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Turkish Journal of Medical Sciences 2023Rheumatoid arthritis (RA) is a chronic inflammatory disease affecting mostly small joints, such as hand and foot joints symmetrically with irreversible joint...
BACKGROUND/AIM
Rheumatoid arthritis (RA) is a chronic inflammatory disease affecting mostly small joints, such as hand and foot joints symmetrically with irreversible joint destruction. In this study, the relationship between CD39 expression and the treatment response of RA patients was examined to investigate its potential as a biomarker that demonstrates treatment response.
MATERIALS AND METHODS
This study included 77 RA patients and 40 healthy controls (HC). The RA patients were divided into 2 groups based on their response to RA treatment, those with a good response to methotrexate (MTX) monotherapy and those with an inadequate response based on the American College of Rheumatology and the European League Against Rheumatism response criteria. Various immunological parameters and Disease Activity Score in 28 Joints (DAS28) were examined between the groups using the Student's t-test.
RESULTS
The monocytic myeloid-derived suppressor cell (M-MDSC) percentage was higher in the RA patient group versus the HC group. The CD39 expression in the T lymphocytes were higher in patients that responded well to the MTX compared to those showing inadequate response. Additionally, s negative correlation was found between the DAS28 and CD39 in the T cells.
CONCLUSION
The results showed that the improvement in treatment response to the therapy in RA patients could be because of the enhancement in the CD39/adenosine (ADO) pathway. Therefore, therapies targeting the CD39/ADO pathway in T cells may improve RA treatments.
Topics: Humans; Arthritis, Rheumatoid; Methotrexate; Female; Male; Apyrase; Middle Aged; Antirheumatic Agents; Adult; Biomarkers; Treatment Outcome; Antigens, CD; Case-Control Studies; Aged; T-Lymphocytes
PubMed: 38813034
DOI: 10.55730/1300-0144.5672 -
Asian Pacific Journal of Cancer... May 2024Several studies of multi-drug regimens for osteosarcoma have shown different efficacies and are still controversial. Meanwhile, chemotherapy options have remained... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Several studies of multi-drug regimens for osteosarcoma have shown different efficacies and are still controversial. Meanwhile, chemotherapy options have remained largely unchanged over a couple of decades. This study is designed to ascertain the outcome and safety of Methotrexate, Doxorubicin, and Cisplatin regimen for chemotherapy in osteosarcoma patients through the utilization of meta-analysis.
METHODS
We interrogated trials that compared the MAP regimen with other regimens as chemotherapy for osteosarcoma from several databases encompassing PubMed, Science Direct, and grey literature (Google Scholar) until December 2022. The analyzed outcomes including Event-Free Survival (EFS), Overall Survival (OS), Tumor Necrosis (TN) rate, and Adverse Event (AE) were then analyzed using RevMan 5.4 software in fixed or random effect models.
RESULTS
Our meta-analysis comprised 8 prospective articles that evaluated a cumulative number of 2920 OS patients. The analysis results indicated no meaningful difference in 5-year EFS (OR=0.99, 95% CI=0.77-1.27, [P = 0.91]) and neoadjuvant chemotherapy response (TN) (OR=0.76, 95% CI=0.49-1.17, [P = 0.22]) between the MAP and control groups. Furthermore, 5-year OS analysis revealed a significant association in the control group (OR=0.82, 95% CI=0.68-0.99, [P = 0.04]). However, the control group was associated with statistically meaningful AE compared to the MAP group, particularly in thrombocytopenia (OR=0.46, 95% CI=0.23-0.90, [P = 0.02]) and fever (OR=0.34, 95% CI=0.26-0.46, [P < 0.00001]).
CONCLUSION
The present meta-analysis showed that the MAP regimen remains preferable in treating osteosarcoma patients despite no significant outcome compared to the other regimens considering the less frequent AE in the MAP regimen.
Topics: Osteosarcoma; Humans; Methotrexate; Doxorubicin; Cisplatin; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Patient Safety; Prognosis; Survival Rate; Treatment Outcome
PubMed: 38809621
DOI: 10.31557/APJCP.2024.25.5.1497 -
BMC Oral Health May 2024This study assessed the effect of cevimeline and different concentrations of gum arabic on the parotid gland of rats being given xerostomia-inducing methotrexate. (Comparative Study)
Comparative Study
OBJECTIVE
This study assessed the effect of cevimeline and different concentrations of gum arabic on the parotid gland of rats being given xerostomia-inducing methotrexate.
METHODS
One hundred twenty-five rats were divided into five equal groups of twenty-five each. The rats in Group I received basic diets, while those in Groups II, III, IV, and V received 20 mg/kg MTX as a single intraperitoneal dose on day one. Group III received 10 mg/kg CVM dissolved in saline orally and daily, and the other two groups aqueous suspension of GA. Therefore, Group IV received 2 ml/kg suspension orally and daily, while Group V received 3 ml/kg suspension orally and daily. After 9 days, the parotid glands were dissected carefully and prepared for hematoxylin and eosin (H&E) staining as a routine histological stain and caspase-3 and Ki67 immunohistochemical staining. Quantitative data from α-Caspase-3 staining and Ki67 staining were statistically analysed using one-way ANOVA followed by Tukey's multiple comparisons post hoc test.
RESULTS
Regarding caspase-3 and Ki67 immunohistochemical staining, one-way ANOVA revealed a significant difference among the five groups. For Caspase-3, the highest mean value was for group II (54.21 ± 6.90), and the lowest mean value was for group I (15.75 ± 3.67). The other three groups had mean values of 31.09 ± 5.90, 30.76 ± 5.82, and 20.65 ± 3.47 for groups III, IV, and V, respectively. For Ki67, the highest mean value was for group I (61.70 ± 6.58), and the lowest value was for group II (18.14a ± 5.16). The other three groups had mean values of 34.4 ± 9.27, 48.03 ± 8.40, and 50.63 ± 8.27 for groups III, IV, and V, respectively.
CONCLUSION
GA, rather than the normally used drug CVM, had a desirable effect on the salivary glands of patients with xerostomia.
Topics: Animals; Rats; Xerostomia; Parotid Gland; Ki-67 Antigen; Methotrexate; Gum Arabic; Thiophenes; Caspase 3; Male; Rats, Wistar; Quinuclidines
PubMed: 38807094
DOI: 10.1186/s12903-024-04374-8 -
RMD Open May 2024To assess the safety and efficacy of upadacitinib versus adalimumab from SELECT-COMPARE over 5 years. (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
OBJECTIVES
To assess the safety and efficacy of upadacitinib versus adalimumab from SELECT-COMPARE over 5 years.
METHODS
Patients with rheumatoid arthritis and inadequate response to methotrexate were randomised to receive upadacitinib 15 mg once daily, placebo or adalimumab 40 mg every other week, all with concomitant methotrexate. By week 26, patients with insufficient response to randomised treatment were rescued; patients remaining on placebo switched to upadacitinib. Patients completing the 48-week double-blind period could enter a long-term extension. Safety and efficacy were assessed through week 264, with radiographic progression analysed through week 192. Safety was assessed by treatment-emergent adverse events (TEAEs). Efficacy was analysed by randomised group (non-responder imputation (NRI)) or treatment sequence (as observed).
RESULTS
Rates of TEAEs were generally similar with upadacitinib versus adalimumab, although numerically higher rates of herpes zoster, lymphopenia, creatine phosphokinase elevation, hepatic disorder and non-melanoma skin cancer were reported with upadacitinib. Numerically greater proportions of patients randomised to upadacitinib versus adalimumab achieved clinical responses (NRI); Clinical Disease Activity Index remission (≤2.8) and Disease Activity Score based on C reactive protein <2.6 were achieved by 24.6% vs 18.7% (nominal p=0.042) and 31.8% vs 23.2% (nominal p=0.006), respectively. Radiographic progression was numerically lower with continuous upadacitinib versus adalimumab at week 192.
CONCLUSION
The safety profile of upadacitinib through 5 years was consistent with the known safety profile of upadacitinib, with no new safety risks. Clinical responses were numerically higher with upadacitinib versus adalimumab at 5 years. Upadacitinib demonstrates a favourable benefit-risk profile for long-term rheumatoid arthritis treatment.
TRIAL REGISTRATION NUMBER
NCT02629159.
Topics: Humans; Arthritis, Rheumatoid; Adalimumab; Heterocyclic Compounds, 3-Ring; Female; Antirheumatic Agents; Male; Middle Aged; Treatment Outcome; Double-Blind Method; Adult; Methotrexate; Aged; Drug Therapy, Combination
PubMed: 38806190
DOI: 10.1136/rmdopen-2023-004007 -
The Journal of Physical Chemistry. B Jun 2024It is still a puzzle that has not been entirely solved how migratory birds utilize the Earth's magnetic field for biannual migration. The most consistent explanation...
It is still a puzzle that has not been entirely solved how migratory birds utilize the Earth's magnetic field for biannual migration. The most consistent explanation thus far is rooted in the modulation of the biological function of the cryptochrome 4 (Cry4) protein by an external magnetic field. This phenomenon is closely linked with the flavin adenine dinucleotide (FAD) cofactor that is noncovalently bound in the protein. Cry4 is activated by blue light, which is absorbed by the FAD cofactor. Subsequent electron and proton transfers trigger radical pair formation in the protein, which is sensitive to the external magnetic field. An important long-lasting redox state of the FAD cofactor is the signaling (FADH) state, which is present after the transient electron transfer steps have been completed. Recent experimental efforts succeeded in crystallizing the Cry4 protein from (ClCry4) with all of the important residues needed for protein photoreduction. This specific crystallization of Cry4 protein so far is the only avian cryptochrome crystal structure available, which, however, has great similarity to the Cry4 proteins of night migratory birds. The previous experimental studies of the ClCry4 protein included the absorption properties of the protein in its different redox states. The absorption spectrum of the FADH state demonstrated a peculiar red shift compared to the photoabsorption properties of the FAD cofactor in its FADH state in other Cry proteins from other species. The aim of this study is to understand this red shift by employing the tools of computational microscopy and, in particular, a QM/MM approach that relies on the polarizable embedding approximation.
Topics: Cryptochromes; Flavin-Adenine Dinucleotide; Animals; Avian Proteins; Oxidation-Reduction
PubMed: 38805723
DOI: 10.1021/acs.jpcb.4c00710 -
Medical Sciences (Basel, Switzerland) May 2024Gastric cancer has been demonstrating a reduction in the number of cases over the past decades, largely attributed to advancements in public health practices and...
Gastric cancer has been demonstrating a reduction in the number of cases over the past decades, largely attributed to advancements in public health practices and increased accessibility to educational initiatives for the general population. Nevertheless, it persists as the third leading cause of mortality globally among both men and women. These fatalities are typically associated with delayed disease detection. The current study assessed the levels of homocysteine, vitamin B12, and folic acid as a means of establishing a screening biomarker profile that could be integrated into routine testing protocols to facilitate swift diagnosis of the illness. A total of 207 control subjects and 207 individuals with gastric cancer were scrutinized, with biochemical measurements conducted using chemiluminescence for homocysteine, folic acid, and vitamin B12. The two groups were matched based on age, tumor location, subtype, tumor classification, presence of Epstein-Barr Virus infection (EBV), and Helicobacter pylori (). Significant statistical variances were identified in the mean levels of the triad of substances among cancer patients when compared to the control group for all corresponding variables. In conclusion, our study indicated that analyzing the triad of homocysteine, vitamin B12, and folic acid holds diagnostic value for gastric cancer and could potentially serve as an effective screening marker for this type of cancer in the future.
Topics: Humans; Stomach Neoplasms; Vitamin B 12; Folic Acid; Homocysteine; Male; Female; Middle Aged; Biomarkers, Tumor; Early Detection of Cancer; Aged; Adult; Case-Control Studies
PubMed: 38804380
DOI: 10.3390/medsci12020024 -
Scientific Reports May 2024Carbon nanotubes (CNTs) have the potential to serve as delivery systems for medicinal substances and gene treatments, particularly in cancer treatment. Co-delivery of...
Carbon nanotubes (CNTs) have the potential to serve as delivery systems for medicinal substances and gene treatments, particularly in cancer treatment. Co-delivery of curcumin (CUR) and Methotrexate (MTX) has shown promise in cancer treatment, as it uses fewer drugs and has fewer side effects. This study used MTX-conjugated albumin (BSA)-based nanoparticles (BSA-MTX) to enhance and assess the efficiency of CUR. In-vitro cytotoxicity tests, DLS, TEM, FTIR, UV/Vis, SEM, and DSC studies assessed the formulations' physical and chemical properties. The Proteinase K enzyme was used to severe amidic linkages between MTX and BSA. The findings demonstrated the efficacy of using ƒ-MWCNT-CUR-BSA-MTX as a vehicle for efficient co-delivery of CUR and MTX in cancer treatment. The MTT colorimetric method was used to evaluate the effect of chemical and medicinal compounds. Cell division was studied using the MTT method to investigate the effect of pure MWCNT, pure CUR, MTX-BSA, and ƒ-MWCNT-CUR-MTX-BSA. Studies on cell lines have shown that the combination of curcumin and MTX with CNT can increase and improve the effectiveness of both drugs against cancer. A combination of drugs curcumin and methotrexate simultaneously had a synergistic effect on MCF-7 cells, which indicated that these drugs could potentially be used as a strategy for both prevention and treatment of breast cancer. Also, ƒ-MWCNT-CUR-MTX-BSA was found to have a significant effect on cancer treatment with minimal toxicity compared to pure curcumin, pure MTX-BSA, MTX, and ƒ-MWCNT alone. Unique properties such as a high ratio of specific surface area to volume, high chemical stability, chemical adsorption ability, high capacity of drug and biomolecules of carbon nanotubes, as well as multiple drug loading at the same time The combination of ƒ-MWCNT-CUR-BSA MTX significantly impacts cancer therapy), are desirable as an alternative option for targeted drug delivery and high therapeutic efficiency.
Topics: Nanotubes, Carbon; Methotrexate; Humans; Curcumin; Nanoparticles; Drug Delivery Systems; Serum Albumin, Bovine; Antineoplastic Agents; MCF-7 Cells; Drug Carriers; Cell Survival; Cell Line, Tumor
PubMed: 38802442
DOI: 10.1038/s41598-024-59745-6 -
Scientific Reports May 2024The effect of high-dose pyridoxine (PN) on activity of 5-fluorouracil (FUra) and folinic acid (FA)-containing regimens was studied in 50 patients including 14 with...
The effect of high-dose pyridoxine (PN) on activity of 5-fluorouracil (FUra) and folinic acid (FA)-containing regimens was studied in 50 patients including 14 with digestive tract, and 36 with breast carcinomas (BC) in advanced stages with poor prognostic characteristics. Patients with colorectal, and pancreas adenocarcinoma received oxaliplatin, irinotecan, FUra, FA (Folfirinox), and patients with squamous cell carcinoma of the esophagus had paclitaxel, carboplatin, FUra, FA (TCbF). Patients with BC received AVCF (doxorubicin, vinorelbine, cyclophosphamide, FUra, FA) followed by TCbF or TCbF only, and patients who overexpressed HER2 received TCbF plus trastuzumab and pertuzumab. PN (1000-3000 mg/day iv) preceded each administration of FUra and FA. 47 patients (94%) responded, including 16 (32%) with CR. Median tumor reduction was 93%. Median event-free survival (EFS) was 37.7 months. The 25 patients with tumor shrinkage ≥ 91% had EFS of 52% from 42 months onwards. Unexpected toxicity did not occur. PN enhances potency of chemotherapy regimens comprising FUra and FA.
Topics: Humans; Fluorouracil; Leucovorin; Pyridoxine; Female; Middle Aged; Aged; Male; Antineoplastic Combined Chemotherapy Protocols; Adult; Breast Neoplasms; Neoplasm Staging; Treatment Outcome
PubMed: 38802419
DOI: 10.1038/s41598-024-62860-z -
The Western Journal of Emergency... May 2024Ectopic pregnancies are a significant cause of morbidity and mortality in the first trimester of pregnancy. Hospital protocols requiring a specific beta-human chorionic...
INTRODUCTION
Ectopic pregnancies are a significant cause of morbidity and mortality in the first trimester of pregnancy. Hospital protocols requiring a specific beta-human chorionic gonadotropin (β-hCG) level to qualify for diagnostic testing (pelvic ultrasound) can delay diagnosis and treatment. In this study we sought to determine the relationship between β-hCG level and the size of ectopic pregnancy with associated outcomes.
METHODS
We performed a retrospective case review of patients diagnosed with ectopic pregnancy in an urban, academic emergency department specializing in obstetrical care, from January 1, 2015-December 31, 2017. Variables extracted included presentation, treatment, adverse outcomes, and rates of rupture.
RESULTS
We identified 519 unique ectopic pregnancies. Of those ectopic pregnancies, 22.9% presented with evidence of rupture on ultrasound, and 14.4% showed evidence of hemodynamic instability (pulse >100 beats per minute; systolic blood pressure <90 millimeters of mercury; or evidence of significant blood loss) on presentation. Medical management outcomes were as follows: of 177 patients who received single-dose methotrexate, 14.7% failed medical management and required surgical intervention; of 46 who received multi-dose methotrexate, 36.9% failed medical management and required surgical intervention. Ultimately, 55.7% of patients required operative management of their ectopic pregnancy. Mean β-hCG level at initial presentation was 7,096 milli-international units per milliliter (mIU/mL) (SD 88,872 mIU/mL) with a median of 1,289 mIU/mL; 50.4% of ectopic pregnancies presented with β-hCG levels less than the standard discriminatory zone of 1,500 mIU/mL. Additionally, 44% of the patients who presented with evidence of rupture had β-hCG levels less than 1,500 mIU/mL. Comparison of size of ectopic pregnancy (based on maximum dimension in millimeters) to β-hCG levels revealed a very weak correlation (r = 0.144, ), and detection of ectopic pregnancies by ultrasound was independent of β-hCG levels.
CONCLUSION
Levels of β-hCG do not correlate with the presence or size of an ectopic pregnancy, indicating need for diagnostic imaging regardless of β-hCG level in patients with clinical suspicion for ectopic pregnancy. Almost one-sixth of patients presented with evidence of hemodynamic instability, and approximately one quarter of patients presented with evidence of rupture requiring emergent operative management. Ultimately, more than half of patients required an operative procedure to definitively manage their ectopic pregnancy.
Topics: Humans; Female; Pregnancy; Pregnancy, Ectopic; Retrospective Studies; Chorionic Gonadotropin, beta Subunit, Human; Adult; Emergency Service, Hospital; Methotrexate; Abortifacient Agents, Nonsteroidal; Pregnancy Trimester, First; Ultrasonography, Prenatal
PubMed: 38801051
DOI: 10.5811/westjem.18396 -
Frontiers in Immunology 2024The prognosis for unresectable intrahepatic cholangiocarcinoma (ICC) is poor and the efficacy of traditional chemotherapy remains unsatisfactory. Hepatic arterial...
BACKGROUND
The prognosis for unresectable intrahepatic cholangiocarcinoma (ICC) is poor and the efficacy of traditional chemotherapy remains unsatisfactory. Hepatic arterial infusion chemotherapy (HAIC) with oxaliplatin, leucovorin, and 5-fluorouracil (FOLFOX) is effective in patients with unresectable ICC. In this study, we determined the preliminary clinical efficacy and safety of lenvatinib plus durvalumab combined with FOLFOX-HAIC in patients with untreated, unresectable ICC.
MATERIALS AND METHODS
Between July 2021 and July 2023, patients with unresectable ICC who initially received lenvatinib plus durvalumab combined with FOLFOX-HAIC at the Sun Yat-Sen University Cancer Center (SYSUCC) were reviewed for eligibility. Efficacy was evaluated by tumor response rate and survival, and safety was assessed by the frequency of key adverse events (AEs).
RESULTS
A total of 28 eligible patients were enrolled. The objective response rates (ORRs) based on mRECIST and RECIST 1.1 criteria were 65.2% and 39.1%, respectively. The median OS was 17.9 months (95% CI, 5.7-30.1) and the median PFS was 11.9 months (95% CI, 6.7-17.1). Most patients (92.9%) experienced adverse events (AEs), whereas 46.5% (13/28) experienced grade 3 or 4 AEs.
CONCLUSION
Lenvatinib plus durvalumab combined with FOLFOX-HAIC showed promising antitumor activity and manageable AEs in patients with treatment-naive unresectable ICC. This regimen may be suitable as a novel first-line treatment option for this patient population.
Topics: Humans; Male; Antineoplastic Combined Chemotherapy Protocols; Female; Phenylurea Compounds; Middle Aged; Quinolines; Aged; Cholangiocarcinoma; Antibodies, Monoclonal; Bile Duct Neoplasms; Infusions, Intra-Arterial; Leucovorin; Adult; Fluorouracil; Treatment Outcome; Organoplatinum Compounds; Hepatic Artery; Retrospective Studies
PubMed: 38799453
DOI: 10.3389/fimmu.2024.1397827