A consultation and work-up diagnosis protocol for a multicancer early detection test: a case series study.

The emergence of multicancer early detection (MCED) tests holds promise for improving early cancer detection and public health outcomes. However, positive MCED test results require confirmation through recommended cancer diagnostic imaging modalities. To address these challenges, we have developed a consultation and work-up protocol for definitive diagnostic results post MCED testing, named SPOT-MAS. Developed through circulating tumor DNA (ctDNA) analysis and in line with professional guidelines and advisory board consensus, this protocol standardizes information to aid general practitioners in accessing, interpreting and managing SPOT-MAS results. Clinical effectiveness is demonstrated through a series of identified cancer cases. Our research indicates that the protocol could empower healthcare professionals to confidently interpret circulating tumor DNA test results for 5 common types of cancer, thereby facilitating the clinical integration of MCED tests.

New tests can now screen for multiple types of cancer early, offering hope for better health outcomes. If one of these tests shows a positive result, doctors need to confirm it with imaging tests. We have developed a guide to help doctors understand and confirm these results. This guide could help healthcare professionals interpret results for five common types of cancer, making it easier to use these tests in regular medical practice.

[Management of patients with complex ear deformities]. / Prise en charge des patients présentant des déformations complexes du pavillon de l'oreille.

Complex ear reconstruction requires specialized multidisciplinary care. Most patients present with microtia, often associated with hearing disorders. The management of these disorders is a priority, and reconstruction of the external ear remains optional. Nowadays, auricular reconstruction is based on the subcutaneous implantation of either autologous cartilage or an allogeneic implant. Autologous reconstruction requires highly specialized surgical expertise and involves harvesting rib cartilage but carries a lower risk of exposure compared to allogeneic implants. Both techniques yield good results with a high success rate and have a positive impact on the social functioning and daily life of patients.

La reconstruction complexe du pavillon auriculaire nécessite une prise en charge multidisciplinaire spécialisée. La majorité des patients nécessitant ce geste présentent une microtie, souvent associée à des troubles de l'audition. La prise en charge de ceux-ci est prioritaire et la reconstruction du pavillon reste facultative. Aujourd'hui, la reconstruction du pavillon se base sur l'implantation sous-cutanée d'une maquette de cartilage autologue ou d'un implant allogène. La reconstruction autologue demande une expertise chirurgicale hautement spécialisée et nécessite un prélèvement de cartilage costal mais présente un risque d'exposition inférieur par rapport à l'implant allogène. Les deux techniques permettent d'atteindre de bons résultats avec un taux de réussite élevé et un effet positif sur le fonctionnement social et le quotidien des patients.

Sesquiterpenes from Streptomyces qinglanensis and Their Cytotoxic Activity.

Nine sesquiterpenes, including eight pentalenenes (1-8) and one bolinane derivative (9), were isolated from the culture broth of a marine-derived actinobacterium Streptomyces qinglanensis 213DD-006. Among them, 1, 4, 7, and 9 were new compounds. Their planar structures were determined by spectroscopic methods (HRMS, 1D, and 2D NMR), and the absolute configuration was established by biosynthesis consideration and electronic-circular-dichroism (ECD) calculations. All the isolated compounds were screened for their cytotoxicity against six solid and seven blood cancer cell lines. Compounds 4-6 and 8 showed a moderate activity against all of the tested solid cell lines, with GI50 values ranging from 1.97 to 3.46 µM.

Pyrrole-Containing Alkaloids from a Marine-Derived Actinobacterium Streptomyces zhaozhouensis and Their Antimicrobial and Cytotoxic Activities.

Two new alkaloids, streptopyrroles B and C (1 and 2), were discovered through a chemical investigation of the ethyl acetate (EtOAc) extract from a marine-derived actinomycete, Streptomyces zhaozhouensis, along with four known analogs (3-6). The structures of the new compounds were elucidated by spectroscopic analysis (HR-ESIMS, 1D, and 2D NMR) and a comparison of their experimental data with literature values. The new compounds were evaluated for their antimicrobial activity by standard broth dilution assay, and the tested compounds showed significant activity against Gram-positive bacteria with minimum inhibitory concentration (MIC) values ranging from 0.7 to 2.9 µM, and kanamycin was used as a positive control with MIC values ranging from <0.5 to 4.1 µM. Additionally, 1, 3, and 5 were evaluated for their cytotoxicity against six tumor cell lines by sulforhodamine B (SRB) assay, and these compounds displayed cytotoxic activities against all the tested cell lines, with concentration causing 50% cell growth inhibition (GI50) values ranging from 4.9 to 10.8 µM, while a positive control, adriamycin, showed GI50 values of 0.13-0.17 µM.

Clinical validation of a ctDNA-Based Assay for Multi-Cancer Detection: An Interim Report from a Vietnamese Longitudinal Prospective Cohort Study of 2795 Participants.

The SPOT-MAS assay "Screening for the Presence Of Tumor by Methylation And Size" detects the five most common cancers in Vietnam by evaluating circulating tumor DNA in the blood. Here, we validated its performance in a prospective multi-center clinical trial, K-DETEK. Our analysis of 2795 participants from 14 sites across Vietnam demonstrates its ability to detect cancers in asymptomatic individuals with a positive predictive value of 60%, with 83.3% accuracy in detecting tumor location. We present a case report to support further using SPOT-MAS as a complementary method to achieve early cancer detection and provide the opportunity for early treatment.

New Angucycline Glycosides from a Marine-Derived Bacterium Streptomyces ardesiacus.

Chemical investigation of the ethyl acetate extract from the culture broth of the marine-derived actinobacterium Streptomyces ardesiacus 156VN-095 led to the isolation of three hitherto undescribed angucycline glycosides, including urdamycins W and X (1 and 2) and grincamycin U (9), as well as their seven known congeners. The structures of the new compounds were elucidated by means of spectroscopic methods (HRESIMS, 1D and 2 D NMR) and comparison of their experimental data with literature values. Compounds 1-3 and 9 were evaluated for their anti-Gram-positive bacterial effect and cytotoxicity against six cancer cell lines. Compound 1 displayed significant cytotoxicity against all the tested cell lines with GI50 values of 0.019-0.104 µM. Collectively, these findings highlight the potential of angucycline glycosides as leading structures for the development of new anti-cancer drugs.

Aspersterols A-D, Ergostane-Type Sterols with an Unusual Unsaturated Side Chain from the Deep-Sea-Derived Fungus Aspergillus unguis.

Four previously undescribed ergostane-type sterols, aspersterols A-D (1-4), were isolated from a deep-sea-derived fungus, Aspergillus unguis IV17-109. The structures of the new compounds were determined by extensive analyses of their spectroscopic data, pyridine-induced deshielding effect, Mosher's method, and electronic circular dichroism calculations. The key feature of these sterols is the presence of a rare unsaturated side chain with conjugated double bonds at Δ17 and Δ22. The absolute configuration of C-24 in the side chain was determined by hydrogenation and comparing 13C NMR chemical shifts of the hydrogenated products with literature values. In addition, aspersterol A (1) is the second representative of anthrasteroids with a hydroxy group at the C-2 position. Compound 1 showed cytotoxicity against six cancer cell lines, with GI50 values of 3.4 ± 0.3 to 4.5 ± 0.7 µM, while 2-4 showed anti-inflammatory activity, with IC50 values ranging from 11.6 ± 1.6 to 19.5 ± 1.2 µM.

New Glycosylated Secondary Metabolites from Marine-Derived Bacteria.

Three new glycosylated secondary metabolites, including a new indole alkaloid, pityriacitrin D (1), and two new trehalose lipids (2 and 3), together with three known compounds (4-6) were isolated from two marine-derived bacterial strains, Bacillus siamensis 168CLC-66.1 and Tsukamurella pseudospumae IV19-045. The structures of 1-3 were determined by extensive analysis and comparison of their spectroscopic data with literature values. The absolute configurations of sugar moieties were determined by chemical derivatization followed by LC-MS analysis. Cytotoxicity of 1-3 against six cancer cell lines was evaluated by SRB assay, and 1 showed moderate activity against all the tested cell lines with GI50 values ranging from 8.0 to 10.9 µM.

Nitrogen-Containing Secondary Metabolites from a Deep-Sea Fungus Aspergillus unguis and Their Anti-Inflammatory Activity.

Aspergillus is well-known as the second-largest contributor of fungal natural products. Based on NMR guided isolation, three nitrogen-containing secondary metabolites, including two new compounds, variotin B (1) and coniosulfide E (2), together with a known compound, unguisin A (3), were isolated from the ethyl acetate (EtOAc) extract of the deep-sea fungus Aspergillus unguis IV17-109. The planar structures of 1 and 2 were elucidated by an extensive analysis of their spectroscopic data (HRESIMS, 1D and 2D NMR). The absolute configuration of 2 was determined by comparison of its optical rotation value with those of the synthesized analogs. Compound 2 is a rare, naturally occurring substance with an unusual cysteinol moiety. Furthermore, 1 showed moderate anti-inflammatory activity with an IC50 value of 20.0 µM. These results revealed that Aspergillus unguis could produce structurally diverse nitrogenous secondary metabolites, which can be used for further studies to find anti-inflammatory leads.

The effects of NUDT15 and TPMT variants on mercaptopurine treatment in Vietnamese pediatric acute lymphoblastic leukemia patients.

6-mercaptopurine (6-MP) plays a critical role in the treatment of pediatric acute lymphoblastic leukemia (ALL). NUDT15 and TPMT gene variants have been strongly associated with myelotoxicity caused by using 6-MP. Therefore, the purpose of this study is to investigate the frequency of NUDT15 and TPMT polymorphisms, as well as the impact of NUDT15 variants on the use of 6-MP to treat pediatric ALL in Vietnam. Sanger sequencing was applied to detect NUDT15 and TPMT gene variants in 70 pediatric ALL patients. Duration of drug interruption, level of neutropenia, and 6-MP tolerance dose were recorded. NUDT15 variants were detected from 23 out of 70 (32.9%) patients. Three well-known haplotype variants were identified as NUDT15 *2 (p.V18_V19insGV and p.R139C), *3 (p.R139C), and *6 (p.V18_V19insGV); besides, a novel NUDT15 p.R11Q was not previously reported. The NUDT15 wild-type, heterozygous variant, and homozygous variant genotypes were 67.1%, 30.1%, and 2.8%, respectively. Two TPMT heterozygous polymorphisms were TPMT*3C and *6, accounted for 2.8%. Patients with intermediate and low activity NUDT15 were given the median 6-MP tolerance dose of 55.2 and 37.2 versus 69.5 mg/m2/day of patients with NUDT15 normal activity (p = 0.0001). Patients with homozygous variant diplotype were drastically sensitive to 6-MP, with an average dose intensity of 49.6%, compared to 73.6% and 92.7% of those with heterozygous and wild-type diplotype, respectively (p = 0.0001). Our results suggest that 6-MP dose adjustment should be based on NUDT15 variants in pediatric Vietnamese ALL patients.

Prevalence and Determinants of Vaginal Infection With Human Papillomavirus Among Female University Students in Vietnam.

BACKGROUND/AIM: Cervical cancer is the second most common malignancy among women in Vietnam, but the country is yet to introduce a national human papillomavirus (HPV) vaccine programme targeted at adolescents. We determined HPV prevalence and HPV vaccine knowledge among female university students in Vietnam. PATIENTS AND METHODS: We surveyed and screened 1,491 female university students in Hanoi, Hue, and Ho Chi Minh City for their sexual behaviours, HPV knowledge and low- and high-risk HPV infection. RESULTS: The prevalence of any HPV infection and any high-risk HPV infection were 4.2% (95%CI=3.3%-5.4%) and 3.4% (95%CI=2.5%-4.4%), respectively. Being sexually active [adjusted prevalence ratio (aPR): 6.22; 95%CI=3.4-11.37] and having ever been pregnant (aPR: 4.82; 95%CI=1.93-12.04) were positively associated with high-risk HPV infection. Whilst 60% of participants had heard of HPV vaccine, only 4.6% had received the vaccine. CONCLUSION: The low HPV prevalence found in university students in Vietnam indicates that they can benefit from HPV vaccination, along with a well-designed HPV health promotion programme.

Streptoglycerides E-H, Unsaturated Polyketides from the Marine-Derived Bacterium Streptomyces specialis and Their Anti-Inflammatory Activity.

Four new streptoglycerides E-H (1-4), with a rare 6/5/5/-membered ring system, were isolated from a marine-derived actinomycete Streptomyces specialis. The structures of 1-4 were elucidated by detailed analysis of HRESIMS, 1D and 2D NMR data and ECD spectra as well as comparison of their spectroscopic data with those reported in literature. Compounds 1-4 showed significant anti-inflammatory activity by inhibiting lipopolysaccharide (LPS)-induced nitric oxide (NO) production in Raw 264.7 cells with IC50 values ranging from 3.5 to 10.9 µM. Especially, 2 suppressed mRNA expression levels of iNOS and IL-6 without cytotoxicity.

Antibacterial and Cytotoxic Phenolic Polyketides from Two Marine-Derived Fungal Strains of Aspergillus unguis.

A chemical investigation on the EtOAc extracts from two marine-derived fungal strains of Aspergillus unguis resulted in the isolation of three previously undescribed phenolic polyketides including unguidepside C (1), aspersidone B (3), and agonodepside C (12), and their 14 known congeners. The structures of the new compounds were determined based on detailed analysis and comparison of their spectroscopic data with literature values, as well as Snatzke's method. The new compounds (1, 3, and 12) displayed a significant anti-Gram-positive bacterial activity, with MIC values ranging from 5.3 to 22.1 µM. Additionally, the isolated compounds (1-11 and 13-16) were evaluated for their cytotoxicity against a panel of tumor cell lines. Most of them (except for 9) displayed cytotoxicity against all the tested cell lines, with IC50 values ranging from 2.5 to 46.9 µM.

Prevalence and risk factors for human papillomavirus infection among female sex workers in Hanoi and Ho Chi Minh City, Viet Nam: a cross-sectional study.

Objective: Female sex workers (FSWs) are at high risk of human papillomavirus (HPV) infections and cervical cancer due to their high number of sexual partners. The objectives of this study were to determine the prevalence of HPV and identify risk factors for high-risk HPV infection among FSWs in Hanoi and Ho Chi Minh City (HCMC), Viet Nam. Methods: A cross-sectional study was conducted in Hanoi and HCMC between December 2017 and May 2018. We surveyed and screened 699 FSWs aged 318 years for HPV infection and abnormal cytology. A multivariable modified Cox regression model was used to determine risk factors for high-risk HPV infection. Results: The overall prevalence of any HPV, high-risk HPV and HPV-16/18 infection in the 699 FSWs was 26.3%, 17.6% and 4.0%, respectively, and were similar in both cities. Multiple infections were identified in 127 participants (69.0%). HPV-52 was the most prevalent (7%), followed by HPV-58 (6%). Abnormal cytology was detected in 91 participants (13.0%). FSWs who are divorced (adjusted prevalence ratio [aPR]: 1.96, 95% confidence interval [CI]: 1.01-3.81), widowed (aPR: 3.26, 95% CI: 1.49-7.12) or living alone (aPR: 1.85, 95% CI: 1.01-3.39) were associated with a higher prevalence of high-risk HPV infection. Discussion: Almost one in five FSWs in Viet Nam are infected with high-risk HPV. This highlights the importance of prevention strategies such as HPV vaccination and screening in this high-risk group.

Anal human papillomavirus prevalence and risk factors among men who have sex with men in Vietnam.

OBJECTIVES: Men who have sex with men (MSM) are at risk of human papillomavirus (HPV)-related cancers, while published data are scarce. This study determined HPV prevalence and risk factors in MSM in Vietnam to inform HPV prevention strategies in this key population. METHODS: A cross-sectional study of 799 MSM aged 16-50 years was conducted in Vietnam in 2017-2018. Information was collected on risk behaviours, and knowledge of HPV and anal cancer; rectal swabs were taken to detect anal HPV infection. An in-house polymerase chain reaction and Genoflow HPV array test kit were used for HPV detection and genotyping. RESULTS: The median age of the study participants was 25 years (range 18-52). Overall prevalence of any HPV and HPV16/18 infection was 32.3% and 11.0%, respectively. A higher prevalence of high-risk HPV infection to all 14 types tested was found in Ho Chi Minh City (30.9%) than in Hanoi (18.4%). High-risk HPV infection was associated with inconsistent condom use and history of engaging in sex under the influence of drugs (adjusted odds ratio (aOR), 2.27; 95% CI, 1.48-10.67), as well as having multiple sexual partners (aOR, 1.01; 95% CI, 1.00-1.02). CONCLUSIONS: High-risk anal HPV infections in Vietnamese MSM were significantly associated with risky sexual behaviours. A targeted HPV vaccination strategy would have substantial benefit for MSM in Vietnam.

Polyketides and Meroterpenes from the Marine-Derived Fungi Aspergillus unguis 158SC-067 and A. flocculosus 01NT-1.1.5 and Their Cytotoxic and Antioxidant Activities.

Ten secondary metabolites, including a new grifolin analog, grifolin B (1); a new homovalencic acid derivative, 12-hydroxyhomovalencic acid (7); and a compound isolated from a natural source for the first time (9), along with seven known compounds, grifolin (2), averantin (3), 7-chloroaverantin (4), 1'-O-methylaverantin (5), 7-hydroxy-2-(2-hydroxypropyl)-5-pentylchromone (6), homovalencic acid (8), and bekeleylactone E (10), were isolated from two fungal strains. The structures of 1-10 were identified by detailed analysis and comparison of their spectroscopic data with literature values. Compounds 9 and 10 showed moderate cytotoxic activity against a panel of cancer cell lines (PC-3, HCT-15, MDA-MB-231, ACHN, NCI-H23, NUGC-3), with the GI50 values ranging from 1.1 µM to 3.6 µM, whereas 1 displayed a weak 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity without cytotoxicity against all tested cell lines.

Effectiveness and Tolerability of First-Line Afatinib for Advanced EGFR-Mutant Non-Small Cell Lung Cancer in Vietnam.

BACKGROUND: We aimed to evaluate the effectiveness and tolerability of Afatinib as first-line treatment of advanced epidermal growth factor receptor (EGFR) mutant non small cell lung cancer (NSCLC) in a real-world setting. PATIENTS AND METHODS: This is a retrospective study of Vietnamese patients  with advanced EGFR-mutant NSCLC treated with first-line afatinib at the National Cancer Hospital from 1st January 2018 to 31st October 2020. Patients' demographic, clinical and treatment data were captured. Objective response rate (ORR), disease control rate (DCR), time to treatment failure (TTF) and tolerability were evaluated. We used Kaplan-Meier curve and log-rank test for survival, and Cox regression model for multivariate analysis. RESULTS: A total of 44 patients were included. Common EGFR mutations (Del 19/L858R) were detected in 61% patients. Fifty percent of patients with uncommon mutations had compound mutations of G719X, L861Q and S768I. The ORR was 75% while DCR rate was 98%. The median TTF was 12.3 months (95% CI: 7.2-17.3); the mTTFs were 12.3 and 10.8 months for patients with common and uncommon mutations (p = 0.001), respectively, and 14.0 and 7.5 months for patients with Del 19 and L858R mutations (p = 0.067), respectively. Afatinib 30 mg once daily was the most common starting (77%) and maintenance (64%) doses. The mTTFs were 12.3 and 7.5 months for patients with 30 mg starting dose vs 40 mg dose (p = 0.256), respectively. Diarrhea, skin rash, paronychia and fatigue were observed in 32%, 30%, 25% and 9%, respectively. There was no grade 4 toxicity except three patients with grade 3 paronychia. CONCLUSIONS: First-line afatinib is beneficial for Vietnamese patients with advanced EGFR-mutant NSCLC with a good response rate and prolonged TTF with manageable adverse event profile. Baseline brain metastasis status and starting doses do not significantly impact TTF.
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New Polyenes from the Marine-Derived Fungus Talaromyces cyanescens with Anti-Neuroinflammatory and Cytotoxic Activities.

Three new polyene compounds, talacyanols A-C (1-3), along with two known compounds, ramulosin (4) and eurothiocin A (5), were isolated from the marine fungus Talaromyces cyanescens derived from a seaweed Caulerpa sp. Structures of 1-5 were established by one-dimensional and two-dimensional (1D/2D) NMR, HR-ESIMS, and the modified Mosher's methods, as well as comparison with previously reported literature data. All the compounds (1-5) were tested for their in vitro cytotoxic and anti-neuroinflammatory activities. Among them, 1 showed moderate cytotoxic activity against a panel of cancer cell lines (HCT-15, NUGC-3, NCI-H23, ACHN, PC-3, and MDA-MB-231) with GI50 values ranging from 44.4 to 91.6 µM, whereas compounds 2 and 5 exhibited anti-neuroinflammatory effect without cytotoxicity against all the tested cell lines.

Recent Progress and Advances of Multi-Stimuli-Responsive Dendrimers in Drug Delivery for Cancer Treatment.

Despite the fact that nanocarriers as drug delivery systems overcome the limitation of chemotherapy, the leakage of encapsulated drugs during the delivery process to the target site can still cause toxic effects to healthy cells in other tissues and organs in the body. Controlling drug release at the target site, responding to stimuli that originated from internal changes within the body, as well as stimuli manipulated by external sources has recently received significant attention. Owning to the spherical shape and porous structure, dendrimer is utilized as a material for drug delivery. Moreover, the surface region of dendrimer has various moieties facilitating the surface functionalization to develop the desired material. Therefore, multi-stimuli-responsive dendrimers or 'smart' dendrimers that respond to more than two stimuli will be an inspired attempt to achieve the site-specific release and reduce as much as possible the side effects of the drug. The aim of this review was to delve much deeper into the recent progress of multi-stimuli-responsive dendrimers in the delivery of anticancer drugs in addition to the major potential challenges.

Soy Lecithin-Derived Liposomal Delivery Systems: Surface Modification and Current Applications.

The development of natural phospholipids for nanostructured drug delivery systems has attracted much attention in the past decades. Lecithin that was derived from naturally occurring in soybeans (SL) has introduced some auspicious accomplishments to the drug carrying aspect, like effectual encapsulation, controlled release, and successful delivery of the curative factors to intracellular regions in which they procure these properties from their flexible physicochemical and biophysical properties, such as large aqueous center and biocompatible lipid, self-assembly, tunable properties, and high loading capacity. Despite the almost perfect properties as a drug carrier, liposome is known to be quite quickly eliminated from the body systems. The surface modification of liposomes has been investigated in many studies to overcome this drawback. In this review, we intensively discussed the surface-modified liposomes that enhancing the targeting, cellular uptake, and therapeutic response. Moreover, the recent applications of soy lecithin-derived liposome, focusing on cancer treatment, brain targeting, and vaccinology, are also summarized.