatocellular carcinoma refractory to transarterial chemoembolization: exploring the influence of prior transarterial chemoembolization and additional transarterial chemoembolization on survival outcomes.

Background: The selection of an efficacious treatment modality for patients with hepatocellular carcinoma (HCC) diagnosed as refractory to transarterial chemoembolization (TACE) presents numerous challenges. In addition to systemic therapies, hepatic arterial infusion chemotherapy (HAIC) may serve as an alternative option. However, it is imperative to identify patients who are appropriate candidates for HAIC to confer a survival benefit. Our study aimed to evaluate the impact of the number of TACE sessions prior to HAIC treatment and the addition of TACE during HAIC on the survival of HCC patient's refractory to TACE. Methods: This retrospective study included 82 patients with HCC refractory to TACE (mean age 60.5 years, 75 males). Survival analysis was conducted using the Kaplan-Meier method, with comparison between two groups via the log-rank test; the Cox regression model was utilized to identify factors influencing survival. Results: The overall response rate (ORR) was observed to be 29.3%, with a disease control rate (DCR) of 56.1%. Patients receiving more than four TACE sessions prior to HAIC exhibited a significantly poorer survival prognosis compared to those receiving fewer than four TACE sessions, with a hazard ratio (HR) of 0.151 (P=0.02). The median overall survival (OS) was markedly different, being 3.4 (range, 0.5-13.6) months for the former group and 14 (range, 8.5-19.5) months for the latter (P=0.01). Furthermore, patients undergoing additional TACE while receiving HAIC treatment demonstrated improved survival outcomes compared to those who did not, with an HR of 0.491 (P=0.02); the respective OS for these groups was 14 (range, 3.6-14.4) and 6.7 (range, 2.8-11) months (P=0.02). Conclusions: HAIC can be a suitable alternative treatment for HCC patient's refractory to TACE. For those with a history of more than 4 TACE sessions, other alternative treatments should be considered. The addition of TACE during HAIC treatment may extend patient OS time, provided it is balanced with maintaining safe liver function.

Transarterial chemoembolization for omental vein tumor thrombosis in hepatocellular carcinoma: a case report.

Background: In hepatocellular carcinoma (HCC) patients, recognizing major vascular invasions such as portal vein tumor thrombosis (PVTT) and hepatic vein tumor thrombosis (HVTT) is crucial for disease staging. Less documented is the invasion of other vessels. We report a case of omental vein tumor thrombosis (OVTT) in an HCC patient treated with transarterial chemoembolization (TACE). Case Description: A 74-year-old male patient with hepatitis B infection was diagnosed with HCC in segment 8 five years ago and treated with radiofrequency ablation (RFA). The tumor recurred at the ablation site, measuring 25 mm × 18 mm, invading the portal vein branch of the posterior segment and a omental vein, showing tumor thrombosis. The patient received TACE targeting branches from the right hepatic artery and omental artery. After two TACE sessions, the tumor and thrombosis completely responded, and tumor markers returned to normal. Conclusions: This case report highlights the uncommon presentation of OVTT alongside PVTT in advanced HCC, emphasizing the need for vigilance in diagnosing atypical disease progressions in HCC and a possible treatment efficacy of TACE.

Arterial-Portal Venous Shunt after Drug-Eluting Bead Transarterial Chemoembolization for Hepatocellular Carcinoma Patients: Risk factors and Impact on Patient Survival.

INTRODUCTION: The effectiveness of transarterial chemoembolization (TACE) in treating hepatocellular carcinoma (HCC) has been well established. The differential impacts of drug-eluting bead TACE (DEB-TACE) as opposed to conventional TACE (cTACE) on vascular changes, such as arterial-portal venous shunts (APS), have been recognized. However, their subsequent effects on treatment outcomes have not been fully explored. This study aims to identify risk factors associated with the occurrence of APS in HCC patients treated with DEB-TACE and to evaluate its impact on patient survival. METHODS: A retrospective analysis was conducted from January 2012 to December 2018 including 74 HCC patients receiving DEB-TACE as initial treatment and a 1:1 conventional cTACE. Kaplan-Meier analysis estimated overall survival (OS) and progression-free survival (PFS). Logistic regression identified significant risk factors for APS occurrence after DEB-TACE. RESULTS: APS incidence was significantly higher after DEB-TACE than cTACE (46.0% vs. 16.2%, p < 0.001). No significant difference in median OS between APS and non-APS groups after DEB-TACE: 50 months (24.6-75.4) vs 26.9 months (19.5-43.2), p = 0.111; median PFS was 15.6 months (4.1-27.1) and 9.5 months (6.8-12.1) for the two groups, respectively, p = 0.065. Risk factors for APS occurrence after DEB-TACE were more than two feeding arteries (OR: 7.25, 95% CI: 1.82-28.95, p = 0.005) and non-selective embolization (OR: 8.02, 95% CI: 2.30-27.95, p = 0.001). CONCLUSION: APS occurrence was higher in DEB-TACE-treated HCC patients, but it did not significantly affect overall survival and progression free survival. More than two feeding arteries and non-selective embolization were significant risk factors for APS occurrence after DEB-TACE.

Percutaneous transhepatic bilioenteric neoanastomosis: A novel approach for managing bile duct injuries following choledochal cyst resection in patients with anatomical variations of the biliary tree: A case study.

Bile duct injuries are rare complications of hepatobiliary pancreatic surgery, leading to severe complications if not timely diagnosed and treated, with surgery traditionally being the primary treatment option. However, percutaneous transhepatic or endoscopic interventions have recently gained widespread use. We present a case study of a patient with variant biliary anatomy, who suffered biliary tract injury postcholedochal cyst resection and Roux-en-Y hepaticojejunostomy; successfully treated with percutaneous transhepatic bilioenteric neoanastomosis, guided by ultrasound and digital subtraction angiography (DSA).

Usefulness of tumor perfusion on cone-beam CT after hepatic arterial infusion port implantation for evaluating tumor response to hepatic arterial infusion chemotherapy in hepatocellular carcinoma treatment.

PURPOSE: To compare tumor perfusion on cone-beam computed tomography (CBCT) after hepatic artery infusion port implantation with the tumor response to hepatic arterial infusion chemotherapy (HAIC) in patients with hepatocellular carcinoma (HCC). METHODS: This retrospective study was conducted in patients with advanced HCC treated with HAIC from 2015 to 2020. We performed CBCT with contrast injection via a port on the day following implantation. We classified tumor perfusion on CBCT into three groups: hyperperfusion, isoperfusion, and hypoperfusion. We also evaluated tumor response to HAIC on follow-up images using RECIST 1.1 and compared it with tumor perfusion on CBCT. RESULTS: This study included 206 tumors in 193 patients (mean: 60.5 years) with HCC. There were 100 hyperperfusion tumors (48.5%), 92 isoperfusion tumors (44.7%), and 14 hypoperfusion tumors (6.8%). The tumor response to HAIC included 10 tumors with a complete response (CR) (4.9%), 66 tumors with a partial response (32%), 60 tumors with stable disease (29.1%), and 70 tumors with progressive disease (34%). Hyperperfusion tumors had a 65% objective response rate (ORR) and a 92% disease control rate (DCR). Isoperfusion tumors had a 12% ORR and a 46.8% DCR, while hypoperfusion tumors had a 0% ORR and a 7.1% DCR. A CR was shown only in hyperperfusion tumors. The ORR and DCR of the three groups were different, with statistical significance (P < 0.001). CONCLUSION: Hyperperfusion tumors on CBCT showed a better tumor response to HAIC, with a 65% ORR in patients with HCC. Tumor perfusion on CBCT after implantation of the hepatic arterial infusion port was associated with the tumor response to HAIC.

Finnish parliament ASR corpus: Analysis, benchmarks and statistics.

Public sources like parliament meeting recordings and transcripts provide ever-growing material for the training and evaluation of automatic speech recognition (ASR) systems. In this paper, we publish and analyse the Finnish Parliament ASR Corpus, the most extensive publicly available collection of manually transcribed speech data for Finnish with over 3000 h of speech and 449 speakers for which it provides rich demographic metadata. This corpus builds on earlier initial work, and as a result the corpus has a natural split into two training subsets from two periods of time. Similarly, there are two official, corrected test sets covering different times, setting an ASR task with longitudinal distribution-shift characteristics. An official development set is also provided. We developed a complete Kaldi-based data preparation pipeline and ASR recipes for hidden Markov models (HMM), hybrid deep neural networks (HMM-DNN), and attention-based encoder-decoders (AED). For HMM-DNN systems, we provide results with time-delay neural networks (TDNN) as well as state-of-the-art wav2vec 2.0 pretrained acoustic models. We set benchmarks on the official test sets and multiple other recently used test sets. Both temporal corpus subsets are already large, and we observe that beyond their scale, HMM-TDNN ASR performance on the official test sets has reached a plateau. In contrast, other domains and larger wav2vec 2.0 models benefit from added data. The HMM-DNN and AED approaches are compared in a carefully matched equal data setting, with the HMM-DNN system consistently performing better. Finally, the variation of the ASR accuracy is compared between the speaker categories available in the parliament metadata to detect potential biases based on factors such as gender, age, and education.

Three-dimensional flagella structures from animals' closest unicellular relatives, the Choanoflagellates.

In most eukaryotic organisms, cilia and flagella perform a variety of life-sustaining roles related to environmental sensing and motility. Cryo-electron microscopy has provided considerable insight into the morphology and function of flagellar structures, but studies have been limited to less than a dozen of the millions of known eukaryotic species. Ultrastructural information is particularly lacking for unicellular organisms in the Opisthokonta clade, leaving a sizeable gap in our understanding of flagella evolution between unicellular species and multicellular metazoans (animals). Choanoflagellates are important aquatic heterotrophs, uniquely positioned within the opisthokonts as the metazoans' closest living unicellular relatives. We performed cryo-focused ion beam milling and cryo-electron tomography on flagella from the choanoflagellate species Salpingoeca rosetta. We show that the axonemal dyneins, radial spokes, and central pair complex in S. rosetta more closely resemble metazoan structures than those of unicellular organisms from other suprakingdoms. In addition, we describe unique features of S. rosetta flagella, including microtubule holes, microtubule inner proteins, and the flagellar vane: a fine, net-like extension that has been notoriously difficult to visualize using other methods. Furthermore, we report barb-like structures of unknown function on the extracellular surface of the flagellar membrane. Together, our findings provide new insights into choanoflagellate biology and flagella evolution between unicellular and multicellular opisthokonts.

Percutaneous Transhepatic Cholecystolithotomy by Holmium Laser for Non-high-Risk Patients with Symptomatic Gallbladder Stones.

Background: The development of gallstones, also known as cholelithiasis, is one of the most common diseases associated with the gastrointestinal tract. In developing countries 10% to 15% of men and >25% of women experience gallstones. Objective: The aim of the study was to evaluate the outcomes following percutaneous transhepatic cholecystolithotomy by holmium laser in non-high-risk patients with symptomatic gallbladder stones. Methods: This was an intervention study without control and with longitudinal follow-up. Subjects included patients who had only gallbladder stones, a normal gallbladder contractility index, and required a conservative treatment. Results: The study included 44 patients (20 men, 24 women), with a mean age of 41.5 ± 13.4 years. The success rate was 97.7%, and only 1 of 44 patients required follow-up laparoscopic cholecystectomy. Gallstones were successfully removed from 43 of 44 patients (97.7%). The complication rate was 13.6% (6/44 patients), and only minor complications were reported for 5 of the 6 patients with complications. In 34 of 43 patients, follow-up examinations were performed after 1 and 6 months. The gallstone recurrence rate at six-month follow-up was 11.8%, and a collapsed gallbladder was detected in 1 of 34 patients, with the remaining 33 patients retaining normal gallbladder contractility indices (>40%). Conclusion: Percutaneous transhepatic cholecystolithotomy by holmium laser has a high gallstone removal rate (97.7%); however, recurrence remains a major problem. The complication rate was about 13.6%, most of which were minor complications. Cases associated with treatment failure or serious complications should be detected and treated promptly.

Percutaneous embolization of hepatic lymphorrhea post-hepatectomy.

Abdominal effusion due to hepatic lymphorrhea post-hepatectomy is an extremely rare and complex complication in clinical practice. No standard treatment method has been established for this condition to date. We report a case of complicated intra-abdominal lymphatic leakage in a patient following hepatectomy to treat hepatocellular carcinoma. The patient underwent percutaneous embolization of the hilar hepatic lymphatic system, combined with intensive medical treatment. Percutaneous embolization represents a safe and effective method that should be considered as a first-line treatment for this complication.

Effects of autophagy inhibition by chloroquine on hepatic stellate cell activation in CCl4-induced acute liver injury mouse model.

BACKGROUND AND AIM: Hepatic stellate cells (HSCs) activation, a critical event in liver fibrosis, has been recently shown to be related to autophagy. Determine whether chloroquine (CQ) could affect (i) the activation of HSC in vivo and (ii) the hepatic damage in a mice acute liver injury model. METHODS: The acute liver injury was induced in BALB/c mice by carbon tetrachloride (CCl4 group); 24 h before and after CCl4 administration animals were treated by CQ (CCl4  + CQ group). As control, mice treated by olive oil were considered. After 48 h from CCl4 /olive oil administration, blood samples, liver tissues, and HSCs were harvested for analysis. RESULTS: In vivo, CQ attenuates CCl4 -induced acute liver damage as evidenced by (i) the reduction of liver enlargement, (ii) the reduction of liver swelling and necrosis also supported by a certain decrease of circulating transaminases level, and (iii) the reduction of liver fibrosis evaluated by collagen deposition and α-sma protein expression. In HSCs isolated from CQ treated group, we observed the inhibition of autophagy proved by the increase in p62 protein and the decrease of lc3 protein. In addition, CQ reduced the expression of the HSCs activation markers α-sma/collagen-I and down-regulated the expression of the proliferative marker ki67. CONCLUSION: The autophagy attenuation exerted by CQ together with the reduction of the expression of the proliferation marker in HSCs can lessen the acute liver damage potentially opening the way to novel therapeutic approaches for hepatic fibrosis.

Structural organization of the C1b projection within the ciliary central apparatus.

Motile cilia have a '9+2' structure containing nine doublet microtubules and a central apparatus (CA) composed of two singlet microtubules with associated projections. The CA plays crucial roles in regulating ciliary motility. Defects in CA assembly or function usually result in motility-impaired or paralyzed cilia, which in humans causes disease. Despite their importance, the protein composition and functions of most CA projections remain largely unknown. Here, we combined genetic, proteomic and cryo-electron tomographic approaches to compare the CA of wild-type Chlamydomonas reinhardtii with those of three CA mutants. Our results show that two proteins, FAP42 and FAP246, are localized to the L-shaped C1b projection of the CA, where they interact with the candidate CA protein FAP413. FAP42 is a large protein that forms the peripheral 'beam' of the C1b projection, and the FAP246-FAP413 subcomplex serves as the 'bracket' between the beam (FAP42) and the C1b 'pillar' that attaches the projection to the C1 microtubule. The FAP246-FAP413-FAP42 complex is essential for stable assembly of the C1b, C1f and C2b projections, and loss of these proteins leads to ciliary motility defects.

Docetaxel-loaded PLGA nanoparticles to increase pharmacological sensitivity in MDA-MB-231 and MCF-7 breast cancer cells.

This study aimed to develop docetaxel (DTX) loaded poly(lactic-coglycolic acid) (PLGA) nanoparticles (DTX-NPs) and to evaluate the different pharmacological sensitivity of NPs to MCF-7 and MDA-MB-231 breast cancer cells. NPs containing DTX or coumarin-6 were prepared by the nanoprecipitation method using PLGA as a polymer and d-α-tocopherol polyethylene glycol 1000 succinate (TPGS) as a surfactant. The physicochemical properties of NPs were characterized. In vitro anticancer effect and cellular uptake were evaluated in breast cancer cells. The particle size and zeta potential of the DTX-NPs were 160.5 ± 3.0 nm and -26.7 ± 0.46 mV, respectively. The encapsulation efficiency and drug loading were 81.3 ± 1.85% and 10.6 ± 0.24%, respectively. The in vitro release of DTX from the DTX-NPs was sustained at pH 7.4 containing 0.5% Tween 80. The viability of MDA-MB-231 and MCF-7 cells with DTX-NPs was 37.5 ± 0.5% and 30.3 ± 1.13%, respectively. The IC50 values of DTX-NPs were 3.92- and 6.75-fold lower than that of DTX for MDA-MB-231 cells and MCF-7 cells, respectively. The cellular uptake of coumarin-6-loaded PLGA-NPs in MCF-7 cells was significantly higher than that in MDA-MB-231 cells. The pharmacological sensitivity in breast cancer cells was higher on MCF-7 cells than on MDA-MB-231 cells. In conclusion, we successfully developed DTX-NPs that showed a great potential for the controlled release of DTX. DTX-NPs are an effective formulation for improving anticancer effect in breast cancer cells.

Structural organization of the intermediate and light chain complex of Chlamydomonas ciliary I1 dynein.

Axonemal I1 dynein (dynein f) is the largest inner dynein arm in cilia and a key regulator of ciliary beating. It consists of two dynein heavy chains, and an intermediate chain/light chain (ICLC) complex. However, the structural organization of the nine ICLC subunits remains largely unknown. Here, we used biochemical and genetic approaches, and cryo-electron tomography imaging in Chlamydomonas to dissect the molecular architecture of the I1 dynein ICLC complex. Using a strain expressing SNAP-tagged IC140, tomography revealed the location of the IC140 N-terminus at the proximal apex of the ICLC structure. Mass spectrometry of a tctex2b mutant showed that TCTEX2B dynein light chain is required for the stable assembly of TCTEX1 and inner dynein arm interacting proteins IC97 and FAP120. The structural defects observed in tctex2b located these 4 subunits in the center and bottom regions of the ICLC structure, which overlaps with the location of the IC138 regulatory subcomplex, which contains IC138, IC97, FAP120, and LC7b. These results reveal the three-dimensional organization of the native ICLC complex and indicate potential protein-protein interactions that are involved in the pathway by which I1 regulates ciliary motility.

Docetaxel-loaded PLGA nanoparticles to increase pharmacological sensitivity in MDA-MB-231 and MCF-7 breast cancer cells

This study aimed to develop docetaxel (DTX) loaded poly(lactic-coglycolic acid) (PLGA) nanoparticles (DTX-NPs) and to evaluate the different pharmacological sensitivity of NPs to MCF-7 and MDA-MB-231 breast cancer cells. NPs containing DTX or coumarin-6 were prepared by the nanoprecipitation method using PLGA as a polymer and d-α-tocopherol polyethylene glycol 1000 succinate (TPGS) as a surfactant. The physicochemical properties of NPs were characterized. In vitro anticancer effect and cellular uptake were evaluated in breast cancer cells. The particle size and zeta potential of the DTX-NPs were 160.5 ± 3.0 nm and –26.7 ± 0.46 mV, respectively. The encapsulation efficiency and drug loading were 81.3 ± 1.85% and 10.6 ± 0.24%, respectively. The In vitro release of DTX from the DTX-NPs was sustained at pH 7.4 containing 0.5% Tween 80. The viability of MDA-MB-231 and MCF-7 cells with DTX-NPs was 37.5 ± 0.5% and 30.3 ± 1.13%, respectively. The IC 50 values of DTX-NPs were 3.92- and 6.75-fold lower than that of DTX for MDA-MB-231 cells and MCF-7 cells, respectively. The cellular uptake of coumarin-6-loaded PLGA-NPs in MCF-7 cells was significantly higher than that in MDA-MB-231 cells. The pharmacological sensitivity in breast cancer cells was higher on MCF-7 cells than on MDA-MB-231 cells. In conclusion, we successfully developed DTX-NPs that showed a great potential for the controlled release of DTX. DTX-NPs are an effective formulation for improving anticancer effect in breast cancer cells.

Docetaxel-loaded PLGA nanoparticles to increase pharmacological sensitivity in MDA-MB-231 and MCF-7 breast cancer cells

This study aimed to develop docetaxel (DTX) loaded poly(lactic-coglycolic acid) (PLGA) nanoparticles (DTX-NPs) and to evaluate the different pharmacological sensitivity of NPs to MCF-7 and MDA-MB-231 breast cancer cells. NPs containing DTX or coumarin-6 were prepared by the nanoprecipitation method using PLGA as a polymer and d-α-tocopherol polyethylene glycol 1000 succinate (TPGS) as a surfactant. The physicochemical properties of NPs were characterized. In vitro anticancer effect and cellular uptake were evaluated in breast cancer cells. The particle size and zeta potential of the DTX-NPs were 160.5 ± 3.0 nm and –26.7 ± 0.46 mV, respectively. The encapsulation efficiency and drug loading were 81.3 ± 1.85% and 10.6 ± 0.24%, respectively. The In vitro release of DTX from the DTX-NPs was sustained at pH 7.4 containing 0.5% Tween 80. The viability of MDA-MB-231 and MCF-7 cells with DTX-NPs was 37.5 ± 0.5% and 30.3 ± 1.13%, respectively. The IC 50 values of DTX-NPs were 3.92- and 6.75-fold lower than that of DTX for MDA-MB-231 cells and MCF-7 cells, respectively. The cellular uptake of coumarin-6-loaded PLGA-NPs in MCF-7 cells was significantly higher than that in MDA-MB-231 cells. The pharmacological sensitivity in breast cancer cells was higher on MCF-7 cells than on MDA-MB-231 cells. In conclusion, we successfully developed DTX-NPs that showed a great potential for the controlled release of DTX. DTX-NPs are an effective formulation for improving anticancer effect in breast cancer cells.

Optimization of the isolation procedure and culturing conditions for hepatic stellate cells obtained from mouse.

Liver fibrosis (LF) mortality rate is approximately 2 million per year. Irrespective of the etiology of LF, a key element in its development is the transition of hepatic stellate cells (HSCs) from a quiescent phenotype to a myofibroblast-like cell with the production of fibrotic proteins. It is necessary to define optimal isolation and culturing conditions for good HSCs yield and proper phenotype preservation for studying the activation of HSCs in vitro. In the present study, the optimal conditions of HSC isolation and culture were examined to maintain the HSC's undifferentiated phenotype. HSCs were isolated from Balb/c mice liver using Nycodenz, 8, 9.6, and 11%. The efficiency of the isolation procedure was evaluated by cell counting and purity determination by flow cytometry. Quiescent HSCs were cultured in test media supplemented with different combinations of fetal bovine serum (FBS), glutamine (GLN), vitamin A (vitA), insulin, and glucose. The cells were assessed at days 3 and 7 of culture by evaluating the morphology, proliferation using cell counting kit-8, lipid storage using Oil Red O (ORO) staining, expression of a-smooth muscle actin, collagen I, and lecithin-retinol acyltransferase by qRT-PCR and immunocytochemistry (ICC). The results showed that Nycodenz, at 9.6%, yielded the best purity and quantity of HSCs. Maintenance of HSC undifferentiated phenotype was achieved optimizing culturing conditions (serum-free Dulbecco's Modified Eagle's Medium (DMEM) supplemented with glucose (100 mg/dl), GLN (0.5 mM), vitA (100 µM), and insulin (50 ng/ml)) with a certain degree of proliferation allowing their perpetuation in culture. In conclusion, we have defined optimal conditions for HSCs isolation and culture.

Adipose-Derived Stem Cells Can Replace Fibroblasts as Cell Control for Anti-Tumor Screening Assay.

Anti-tumor activity screening is a typical process used in anti-tumor drug discovery. The ideal anti-tumor drug candidates are extracts or compounds that can inhibit the proliferation of cancer cells via apoptosis, while exerting minimal effects on normal somatic cells. For a long time, fibroblasts were used as normal cells for all anti-tumor screening assays. However, the fibroblasts exhibited several limitations as cell controls for anti-tumor screening. This study aimed to compare the usage of dermal fibroblasts (DFs) and adipose-derived stem cells (ADSCs) as normal cell controls in anti-tumor screening protocols. The DFs and ADSCs were prepared per the published protocols. The IC50 values of doxorubicin on hepatocellular carcinoma cells HepG2, breast cancer cells MCF-7, DFs and ADSCs were determined via the Alamar blue assay. The side effect indexes (SEIs) were calculated as the ratio of IC50 values of drugs on cancer cells and IC50 values of drugs on DFs, and on ADSCs. The stability of the anti-tumor assay was investigated when carried out on DFs and ADSCs from different passages. The results showed that the IC50 values, as well as SEI values, were not significantly different between using DFs or ADSCs as normal cell controls when DFs and ADSCs were at passage 3. However, for DFs at passage 6 to 12, the IC50 values of doxorubicin were significantly different between DFs and ADSCs. The IC50 values of doxorubicin on DFs were strongly reduced due to the senescence of DFs, while the values were more constant in ADSCs. The SEI values of doxorubicin on DFs, compared to HepG2 and MCF-7 cells, were also changed during passage 3 to 12 of the DFs. However, these values were only slightly changed for ADSCs from the 3rd to 12th passages. ADSCs can replace DFs as a normal cell control for anti-tumor activity screening.

Hopea odorata Extract Can Efficiently Kill Breast Cancer Cells and Cancer Stem-Like Cells in Three-Dimensional Culture More Than in Monolayer Cell Culture.

INTRODUCTION: The breast cancer cells with CD44+CD24- phenotype are known to play an important role in tumorigenesis, drug resistance, and cancer recurrence. Breast cancer cells with CD44+CD24- phenotype are cultured in three-dimensional (3D) stereotype showing the recapitulation of tumors in vivo such as cell differentiation, heterogeneity, and microenvironment. Using this 3D model in anti-cancer compound research results in a more accurate reflection than conventional monolayer cell culture. This study aimed to identify the antitumor activity of Hopea odorata methanol extract (HO-MeOH-E) on breast cancer cells and cancer stem-like cells in both models of three-dimensional culture (3D) and monolayer cell culture (2D). METHODS: HO-MeOH-E was produced from Hopea odorata plant. The VN9 breast cancer cells (VN9) were collected and expanded from the previous study. The breast cancer stem-like cells (VN9CSC) were sorted from the VN9 based on phenotype CD44+CD24-. Both VN9 and VN9CSC were used to culture in monolayer culture (2D) and organoids (3D) before they were used to treat with HO-MeOH-E. Two other anticancer drugs, doxorubicin and tirapazamine, were used as references. The antitumor activities of extracts and drugs were determined via two assays: antiproliferation using the Alamar blue assay and cell cycle assay. RESULTS: The results showed that HO-MeOH-E was sensitive to both VN9 and VN9CSC in 3D more than 2D culture (IC50 on 3D organoids 144.8 ± 2.172 µg/mL and on 2D 340.2 ± 17.01 µg/mL for VN9CSC (p < 0.001); IC50 on 3D organoids 2055 ± 82.2 µg/mL and on 2D 430.6 ± 8.612 µg/mL for VN9 (p < 0.0001), respectively). HO-MeOH-E inhibits VN9CSC proliferation by blocking S phase and increasing the populations of apoptotic cells; this is consensus to the effect of tirapazamine (TPZ) which is used in hypoxia-activated chemotherapy. CONCLUSION: Taken these results, HO-MeOH-E has the potential effect in hypoxia-activated chemotherapy specifically on breast cancer stem-like cells with CD44+CD24- phenotype.

Structural organization of the C1a-e-c supercomplex within the ciliary central apparatus.

Nearly all motile cilia contain a central apparatus (CA) composed of two connected singlet microtubules with attached projections that play crucial roles in regulating ciliary motility. Defects in CA assembly usually result in motility-impaired or paralyzed cilia, which in humans causes disease. Despite their importance, the protein composition and functions of the CA projections are largely unknown. Here, we integrated biochemical and genetic approaches with cryo-electron tomography to compare the CA of wild-type Chlamydomonas with CA mutants. We identified a large (>2 MD) complex, the C1a-e-c supercomplex, that requires the PF16 protein for assembly and contains the CA components FAP76, FAP81, FAP92, and FAP216. We localized these subunits within the supercomplex using nanogold labeling and show that loss of any one of them results in impaired ciliary motility. These data provide insight into the subunit organization and 3D structure of the CA, which is a prerequisite for understanding the molecular mechanisms by which the CA regulates ciliary beating.

Interventional Treatment of Lymphatic Leakage Post Appendectomy: Case Report.

BACKGROUND: Postoperative lymphatic complications are not common, and lymphatic leakage complication post appendectomy (LLCPC) is even rarer. However, the number of this operation is high so LLCPC can occur. CASE REPORT: Here, we report a female patient post appendectomy with severe chylous ascites. This patient underwent six operations. A leakage point at the right iliac-fossa, which was embolized successfully after two sessions, was spotted during intranodal lymphangiography. After 6 months, the ascites were significantly reduced while some lymphatic aneurysms still existed in the lumbar-retroperitoneal region. CONCLUSIONS: Basing the knowledge of this clinical case and literature, we have concluded that lymphatic leakage can be diagnosed and embolized by percutaneous intervention.