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Journal of Personalized Medicine May 2024The intestinal wound healing process is a complex event of three overlapping phases: exudative, proliferative, and remodeling. Although some mechanisms have been... (Review)
Review
BACKGROUND
The intestinal wound healing process is a complex event of three overlapping phases: exudative, proliferative, and remodeling. Although some mechanisms have been extensively described, the intestinal healing process is still not fully understood. There are some similarities but also some differences compared to other tissues. The aim of this systematic review was to summarize all studies with knockout (KO) experimental models in bowel anastomoses, underline any recent knowledge, and clarify further the cellular and molecular mechanisms of the intestinal healing process. A systematic review protocol was performed.
MATERIALS AND METHODS
Medline, EMBASE, and Scopus were comprehensively searched.
RESULTS
a total of eight studies were included. The silenced genes included interleukin-10, the four-and-one-half LIM domain-containing protein 2 (FHL2), cyclooxygenase-2 (COX-2), annexin A1 (ANXA-1), thrombin-activatable fibrinolysis inhibitor (TAFI), and heparin-binding epidermal growth factor (HB-EGF) gene. Surgically, an end-to-end bowel anastomosis was performed in the majority of the studies. Increased inflammatory cell infiltration in the anastomotic site was found in IL-10-, annexin-A1-, and TAFI-deficient mice compared to controls. COX-1 deficiency showed decreased angiogenesis at the anastomotic site. Administration of prostaglandin E2 in COX-2-deficient mice partially improved anastomotic leak rates, while treatment of ANXA1 KO mice with Ac2-26 nanoparticles reduced colitis activity and increased weight recovery following surgery.
CONCLUSIONS
our findings provide new insights into improving intestinal wound healing by amplifying the aforementioned genes using appropriate gene therapies. Further research is required to clarify further the cellular and micromolecular mechanisms of intestinal healing.
PubMed: 38929776
DOI: 10.3390/jpm14060553 -
PeerJ 2024To evaluate the efficacy and safety of Brolucizumab for neovascular age-related macular degeneration (n-AMD) through a systematic review and meta-analysis. (Meta-Analysis)
Meta-Analysis
BACKGROUND
To evaluate the efficacy and safety of Brolucizumab for neovascular age-related macular degeneration (n-AMD) through a systematic review and meta-analysis.
MATERIALS AND METHODS
Cochrane, PubMed, Embase, and Web of Science databases were comprehensively searched for relevant studies. Stata and RevMan5.4 were applied for meta-analysis and risk of bias assessment. Data on the best-corrected visual acuity (BCVA), central subfield thickness (CSFT), presence of intraretinal fluid (IRF) and/or subretinal fluid (SRF), participants with ≥1 serious adverse events, and participants with ≥1 adverse events were analyzed.
RESULTS
Six studies were finally included. Meta-analysis showed statistical differences in BCVA [SMD = -0.65, 95% CI [-0.17 to -0.23], < 0.05], the presence of IRF and/or SRF [RR = 0.67, 95% CI [0.56-0.79], < 0.05], and the safety of participants with ≥1 serious adverse events [RR = 0.57, 95% CI [0.39-0.84], < 0.05] between the experimental group and the control group. However, no statistical differences were observed in CSFT [SMD = -1.16, 95% CI [-2.79 to 0.47], > 0.05] or the safety of participants with ≥1 adverse events [RR = 1.07, 95% CI [0.97-1.17], > 0.05].
CONCLUSIONS
Compared to other anti-VEGF drugs such as Aflibercept and Ranibizumab, intravitreal injection of 6 mg Brolucizumab is more effective and safer for n-AMD, especially in the presence of IRF and/or SRF, and for participants with ≥1 serious adverse events.
Topics: Humans; Angiogenesis Inhibitors; Antibodies, Monoclonal, Humanized; Intravitreal Injections; Macular Degeneration; Treatment Outcome; Visual Acuity; Wet Macular Degeneration
PubMed: 38915383
DOI: 10.7717/peerj.17561 -
PloS One 2024Intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections have emerged as the most common therapeutic approach for the management of diabetic macular... (Meta-Analysis)
Meta-Analysis Comparative Study
Comparative efficacy of anti-vascular endothelial growth factor on diabetic macular edema diagnosed with different patterns of optical coherence tomography: A network meta-analysis.
Intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections have emerged as the most common therapeutic approach for the management of diabetic macular edema (DME). Despite their proven superiority over other interventions, there is a paucity of data regarding the relative effectiveness of anti-VEGF agents in treating DME diagnosed with different patterns of optical coherence tomography (OCT). In this regard, we conducted a systematic review and comparative analysis of the therapeutic efficacy of intravitreal bevacizumab, ranibizumab, aflibercept, and conbercept in the management of DME with diffuse retinal thickening (DRT), cystoid macular edema (CME), and serous retinal detachment (SRD) patterns identified using OCT. Our study encompassed a comprehensive search of PubMed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), and Wan Fang Data from their inception until January 25, 2023. The network meta-analysis involved the inclusion of 1606 patients from 20 retrospective studies with a moderate risk of bias but no evidence of publication bias. The DRT group had the highest increase in best-corrected visual acuity (BCVA) with anti-VEGF, while the SRD group had the greatest reduction in Central Macular Thickness (CMT). Furthermore, conbercept, ranibizumab, and bevacizumab, respectively, showed the best treatment outcomes for patients with DRT, CME, and SRD in terms of improvement in BCVA. And, conbercept exhibited the highest reduction in CMT in the DRT, CME, and SRD groups. In conclusion, our study highlights the efficacy of anti-VEGF agents in the management of DME and provides valuable insights into the selection of anti-VEGF agents tailored to the individual needs of patients.
Topics: Humans; Angiogenesis Inhibitors; Bevacizumab; Diabetic Retinopathy; Intravitreal Injections; Macular Edema; Network Meta-Analysis; Ranibizumab; Receptors, Vascular Endothelial Growth Factor; Recombinant Fusion Proteins; Tomography, Optical Coherence; Treatment Outcome; Vascular Endothelial Growth Factor A; Visual Acuity
PubMed: 38848379
DOI: 10.1371/journal.pone.0304283 -
BMC Cancer Jun 2024Colorectal cancer is the leading cause of cancer death worldwide. The first and second lines of treatment for metastatic colorectal cancer (mCRC) include chemotherapy... (Meta-Analysis)
Meta-Analysis
Colorectal cancer is the leading cause of cancer death worldwide. The first and second lines of treatment for metastatic colorectal cancer (mCRC) include chemotherapy based on 5-fluorouracil. However, treatment following progression on the first and second line is still unclear. We searched PubMed, Scopus, Cochrane, and Web of Science databases for studies investigating the use of trifluridine-tipiracil with bevacizumab versus trifluridine-tipiracil alone for mCRC. We used RStudio version 4.2.3; and we considered p < 0.05 significant. Seven studies and 1,182 patients were included - 602 (51%) received trifluridine-tipiracil plus bevacizumab. Compared with control, the progression-free survival (PFS) (HR 0.52; 95% CI 0.42-0.63; p < 0.001) and overall survival (OS) (HR 0.61; 95% CI 0.52-0.70; p < 0.001) were significantly higher with bevacizumab. The objective response rate (ORR) (RR 3.14; 95% CI 1.51-6.51; p = 0.002) and disease control rate (DCR) (RR 1.66; 95% CI 1.28-2.16; p = 0.0001) favored the intervention. Regarding adverse events, the intervention had a higher rate of neutropenia (RR 1.38; 95% CI 1.19-1.59; p = 0.00001), whereas the monotherapy group had a higher risk of anemia (RR 0.60; 95% CI 0.44-0.82; p = 0.001). Our results support that the addition of bevacizumab is associated with a significant benefit in PFS, OS, ORR and DCR.
Topics: Humans; Colorectal Neoplasms; Bevacizumab; Trifluridine; Thymine; Antineoplastic Combined Chemotherapy Protocols; Pyrrolidines; Drug Combinations; Neoplasm Metastasis; Progression-Free Survival; Uracil; Drug Resistance, Neoplasm
PubMed: 38825703
DOI: 10.1186/s12885-024-12447-8 -
International Journal of Molecular... May 2024Breast cancer, the most invasive cancer in women globally, necessitates novel treatments due to prevailing limitations of therapeutics. Search of news anticancer targets... (Review)
Review
Breast cancer, the most invasive cancer in women globally, necessitates novel treatments due to prevailing limitations of therapeutics. Search of news anticancer targets is more necessary than ever to tackle this pathology. Heat-Shock Protein 90 (HSP90), a chaperone protein, is implicated in breast cancer pathogenesis, rendering it an appealing target. Looking for alternative approach such as Plant-based compounds and natural HSP90 inhibitors offer promising prospects for innovative therapeutic strategies. This study aims to identify plant-based compounds with anticancer effects on breast cancer models and elucidate their mechanism of action in inhibiting the HSP90 protein. A systematic review was conducted and completed in January 2024 and included in vitro, in vivo, and in silico studies that investigated the effectiveness of plant-based HSP90 inhibitors tested on breast cancer models. Eleven studies were included in the review. Six plants and 24 compounds from six different classes were identified and proved to be effective against HSP90 in breast cancer models. The studied plant extracts showed a dose- and time-dependent decrease in cell viability. Variable IC50 values showed antiproliferative effects, with the plant demonstrating the lowest value. Withanolides was the most studied class. Fennel, , and extracts were shown to inhibit tumor growth and angiogenesis and modulate HSP90 expression as well as its cochaperone interactions in breast cancer mouse models. The identified plant extracts and compounds were proven effective against HSP90 in breast cancer models, and this inhibition showed promising effects on breast cancer biology. Collectively, these results urge the need of further studies to better understand the mechanism of action of HSP90 inhibitors using comparable methods for preclinical observations.
Topics: Animals; Female; Humans; Antineoplastic Agents, Phytogenic; Breast Neoplasms; Cell Line, Tumor; Cell Proliferation; Cell Survival; HSP90 Heat-Shock Proteins; Plant Extracts; Neoplasms, Experimental
PubMed: 38791506
DOI: 10.3390/ijms25105468 -
Ophthalmic Research 2024Anti-vascular endothelial growth factor (anti-VEGF) agents have a variable effect on patients with age-related macular degeneration (AMD) that has been attributed to... (Meta-Analysis)
Meta-Analysis Review
Association of the Complement Factor H Y402H Polymorphism and Response to Anti-Vascular Endothelial Growth Factor Treatment in Age-Related Macular Degeneration: An Updated Meta-Analysis.
INTRODUCTION
Anti-vascular endothelial growth factor (anti-VEGF) agents have a variable effect on patients with age-related macular degeneration (AMD) that has been attributed to several causes, including genetic factors. We evaluated the effects of Complement Factor H (CFH) rs1061170/Y402H polymorphism on the response to anti-VEGF therapy among AMD patients.
METHODS
PubMed, Scopus, EMBASE, Web of Science, and Google Scholar were used for a literature search. Pooled odds ratios (ORs) and their 95% confidence intervals (CIs) were estimated to assess the effects of CFH Y402H polymorphism on the response to anti-VEGF therapy in AMD. I2 was used to present the amount of heterogeneity. We used STATA version 14.0 software.
RESULTS
Twenty-five papers reporting data for 4,681 patients were included in this study. Better response to anti-VEGF therapy was seen in T over C (OR = 1.25, 95% CI = 1.04-1.50), TT over CC (OR = 1.60, 95% CI = 1.06-2.4), and TT + TC over CC (OR = 1.68, 95% CI = 1.23-2.28) genotypes. There was no significant difference in the three other genetic models (TT vs. TC, TT vs. TC + CC, TC vs. TT + CC). In Asians, no significant difference was observed in all six genetic models. Ranibizumab and bevacizumab had similar efficacy; however, conbercept was more effective in homozygous genotypes. The literature indicated that TT and TC genotypes and T allele were associated with a better functional response, while the CC genotype and C alleles had a better anatomical response. The combination of risk alleles in ARMS2 A69S (rs10490924), VEGF-A (rs699947), and VEGF-A (rs833069) with Y420H is a predictor of non-respondents.
CONCLUSION
In patients with AMD, the CFH Y402H is a predictor of the response to anti-VEGF agents and should be considered in the treatment plan.
Topics: Humans; Complement Factor H; Vascular Endothelial Growth Factor A; Angiogenesis Inhibitors; Polymorphism, Single Nucleotide; Macular Degeneration; Genotype
PubMed: 38754401
DOI: 10.1159/000539377 -
Drugs May 2024The most recently approved biologics for moderate-to-severe psoriasis are the interleukin (IL)-17 and IL-23 inhibitors. Drug survival is a frequently used outcome to... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND OBJECTIVE
The most recently approved biologics for moderate-to-severe psoriasis are the interleukin (IL)-17 and IL-23 inhibitors. Drug survival is a frequently used outcome to assess drug performance in practice. An overview of the available drug survival studies regarding IL-17 and IL-23 inhibitors is lacking. Therefore, our objective was to assess the drug survival of IL-17 and IL-23 inhibitors for psoriasis.
METHODS
A search of PubMed, Embase, Cochrane Library and Web of Science was conducted (last search 27 December, 2023). Inclusion criteria were (1) cohort study; (2) patients aged ≥ 18 years with plaque psoriasis; and (3) evaluation of drug survival of at least one of the IL-17 and IL-23 inhibitors. Exclusion criteria were: primary focus on patients with psoriatic arthritis, fewer than ten study subjects and another language than English. The Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline was followed. Survival probabilities at monthly intervals were extracted from Kaplan-Meier curves using a semi-automated tool. Data were pooled using a non-parametric random-effects model to retrieve distribution-free summary survival curves. Summary drug survival curves were constructed per biologic for different discontinuation reasons: overall, ineffectiveness and adverse events, and split for the effect modifier biologic naivety. Results were analysed separately for registry/electronic health record data and for pharmacy/claims data.
RESULTS
A total of 69 studies aggregating drug survival outcomes of 48,704 patients on secukinumab, ixekizumab, brodalumab, guselkumab, risankizumab, and tildrakizumab were included. Summary drug survival estimates of registry/electronic health record studies for overall, ineffectiveness and adverse event related drug survival were high (all point estimates ≥ 0.8 at year 1) for included biologics, with highest estimates for guselkumab and risankizumab. All estimates for drug survival were higher in biologic naive than in experienced patients. Estimates of pharmacy/claims databases were substantially lower than estimates from the primary analyses based on registry/electronic health record data.
CONCLUSIONS
This meta-analysis showed that the investigated IL-17 and IL-23 inhibitors had high drug survival rates, with highest rates for guselkumab and risankizumab drug survival. We showed that effect modifiers such as biologic naivety, and the source of data used (registry/electronic health record data vs pharmacy/claims databases) is relevant when interpreting drug survival studies.
Topics: Humans; Psoriasis; Interleukin-17; Interleukin-23; Antibodies, Monoclonal, Humanized; Dermatologic Agents
PubMed: 38630365
DOI: 10.1007/s40265-024-02028-1 -
Journal of Neuro-oncology May 2024Radiation necrosis (RN) is a local inflammatory reaction that arises in response to radiation injury and may cause significant morbidity. This study aims to evaluate and... (Meta-Analysis)
Meta-Analysis Comparative Study Review
PURPOSE
Radiation necrosis (RN) is a local inflammatory reaction that arises in response to radiation injury and may cause significant morbidity. This study aims to evaluate and compare the efficacy of bevacizumab and laser interstitial thermal therapy (LITT) in treating RN in patients with previously radiated central nervous system (CNS) neoplasms.
METHODS
PubMed, Cochrane, Scopus, and EMBASE databases were screened. Studies of patients with radiation necrosis from primary or secondary brain tumors were included. Indirect meta-analysis with random-effect modeling was performed to compare clinical and radiological outcomes.
RESULTS
Twenty-four studies were included with 210 patients in the bevacizumab group and 337 patients in the LITT group. Bevacizumab demonstrated symptomatic improvement/stability in 87.7% of cases, radiological improvement/stability in 86.2%, and steroid wean-off in 45%. LITT exhibited symptomatic improvement/stability in 71.2%, radiological improvement/stability in 64.7%, and steroid wean-off in 62.4%. Comparative analysis revealed statistically significant differences favoring bevacizumab in symptomatic improvement/stability (p = 0.02), while no significant differences were observed in radiological improvement/stability (p = 0.27) or steroid wean-off (p = 0.90). The rates of adverse reactions were 11.2% for bevacizumab and 14.9% for LITT (p = 0.66), with the majority being grade 2 or lower (72.2% for bevacizumab and 62.5% for LITT).
CONCLUSION
Both bevacizumab and LITT exhibited favorable clinical and radiological outcomes in managing RN. Bevacizumab was found to be associated with better symptomatic control compared to LITT. Patient-, diagnosis- and lesion-related factors should be considered when choosing the ideal treatment modality for RN to enhance overall patient outcomes.
Topics: Humans; Bevacizumab; Radiation Injuries; Necrosis; Laser Therapy; Central Nervous System Neoplasms; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors
PubMed: 38619777
DOI: 10.1007/s11060-024-04650-1 -
Advances in Therapy Jun 2024Gastric cancer has the highest incidence and mortality in Eastern Asia. The efficacy and safety of ramucirumab (RAM) monotherapy or in combination with paclitaxel (PTX)... (Review)
Review
Real-World Effectiveness and Safety of Ramucirumab as a Second-Line Treatment for Patients with Unresectable Advanced or Metastatic Gastric/Gastroesophageal Junction Adenocarcinoma in Japan and South Korea: A Systematic Literature Review.
INTRODUCTION
Gastric cancer has the highest incidence and mortality in Eastern Asia. The efficacy and safety of ramucirumab (RAM) monotherapy or in combination with paclitaxel (PTX) for patients with unresectable advanced or metastatic gastric/gastroesophageal junction adenocarcinoma (G/GEA) have been established in clinical trials. To assess the effectiveness and safety of RAM or RAM-based therapy as a second-line treatment in real-world clinical practice in Eastern Asia and to pave the way for future research, a systematic literature review (SLR) was conducted.
METHODS
Studies published between January 2014 and December 2021 were identified in PubMed, Embase, Cochrane Library, CNKI, Wanfang, and CBM databases.
RESULTS
This SLR included 23 studies from Japan and South Korea, of which 22 were retrospective and 11 were full-text articles. Most studies investigated RAM + PTX (range of median overall survival [mOS] 7.4-12.2 months; median progression-free survival [mPFS] 3.35-7.0 months). Data were limited for RAM, RAM + albumin-bound paclitaxel, and RAM + taxane. RAM + PTX was associated with longer survival (mOS 9.3-12.2 months vs. 5.2-9.7 months; mPFS 4.1-5.1 months vs. 3.0-4.1 months) than PTX. Patients with prior anti-programmed cell death 1 (anti-PD-1) exposure experienced longer mPFS (4.8 vs. 3.4 months) from RAM + taxane than those without prior anti-PD-1 exposure. Few patients (3.3-6.3%) discontinued RAM or RAM-based therapy because of adverse events (AEs). Hematological toxicities were most frequently occurring AEs and no new safety signals were identified compared to clinical trials.
CONCLUSION
RAM + PTX as a second-line treatment is effective and associated with an acceptable toxicity profile in patients with advanced or metastatic G/GEA in real-world settings of Japan and South Korea. More studies are recommended to further evaluate effectiveness and safety of RAM or RAM-based therapy, especially after anti-PD-1 therapy, in a wider Eastern Asian population.
TRIAL REGISTRATION
INPLASY registration number INPLASY2022120023.
Topics: Ramucirumab; Humans; Stomach Neoplasms; Antibodies, Monoclonal, Humanized; Adenocarcinoma; Esophagogastric Junction; Republic of Korea; Esophageal Neoplasms; Paclitaxel; Japan; Antineoplastic Combined Chemotherapy Protocols; Treatment Outcome
PubMed: 38619719
DOI: 10.1007/s12325-024-02838-5 -
Journal of Gastrointestinal and Liver... Mar 2024Systemic therapy is mainly recommended for advanced hepatocellular carcinoma (HCC). Considering the variety of treatments available for HCC, there is a need to... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
Systemic therapy is mainly recommended for advanced hepatocellular carcinoma (HCC). Considering the variety of treatments available for HCC, there is a need to understand their relative benefits and risks, especially for the newly approved combination of immune checkpoint inhibitors and vascular endothelial growth factor inhibitors represented by atezolizumab in combination with bevacizumab. A reticulated meta-analysis was used to evaluate the efficacy and safety of atezolizumab-bevacizumab combination therapy compared with other first-line systemic therapies for the treatment of patients advanced HCC.
METHODS
PubMed, The Cochrane Library, Web of Science, and Embase databases were searched from the time of library construction to 01 December 2022, and the data were extracted and analyzed using Stata16.0 for Meta-analysis. The data were extracted separately, and a meta-analysis was performed using the software Stata16.0.
RESULTS
16 clinical studies with 8,779 subjects were identified from 13,417 records and were used to build the evidence network for all trials. TThe combination therapy of atezolizumab and bevacizumab has the advantage of prolonging the OS of patients when treating advanced HCC [HR=5.71, 95%CI (4.30, 7.12), p<0.05] Also, the combination therapy has the advantage of prolonging the patient's progression free survival [HR=1.60, 95%CI (0.89, 2.49), p<0.05].
CONCLUSIONS
Atezolizumab-bevacizumab combination therapy can improve clinical outcomes such as OS and PFS in patients with advanced HCC.
Topics: Humans; Carcinoma, Hepatocellular; Network Meta-Analysis; Bevacizumab; Vascular Endothelial Growth Factor A; Liver Neoplasms
PubMed: 38554414
DOI: 10.15403/jgld-5289