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Future Oncology (London, England) Jun 2023A meta-analysis was conducted to systematically review the risks of all-grade as well as high-grade rash in chronic myelogenous leukemia (CML) patients using... (Meta-Analysis)
Meta-Analysis Review
A meta-analysis was conducted to systematically review the risks of all-grade as well as high-grade rash in chronic myelogenous leukemia (CML) patients using different types of BCR-ABL inhibitors. Literature published between 2000 and April 2022 were searched using PubMed, Cochrane Library, Embase and ClinicalTrials.gov. A total of 12 studies were included for meta-analysis. The results showed that the incidence of all-grade or high-grade rash associated with new-generation BCR-ABL inhibitors had no significant difference compared with a standard dose of imatinib. Subgroup analysis suggested that, compared with imatinib, the incidence of all grades of rash was higher in the nilotinib, bosutinib and ponatinib groups. For CML patients treated with nilotinib, bosutinib and ponatinib, the occurrence of skin toxicity should not be ignored.
Topics: Humans; Imatinib Mesylate; Fusion Proteins, bcr-abl; Protein Kinase Inhibitors; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Exanthema; Antineoplastic Agents; Drug Resistance, Neoplasm
PubMed: 37368411
DOI: 10.2217/fon-2022-1008 -
Phytomedicine : International Journal... Dec 2022Eugenol (1-allyl-4-hydroxy-3-methoxybenzene) is an important simple phenolic compound mainly derived from Syzygium aromaticum and many other plants. It is traditionally... (Review)
Review
BACKGROUND
Eugenol (1-allyl-4-hydroxy-3-methoxybenzene) is an important simple phenolic compound mainly derived from Syzygium aromaticum and many other plants. It is traditionally used in ayurveda and aromatherapy for the healing of many health problems. It also has significant applications in dentistry, agriculture, and flavour industry. This simple phenol has an eclectic range of pharmacological properties, such as antioxidant, anti-inflammatory, and anticancer activities. It is regarded as safe by the Food and Agricultural Organization of the United Nations due to its non-carcinogenic and non-mutagenic properties.
PURPOSE
The aim of this comprehensive review is to present a critical and systematic assessment of the antitumor ability of eugenol and its associated molecular targets in various cancers.
METHODS
It was carried out following the preferred reporting items for systematic reviews and meta-analysis guidelines. Risk of bias assessment was performed using the SYstematic review centre for laboratory animal experimentation guidelines. The literature search was performed in standard databases such as Science Direct, PubMed, Google Scholar, Scopus, and Web of Science using the keywords 'eugenol' or 'eugenol essential oil' and 'anti-cancer properties of eugenol'.
RESULTS
The scientific information from fifty-three studies was encompassed in the present review work. Eugenol exhibits significant anticancer effects in a variety of biological pathways, namely apoptosis, autophagy, cell cycle progression, inflammation, invasion, and metastasis. Eugenol-induced apoptosis has been noticed in osteosarcoma, skin tumors, melanoma, leukemia, gastric and mast cells. It decreases the expression of cyclin D1, cyclin B, proliferating cell nuclear antigen, nuclear factor-ƙB, inhibitor of nuclear factor ƙB, and B-cell lymphoma-2. Eugenol increases the expression of B-cell lymphoma-2 (BCL-2) associated X, BH3-interacting domain death agonist, BCL-2 associated agonist of cell death, apoptotic protease activating factor 1, cytochrome c, p21, and p53.
CONCLUSION
The anticancer potential exhibited by eugenol is mainly attributed to its anti-metastatic, anti-proliferative, anti-angiogenic, anti-inflammatory, cell cycle arrest, apoptotic, and autophagic effects. Hence, the use of eugenol alone or along with other chemotherapeutic anticancer agents is found to be very effective in cancer therapy.
Topics: Animals; Anti-Inflammatory Agents; Antineoplastic Agents; Antioxidants; Apoptotic Protease-Activating Factor 1; Cyclin B; Cyclin D1; Cytochromes c; Eugenol; Neoplasms; Oils, Volatile; Phenols; Proliferating Cell Nuclear Antigen; Proto-Oncogene Proteins c-bcl-2; Tumor Suppressor Protein p53
PubMed: 36152592
DOI: 10.1016/j.phymed.2022.154456 -
Journal of Molecular Neuroscience : MN Nov 2020Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder and is characterized by degeneration and axon loss from the upper motor neuron, that descends from... (Review)
Review
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder and is characterized by degeneration and axon loss from the upper motor neuron, that descends from the lower motor neuron in the brain. Over the period, assorted outcomes from medical findings, molecular pathogenesis, and structural and biophysical studies have abetted in providing thoughtful insights underlying the importance of disease-causing genes in ALS. Consequently, numerous mechanisms were proposed for the pathogenesis of ALS, considering protein mutations, aggregation, and misfolding. Besides, the answers to the majority of ALS cases that happen to be sporadic still remain obscure. The application in discovering susceptibility factors in ALS contemplating the genetic factors is to be further dissevered in the future years with innovation in research studies. Hence, this review targets in revisiting the breakthroughs on the disease-causing genes related with ALS.
Topics: Amyotrophic Lateral Sclerosis; Animals; C9orf72 Protein; Genetic Predisposition to Disease; Humans; Profilins; RNA-Binding Protein FUS; Superoxide Dismutase-1
PubMed: 32415434
DOI: 10.1007/s12031-020-01569-w -
Breast (Edinburgh, Scotland) Jun 2023Patients with HER2+ breast cancer (BC) frequently develop leptomeningeal metastases (LM). While HER2-targeted therapies have demonstrated efficacy in the neoadjuvant,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Patients with HER2+ breast cancer (BC) frequently develop leptomeningeal metastases (LM). While HER2-targeted therapies have demonstrated efficacy in the neoadjuvant, adjuvant, and metastatic settings, including for parenchymal brain metastases, their efficacy for patients with LM has not been studied in a randomized controlled trial. However, several single-armed prospective studies, case series and case reports have studied oral, intravenous, or intrathecally administered HER2-targeted therapy regimens for patients with HER2+ BC LM.
METHODS
We conducted a systematic review and meta-analysis of individual patient data to evaluate the efficacy of HER2-targeted therapies in HER2+ BC LM in accordance with PRISMA guidelines. Targeted therapies evaluated were trastuzumab (intrathecal or intravenous), pertuzumab, lapatinib, neratinib, tucatinib, trastuzumab-emtansine and trastuzumab-deruxtecan. The primary endpoint was overall survival (OS), with CNS-specific progression-free survival (PFS) as a secondary endpoint.
RESULTS
7780 abstracts were screened, identifying 45 publications with 208 patients, corresponding to 275 lines of HER2-targeted therapy for BC LM which met inclusion criteria. In univariable and multivariable analyses, we observed no significant difference in OS and CNS-specific PFS between intrathecal trastuzumab compared to oral or intravenous administration of HER2-targeted therapy. Anti-HER2 monoclonal antibody-based regimens did not demonstrate superiority over HER2 tyrosine kinase inhibitors. In a cohort of 15 patients, treatment with trastuzumab-deruxtecan was associated with prolonged OS compared to other HER2-targeted therapies and compared to trastuzumab-emtansine.
CONCLUSIONS
The results of this meta-analysis, comprising the limited data available, suggest that intrathecal administration of HER2-targeted therapy for patients with HER2+ BC LM confers no additional benefit over oral and/or IV treatment regimens. Although the number of patients receiving trastuzumab deruxtecan in this cohort is small, this novel agent offers promise for this patient population and requires further investigation in prospective studies.
Topics: Female; Humans; Ado-Trastuzumab Emtansine; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Prospective Studies; Randomized Controlled Trials as Topic; Receptor, ErbB-2; Trastuzumab; Meningeal Neoplasms
PubMed: 37156650
DOI: 10.1016/j.breast.2023.04.008 -
Cancer Treatment Reviews Jan 2023ERBB2 amplification is a driver oncogenic alteration in many cancers and it has recently been incorporated among therapeutically actionable biomarkers also in metastatic... (Review)
Review
ERBB2 amplification is a driver oncogenic alteration in many cancers and it has recently been incorporated among therapeutically actionable biomarkers also in metastatic colorectal cancer (mCRC). In contrast, the role of ERBB2 point mutations, which are detectable in up to 3% of CRC patients, remains to be assessed. In this systematic review, we collected preclinical and clinical data addressing the role of ERBB2 point mutations in mCRC patients as a predictive biomarker for anti-EGFR and anti-HER2 targeted agents, and as mechanism of acquired resistance to ERBB2 amplified mCRC treated with any anti-HER2 regimen. In both preclinical and clinical studies, most ERBB2 point mutations were associated with resistance to anti-EGFR agents, particularly L755S and R784G, which occur in the HER2 protein kinase domain. No ERBB2 mutation was associated with tumor response to HER2-targeted agents in mCRC patients, although signals of activity were observed in preclinical models. Eight ongoing clinical trials are underway to test different anti-HER2 treatments in ERBB2 mutant mCRC. Several reports documented the emergence of ERBB2 mutations in the circulating tumor DNA (ctDNA) of ERBB2 amplified mCRC progressing to anti-HER2 agents, thus hinting a role in acquired resistance.
Topics: Humans; Point Mutation; Colorectal Neoplasms; Receptor, ErbB-2; Antineoplastic Agents; Colonic Neoplasms; Mutation; Rectal Neoplasms; Biomarkers, Tumor
PubMed: 36410093
DOI: 10.1016/j.ctrv.2022.102488 -
Biochimica Et Biophysica Acta. Reviews... Nov 2023This study aimed to explore the efficacy and safety of trastuzumab plus tyrosine kinase inhibitors (TKIs) compared with those of trastuzumab monotherapy in patients with... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This study aimed to explore the efficacy and safety of trastuzumab plus tyrosine kinase inhibitors (TKIs) compared with those of trastuzumab monotherapy in patients with human epidermal growth factor receptor (HER2)-positive breast cancer.
METHODS
The PubMed, Embase, Cochrane, and Web of Science databases were systematically searched for relevant articles from inception until September 2022. The primary outcomes were overall survival (OS) and progression-free survival (PFS). Subgroup analyses were performed based on disease status, TKI type, and hormone receptor status.
RESULTS
Sixteen studies were included in the current analysis. Trastuzumab plus TKI significantly improved OS and PFS compared to trastuzumab monotherapy. In the neoadjuvant setting, trastuzumab plus TKI significantly increased the pathologic complete response (pCR) rate compared to trastuzumab monotherapy. Moreover, a higher objective response rate (ORR) was observed with trastuzumab plus TKI. Patients who received the combination therapy had a higher incidence of discontinuation, all-grade diarrhea, and grade ≥ 3 diarrhea.
CONCLUSIONS
Trastuzumab plus TKI was better than trastuzumab monotherapy for treating different stages of HER2-positive breast cancer. The safety of trastuzumab plus TKI anti-HER2 therapy was controllable. The different efficacies of TKIs combined with trastuzumab may be related to the mechanism of action of the different TKIs, needing further investigations.
Topics: Humans; Female; Trastuzumab; Breast Neoplasms; Tyrosine Kinase Inhibitors; Receptor, ErbB-2; Protein Kinase Inhibitors; Diarrhea
PubMed: 37640146
DOI: 10.1016/j.bbcan.2023.188969 -
Clinical and Experimental Medicine Nov 2023Anti-human epidermal growth factor receptor-2 (anti-HER2) therapy has shown excellent efficacy in patients with HER2 overexpression and amplification. Although HER2... (Meta-Analysis)
Meta-Analysis Review
Anti-human epidermal growth factor receptor-2 (anti-HER2) therapy has shown excellent efficacy in patients with HER2 overexpression and amplification. Although HER2 mutations are rarely expressed in several cancers, when they occur, they can activate the HER2 signaling pathway. In recent years, studies have shown that anti-HER2 drugs have promising efficacy in patients with HER2 mutations. Based on keywords, we searched databases, such as PubMed, Embase, and Cochrane Library, and the main conference abstracts. We extracted data on objective response rate (ORR), clinical benefit rate (CBR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS) from studies on the efficacy of anti-HER2 therapies in patients with HER2-mutated cancers, and analyzed grade 3 or higher adverse events (AEs). We included 19 single-arm clinical studies and 3 randomized controlled trials (RCTs), containing a total of 1017 patients with HER2 mutations, involving seven drugs and nine cancers, and 18 studies enrolled a high proportion of heavily pretreated patients who had received multiple lines of therapy. Our results showed pooled ORR and CBR of 25.0% (range, 3.8-72.7%; 95% CI, 18-32%) and 36.0% (range, 8.3-63.0%; 95% CI, 31-42%) for anti-HER2 therapy in HER2-mutated cancers. The pooled median PFS, OS, DOR were 4.89 (95% CI, 4.16-5.62), 12.78 (95% CI, 10.24-15.32), and 8.12 (95% CI, 6.48-9.75) months, respectively. In a subgroup analysis, we analyzed the ORR for different cancers, showing 27.0, 25.0, 23.0, and 16.0% for breast, lung, cervical, and biliary tract cancers, respectively. ORR analyses were performed for different drugs as monotherapy or in combination, showing 60.0% for trastuzumab deruxtecan (T-DXd), 31.0% for pyrotinib, 26.0% for neratinib combined with trastuzumab, 25.0% for neratinib combined with fulvestrant, 19.0% for trastuzumab combined with pertuzumab, and 16.0% for neratinib. In addition, we found that diarrhoea, neutropenia, and thrombocytopenia were the most common grade ≥ 3 AEs associated with anti-HER2 therapeutic agents. In this meta-analysis of heavily pretreated patients with HER2 mutations, anti-HER2 therapies, DS-8201 and trastuzumab emtansine, showed promising efficacy and activity. Anti-HER2 therapies showed different efficacies in different or the same cancer settings and all had a tolerable safety profile.
Topics: Humans; Female; Trastuzumab; Receptor, ErbB-2; Ado-Trastuzumab Emtansine; Neoplasms; Breast Neoplasms; Antineoplastic Combined Chemotherapy Protocols
PubMed: 37120775
DOI: 10.1007/s10238-023-01072-7 -
Cancer Treatment Reviews Apr 2023The prognostic differences between HER2-zero and HER2-low breast cancer (BC) remain unclear. Purpose of this meta-analysis is to investigate the differences between... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The prognostic differences between HER2-zero and HER2-low breast cancer (BC) remain unclear. Purpose of this meta-analysis is to investigate the differences between HER2-low and HER2-zero in terms of clinicopathological factors and survival outcomes in early-stage BC.
METHODS
We searched major databases and congress proceedings until November 1, 2022 to identify studies comparing HER2-zero and HER2-low in early-stage BC. HER2-zero immunohistochemically (IHC) was defined as score 0, while HER2-low was defined as IHC 1+ or 2+/in situ hybridization negative.
RESULT
A total of 23 retrospective studies involving 636,535 patients were included. HER2-low rate was 67.5% in the hormone receptor (HR)-positive group, while this rate was 48.6% in the HR-negative group. In the analysis of clinicopathological factors by HR status, the proportion of premenopausal patients within the HR-positive group was greater in the HER2-zero arm (66.5% vs 61.8%), whereas grade 3 tumors (74.2% vs 71.5%), patients younger than 50 years of age (47.3% vs 39.6%), and T3-T4 tumors (7.7% vs 6.3%) within the HR-negative group was higher in the HER2-zero arm. In both the HR-positive and HR-negative groups, the HER2-low arm showed significantly improved results for disease-free survival (DFS) and overall survival (OS). The hazard ratios for DFS and OS in the HR-positive group were 0.88 (95% CI 0.83-0.94) and 0.87 (95% CI 0.78-0.96), respectively. In the HR-negative group, the hazard ratios for DFS and OS were 0.87 (95% CI 0.79-0.97) and 0.86 (95% CI 0.84-0.89), respectively.
CONCLUSION
In early-stage BC, HER2-low is associated with better DFS and OS compared to HER2-zero, regardless of HR status.
Topics: Humans; Female; Breast Neoplasms; Retrospective Studies; Prognosis; Proportional Hazards Models; Disease-Free Survival; Receptor, ErbB-2
PubMed: 36898351
DOI: 10.1016/j.ctrv.2023.102538 -
Human Cell Mar 2022The Proviral Integration of Molony murine leukemia virus (PIM)-1 protein contributes to the solid cancers and hematologic malignancies, cell growth, proliferation,... (Review)
Review
The Proviral Integration of Molony murine leukemia virus (PIM)-1 protein contributes to the solid cancers and hematologic malignancies, cell growth, proliferation, differentiation, migration, and other life activities. Many studies have related these functions to its molecular structure, subcellular localization and expression level. However, recognition of specific active sites and their effects on the activity of this constitutively active kinase is still a challenge. Based on the close relationship between its molecular structure and functional activity, this review covers the specific residues involved in the binding of ATP and different substrates in its catalytic domain. This review then elaborates on the relevant changes in protein conformation and cell functions after PIM-1 binds to different substrates. Therefore, this intensive study can improve the understanding of PIM-1-regulated signaling pathways by facilitating the discovery of its potential phosphorylation substrates.
Topics: Animals; Catalytic Domain; Cell Proliferation; Hematologic Neoplasms; Mice; Phosphorylation; Protein Kinase Inhibitors; Proto-Oncogene Proteins c-pim-1
PubMed: 35000143
DOI: 10.1007/s13577-021-00656-3 -
British Journal of Cancer Mar 2024Cervical carcinogenesis is mediated by the HPV-E6 and E7 oncoproteins, considered as biomarkers usable in managing screen-positive women. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cervical carcinogenesis is mediated by the HPV-E6 and E7 oncoproteins, considered as biomarkers usable in managing screen-positive women.
METHODS
We conducted a systematic review and meta-analysis assessing the accuracy of HPV-E6/E7-oncoprotein tests to detect underlying cervical-precancer and cancer. We included studies reporting data on oncoprotein test accuracy detecting cervical intraepithelial neoplasia grade 3 or worse. Random effects logistic regression models were applied for pooling absolute and relative accuracy.
RESULTS
Twenty-two studies were included. Sensitivity and specificity estimates ranged from 54.2% (95%CI: 45.2-63.0) to 69.5% (95%CI:60.8-76.9) and from 82.8% (95%CI: 50.4-95.8) to 99.1 (95%CI: 98.8-99.3), respectively in the population irrespective of HPV status. Higher sensitivity estimates ranging from 60.8% (95%CI: 49.6-70.9) to 75.5% (95%CI: 71.7-78.9) but lower specificity estimates ranging from 83.7% (95%CI: 76.1-89.3) to 92.1% (95%CI: 88.5-94.6) were observed in studies enrolling high-risk-HPV-positive women. Studies recruiting only HIV-positive women showed a pooled sensitivity of 46.9% (95%CI: 30.6-63.9) with a specificity of 98.0% (95%CI: 96.8-98.7).
CONCLUSIONS
The high specificity of oncoprotein tests supports its use for triaging HPV-positive women. However, oncoprotein-negative women would not be recommended to undertake routine screening, requiring further follow-up. Large-scale and longitudinal studies are needed to further investigate the role of E6/E7-oncoprotein detection in predicting the risk of developing cervical pre-cancer and cancer.
Topics: Female; Humans; Papillomavirus Infections; Uterine Cervical Dysplasia; Oncogene Proteins, Viral; Cervix Uteri; Papillomavirus E7 Proteins; Uterine Cervical Neoplasms; Papillomaviridae
PubMed: 37973957
DOI: 10.1038/s41416-023-02490-w