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1.
In Vivo ; 38(4): 1740-1749, 2024.
Article in English | MEDLINE | ID: mdl-38936885

ABSTRACT

BACKGROUND/AIM: To date, therapeutic options for T-cell acute lymphoblastic leukemia (T-ALL) remain very limited. This study evaluated the efficacy of monotherapies and combination therapies including a selective BCL-2 inhibitor for T-ALL cell lines, namely Jurkat, CCRF-CEM, and Loucy. MATERIALS AND METHODS: Loucy is an early T-precursor ALL (ETP-ALL) cell line characterized by an immature phenotype, whereas Jurkat and CCRF-CEM are late T-cell progenitor ALL (LTP-ALL) cell lines. Monotherapy was conducted with venetoclax, cytarabine, bendamustine, or azacytidine, whereas combination therapy was performed with venetoclax plus cytarabine, venetoclax plus bendamustine, or venetoclax plus azacytidine. Cell viability assay was conducted after 48 h using Trypan blue and the 3-(4, 5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS). Statistical analysis for evaluating synergistic interactions between anticancer drugs was performed by using the SynergyFinder Plus and drc R package. RESULTS: Adding venetoclax to cytarabine, bendamustine, or azacitidine achieved an additive effect, with Loewe synergic scores ranging from -10 to 10 in Jurkat and CCRF-CEM. Conversely, the combination of venetoclax and cytarabine displayed an additive effect (Loewe synergic score: 8.45 and 5.82 with MTS and Trypan blue assays, respectively), whereas venetoclax plus bendamustine or azacitidine exhibited a synergistic effect (Loewe synergic score >10 with MTS assay) in Loucy. Remarkably, the Bliss/Loewe score revealed that the combination of venetoclax and bendamustine was the most synergistic, yielding a score of 13.832±0.55. CONCLUSION: The combination of venetoclax and bendamustine demonstrated the greatest synergistic effect in suppressing ETP-ALL cell proliferation. Further studies are warranted to determine the mechanisms for the synergism between venetoclax and bendamustine in high-risk T-ALL.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Bendamustine Hydrochloride , Bridged Bicyclo Compounds, Heterocyclic , Drug Synergism , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma , Sulfonamides , Humans , Bendamustine Hydrochloride/administration & dosage , Bendamustine Hydrochloride/pharmacology , Bridged Bicyclo Compounds, Heterocyclic/pharmacology , Bridged Bicyclo Compounds, Heterocyclic/administration & dosage , Sulfonamides/administration & dosage , Sulfonamides/pharmacology , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/pathology , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cell Line, Tumor , Cell Survival/drug effects , Jurkat Cells , Apoptosis/drug effects , Cell Proliferation/drug effects
2.
Biosci Microbiota Food Health ; 43(1): 73-80, 2024.
Article in English | MEDLINE | ID: mdl-38188664

ABSTRACT

The reasons for sex-associated gut microbiota differences have not been determined, and although sex hormones, diet, and other factors are considered to contribute to them, many of these factors are age related. To shed light on this complex interplay, our study aimed to investigate and compare the gut microbial compositions of males and females across a broad range of ages, aiming to identify sex-associated disparities and potential causal factors. Our study encompassed a comprehensive analysis of gut microbiota data obtained from 444 Japanese individuals, ranging from newborns to centenarians, sourced from the DNA Data Bank of Japan. We categorized the subjects into 13 distinct age groups and examined their relative microbial abundances, as well as alpha and beta diversities, in relation to sex and age. No difference was observed between gut microbiota relative abundances or alpha diversities between men and women at any age. However, the study showed that the heterogeneity of gut microbiota among women in their 20s was greater than in men. To confirm the general occurrence of this difference, we conducted additional analyses using seven datasets: three from Japan and four from other countries. Interestingly, this variance was particularly noticeable within Japanese women. We also showed a potential link between the observed heterogeneity and dietary fiber intake. It is hoped this study will provide clues that aid in the identification of factors responsible for sex-associated differences in gut microbiota compositions.

3.
In Vivo ; 38(1): 372-379, 2024.
Article in English | MEDLINE | ID: mdl-38148060

ABSTRACT

BACKGROUND/AIM: This study evaluated the possibility of clinical use of circulating-tumor DNA (ctDNA) as a biomarker to determine up-front autologous stem cell transplantation (auto-SCT) for patients with high-risk diffuse large B-cell lymphoma (DLBCL) in practice. PATIENTS AND METHODS: To explore the dynamics of ctDNA in DLBCL, blood samples were collected sequentially before and after treatment from patients with newly diagnosed DLBCL who received rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy. To conduct ctDNA genotyping and ctDNA monitoring simultaneously, targeted sequencing by cancer personalized profiling using deep sequencing was used. RESULTS: Ten patients between the ages of 50 and 60 years were enrolled. Based on the international prognostic index (IPI), seven patients were classified as high-IPI-risk group, and three patients were classified as low-IPI-risk group. The IPI risk group correlated with total metabolic tumor volume. All patients completed six cycles of R-CHOP chemotherapy, and seven patients achieved complete response. Changes in ctDNA mutation numbers did not correlate with changes in PET scan images and treatment response. In most high-risk patients, new mutations appeared in ctDNA after completion of chemotherapy that conceivably marked resistant clones. Notably, disease relapse did not occur in high-risk patients with poor prognostic mutations who underwent autologous SCT. CONCLUSION: ctDNA monitoring was meaningful in high-risk patients. Moreover, ctDNA and well-known prognostic factors should be considered in the decision making for auto-SCT. If a new genetic mutation in ctDNA with a negative prognosis would emerge during treatment, high-risk patients should consider auto-SCT.


Subject(s)
Hematopoietic Stem Cell Transplantation , Lymphoma, Large B-Cell, Diffuse , Humans , Middle Aged , Pilot Projects , Neoplasm Recurrence, Local/drug therapy , Transplantation, Autologous , Stem Cell Transplantation , Lymphoma, Large B-Cell, Diffuse/diagnosis , Lymphoma, Large B-Cell, Diffuse/drug therapy , Lymphoma, Large B-Cell, Diffuse/genetics , Prognosis , Cyclophosphamide/therapeutic use , Prednisone/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Doxorubicin/therapeutic use , Doxorubicin/adverse effects , Vincristine/therapeutic use , DNA
4.
Indian J Med Microbiol ; 46: 100426, 2023.
Article in English | MEDLINE | ID: mdl-37945119

ABSTRACT

PURPOSE: Group B Streptococcus (GBS) colonization and vaginal microbiome (VMB) dysbiosis are associated with adverse perinatal outcomes. However, the role of GBS colonization in maternal VMB remains unclear. Herein, we aimed to investigate this relationship and identify additional pathogens associated with GBS colonization for potential implications in understanding their clinical significance. MATERIALS AND METHODS: Vaginal swab samples were obtained before delivery from nine women with normal pregnancies for GBS detection and 16S rRNA gene sequencing. The diversity analysis and community state types clustering were used to compare the GBS-positive vs. GBS-negative groups. ANCOM-BC was implemented to identify differentially abundant microbes (DAMs) associated with GBS colonization. The correlation and receiver operating characteristic analysis were used to evaluate the relationship between DMAs and clinical parameters. RESULTS: There were 6/9 (66,7%) GBS-negative pregnant women. The α-diversity index (p â€‹= â€‹0.71 for observed operational taxonomic units and p â€‹= â€‹0.90 for Shannon diversity), ß-diversity index (p â€‹= â€‹0.583), and community state types clustering (p â€‹= â€‹0.23) were not significantly different between the GBS-positive and -negative groups. Four DAMs, namely, Actinomyces, Shigella, Fenollaria, and Gemella, were significantly associated with GBS colonization, reflecting the dynamicity of the gestational VMB. Their abundances were negatively correlated with birth weight and had acceptable discriminating ability in premature membrane rupture (area under the curve, 0.9). CONCLUSIONS: Despite the absence of significant effects on overall VMB composition, our preliminary results investigated that maternal GBS colonization related to high abundance of four pathogens with potential clinical utility as microbial signatures.


Subject(s)
Microbiota , Pregnancy Complications, Infectious , Streptococcal Infections , Pregnancy , Female , Humans , Pilot Projects , RNA, Ribosomal, 16S/genetics , Streptococcus agalactiae/genetics
5.
Microorganisms ; 11(6)2023 May 27.
Article in English | MEDLINE | ID: mdl-37374919

ABSTRACT

Uterine cervical cancer (CC) is a complex, multistep disease primarily linked to persistent infection with high-risk human papillomavirus (HR-HPV). However, it is widely acknowledged that HR-HPV infection alone cannot account for the formation and progression of CC. Emerging evidence suggests that the cervicovaginal microbiome (CVM) also plays a significant role in HPV-related CC. Certain bacteria, such as Fusobacterium spp., Porphyromonas, Prevotella, and Campylobacter, are currently being considered as potential microbiomarkers for HPV-positive CC. However, the composition of the CVM in CC is inconsistent; thus, further studies are needed. This review comprehensively discusses the complex interplay between HPV and the CVM in cervical carcinogenesis. It is postulated that the dynamic interaction between HPV and the CVM creates an imbalanced cervicovaginal microenvironment that triggers dysbiosis, enhances HPV persistence, and promotes cervical carcinogenesis. Moreover, this review aims to provide updated evidence on the potential role of bacteriotherapy, particularly probiotics, in the treatment of CC.

6.
Microorganisms ; 10(12)2022 Dec 02.
Article in English | MEDLINE | ID: mdl-36557651

ABSTRACT

Group B Streptococcus (GBS, Streptococcus agalactiae) is a Gram-positive bacterium that is commonly found in the gastrointestinal and urogenital tracts. However, its colonization during pregnancy is an important cause of maternal and neonatal morbidity and mortality worldwide. Herein, we specifically looked at GBS in relation to the field of Obstetrics (OB) along with the field of Gynecology (GY). In this review, based on the clinical significance of GBS in the field of OBGY, topics of how GBS is being detected, treated, and should be prevented are addressed.

7.
Curr Issues Mol Biol ; 44(11): 5139-5152, 2022 Oct 23.
Article in English | MEDLINE | ID: mdl-36354662

ABSTRACT

Tumor budding (TB) is a small cluster of malignant cells at the invasive front of a tumor. Despite being an adverse prognosis marker, little research has been conducted on the tumor immune microenvironment of tumor buddings, especially in cervical cancer. Therefore, RNA sequencing was performed using 21 formalin-fixed, paraffin-embedded slides of cervical tissues, and differentially expressed genes (DEGs) were analyzed. Immune Pathway and Gene Database (IMPAGT) was generated for immune profiling. "Pathway in Cancer" was identified as the most enriched pathway for both up- and downregulated DEGs. Kyoto Encyclopedia of Genes and Genomes Mapper and Gene Ontology further revealed the activation of the PI3K/Akt signaling pathway. An IMPAGT analysis revealed immune dysregulation even at the tumor budding stage, especially in the PI3K/Akt/mTOR axis, with a high efficiency and integrity. These findings emphasized the clinical significance of tumor buddings and the necessity of blocking the overactivation of the PI3K/Akt/mTOR pathway to improve targeted therapy in cervical cancer.

8.
Genes (Basel) ; 13(8)2022 08 07.
Article in English | MEDLINE | ID: mdl-36011316

ABSTRACT

Tumor budding (TB) histology has become a critical biomarker for several solid cancers. Despite the accumulating evidence for the association of TB histology with poor prognosis, the biological characteristics of TB are little known about in the context related to the tumor immune microenvironment (TIME) in uterine cervical cancer (CC). Therefore, this study aimed to identify the transcriptomic immune profiles related to TB status and further provide robust medical evidence for clinical application. In our study, total RNA was extracted and sequenced from 21 CC tissue specimens. As such, 1494 differentially expressed genes (DEGs) between the high- and low-TB groups were identified by DESeq2. After intersecting the list of DEGs and public immune genes, we selected 106 immune-related DEGs. Then, hub genes were obtained using Least Absolute Shrinkage and Selection Operator regression. Finally, the correlation between the hub genes and immune cell types was analyzed and four candidate genes were identified (one upregulated (FCGR3B) and three downregulated (ROBO2, OPRL1, and NR4A2) genes). These gene expression levels were highly accurate in predicting TB status (area under the curve >80%). Interestingly, FCGR3B is a hub gene of several innate immune pathways; its expression significantly differed in the overall survival analysis (p = 0.0016). In conclusion, FCGR3B, ROBO2, OPRL1, and NR4A2 expression can strongly interfere with TB growth and replace TB to stratify CC patients.


Subject(s)
Transcriptome , Uterine Cervical Neoplasms , Computational Biology , Female , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Gene Regulatory Networks , Humans , Protein Interaction Maps/genetics , Transcriptome/genetics , Tumor Microenvironment/genetics , Uterine Cervical Neoplasms/genetics
9.
Micromachines (Basel) ; 13(4)2022 Mar 31.
Article in English | MEDLINE | ID: mdl-35457869

ABSTRACT

X-ray imaging machines are widely used in border control checkpoints or public transportation, for luggage scanning and inspection. Recent advances in deep learning enabled automatic object detection of X-ray imaging results to largely reduce labor costs. Compared to tasks on natural images, object detection for X-ray inspection are typically more challenging, due to the varied sizes and aspect ratios of X-ray images, random locations of the small target objects within the redundant background region, etc. In practice, we show that directly applying off-the-shelf deep learning-based detection algorithms for X-ray imagery can be highly time-consuming and ineffective. To this end, we propose a Task-Driven Cropping scheme, dubbed TDC, for improving the deep image detection algorithms towards efficient and effective luggage inspection via X-ray images. Instead of processing the whole X-ray images for object detection, we propose a two-stage strategy, which first adaptively crops X-ray images and only preserves the task-related regions, i.e., the luggage regions for security inspection. A task-specific deep feature extractor is used to rapidly identify the importance of each X-ray image pixel. Only the regions that are useful and related to the detection tasks are kept and passed to the follow-up deep detector. The varied-scale X-ray images are thus reduced to the same size and aspect ratio, which enables a more efficient deep detection pipeline. Besides, to benchmark the effectiveness of X-ray image detection algorithms, we propose a novel dataset for X-ray image detection, dubbed SIXray-D, based on the popular SIXray dataset. In SIXray-D, we provide the complete and more accurate annotations of both object classes and bounding boxes, which enables model training for supervised X-ray detection methods. Our results show that our proposed TDC algorithm can effectively boost popular detection algorithms, by achieving better detection mAPs or reducing the run time.

10.
Front Psychol ; 12: 654314, 2021.
Article in English | MEDLINE | ID: mdl-34177706

ABSTRACT

We describe an art-science project called "Feral Interactions-The Answer of the Humpback Whale" inspired by humpback whale songs and interactions between individuals based on mutual influences, learning process, or ranking in the dominance hierarchy. The aim was to build new sounds that can be used to initiate acoustic interactions with these whales, not in a one-way direction, as playbacks do, but in real interspecies exchanges. Thus, we investigated how the humpback whales generate sounds in order to better understand their abilities and limits. By carefully listening to their emitted vocalizations, we also describe their acoustic features and temporal structure, in a scientific way and also with a musical approach as it is done with musique concrète, in order to specify the types and the morphologies of whale sounds. The idea is to highlight the most precise information to generate our own sounds that will be suggested to the whales. Based on the approach developed in musique concrète, similarities with the sounds produced by bassoon were identified and then were processed to become "concrete sound elements." This analysis also brought us to design a new music interface that allows us to create adapted musical phrases in real-time. With this approach, interactions will be possible in both directions, from and to whales.

11.
BMC Infect Dis ; 12: 49, 2012 Mar 01.
Article in English | MEDLINE | ID: mdl-22375832

ABSTRACT

BACKGROUND: Early diagnosis of tuberculosis (TB) and multidrug resistant tuberculosis (MDR TB) is important for the elimination of TB. We evaluated the microscopic observation drug susceptibility (MODS) assay as a direct rapid drug susceptibility testing (DST) method for MDR-TB screening in sputum samples METHODS: All adult TB suspects, who were newly presenting to Pham Ngoc Thach Hospital from August to November 2008 were enrolled into the study. Processed sputum samples were used for DST by MODS (DST-MODS) (Rifampicin (RIF) 1 µg/ml and Isoniazid (INH) 0.4 µg/ml), MGIT culture (Mycobacterial Growth Indicator Tube) and Lowenstein Jensen (LJ) culture. Cultures positive by either MGIT or LJ were used for proportional DST (DST-LJ) (RIF 40 µg/ml and INH 0.2 µg/ml). DST profiles on MODS and LJ were compared. Discrepant results were resolved by multiplex allele specific PCR (MAS-PCR). RESULTS: Seven hundred and nine TB suspects/samples were enrolled into the study, of which 300 samples with DST profiles available from both MODS and DST-LJ were analyzed. Cording in MODS was unable to correctly identify 3 Mycobacteria Other Than Tuberculosis (MOTT) isolates, resulting in 3 false positive TB diagnoses. None of these isolates were identified as MDR-TB by MODS. The sensitivity and specificity of MODS were 72.6% (95%CI: 59.8, 83.1) and 97.9% (95%CI: 95.2, 99.3), respectively for detection of INH resistant isolates, 72.7% (95%CI: 30.9, 93.7) and 99.7% (95%CI: 98.1, 99.9), respectively for detecting RIF resistant isolates and 77.8% (95%CI: 39.9, 97.1) and 99.7% (95%CI: 98.1, 99.9), respectively for detecting MDR isolates. The positive and negative predictive values (PPV and NPV) of DST-MODS were 87.5% (95%CI: 47.3, 99.6) and 99.3% (95%CI: 97.5, 99.9) for detection of MDR isolates; and the agreement between MODS and DST-LJ was 99.0% (kappa: 0.8, P < 0.001) for MDR diagnosis. The low sensitivity of MODS for drug resistance detection was probably due to low bacterial load samples and the high INH concentration (0.4 µg/ml). The low PPV of DST-MODS may be due to the low MDR-TB rate in the study population (3.8%). The turnaround time of DST-MODS was 9 days and 53 days for DST-LJ. CONCLUSION: The DST-MODS technique is rapid with low contamination rates. However, the sensitivity of DST-MODS for detection of INH and RIF resistance in this study was lower than reported from other settings.


Subject(s)
Antitubercular Agents/pharmacology , Drug Resistance, Multiple, Bacterial , Microscopy/methods , Mycobacterium tuberculosis/isolation & purification , Tuberculosis, Multidrug-Resistant/diagnosis , Adult , Culture Media/chemistry , Early Diagnosis , Female , Humans , Isoniazid/pharmacology , Male , Mass Screening/methods , Microbial Sensitivity Tests/methods , Middle Aged , Mycobacterium tuberculosis/drug effects , Polymerase Chain Reaction , Rifampin/pharmacology , Sensitivity and Specificity , Vietnam
12.
N Engl J Med ; 351(17): 1741-51, 2004 Oct 21.
Article in English | MEDLINE | ID: mdl-15496623

ABSTRACT

BACKGROUND: Tuberculous meningitis kills or disables more than half of those affected with the disease. Previous studies have been too small to determine whether adjunctive treatment with corticosteroids can reduce the risk of disability or death among adults with tuberculous meningitis, and the effect of coinfection with the human immunodeficiency virus (HIV) is unclear. METHODS: We performed a randomized, double-blind, placebo-controlled trial in Vietnam in patients over 14 years of age who had tuberculous meningitis, with or without HIV infection, to determine whether adjunctive treatment with dexamethasone reduced the risk of death or severe disability after nine months of follow-up. We conducted prespecified subgroup analyses and intention-to-treat analyses. RESULTS: A total of 545 patients were randomly assigned to groups that received either dexamethasone (274 patients) or placebo (271 patients). Only 10 patients (1.8 percent) had been lost to follow-up at nine months of treatment. Treatment with dexamethasone was associated with a reduced risk of death (relative risk, 0.69; 95 percent confidence interval, 0.52 to 0.92; P=0.01). It was not associated with a significant reduction in the proportion of severely disabled patients (34 of 187 patients [18.2 percent] among survivors in the dexamethasone group vs. 22 of 159 patients [13.8 percent] in the placebo group, P=0.27) or in the proportion of patients who had either died or were severely disabled after nine months (odds ratio, 0.81; 95 percent confidence interval, 0.58 to 1.13; P=0.22). The treatment effect was consistent across subgroups that were defined by disease-severity grade (stratified relative risk of death, 0.68; 95 percent confidence interval, 0.52 to 0.91; P=0.007) and by HIV status (stratified relative risk of death, 0.78; 95 percent confidence interval, 0.59 to 1.04; P=0.08). Significantly fewer serious adverse events occurred in the dexamethasone group than in the placebo group (26 of 274 patients vs. 45 of 271 patients, P=0.02). CONCLUSIONS: Adjunctive treatment with dexamethasone improves survival in patients over 14 years of age with tuberculous meningitis but probably does not prevent severe disability.


Subject(s)
Dexamethasone/therapeutic use , Glucocorticoids/therapeutic use , Tuberculosis, Meningeal/drug therapy , AIDS-Related Opportunistic Infections/drug therapy , Adjuvants, Immunologic/therapeutic use , Adolescent , Adult , Aged , Aged, 80 and over , Dexamethasone/adverse effects , Double-Blind Method , Female , Glucocorticoids/adverse effects , HIV Infections/complications , Humans , Male , Middle Aged , Multivariate Analysis , Survival Analysis , Tuberculosis, Meningeal/complications , Tuberculosis, Meningeal/mortality
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