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Hematology (Amsterdam, Netherlands) Dec 2024The treatment landscape of relapsed/refractory multiple myeloma (RRMM) is rapidly evolving in Taiwan. The present study aimed to assess the treatment patterns among RRMM...
BACKGROUND/PURPOSE
The treatment landscape of relapsed/refractory multiple myeloma (RRMM) is rapidly evolving in Taiwan. The present study aimed to assess the treatment patterns among RRMM patients in Taiwan.
METHODS
This retrospective, chart review-based, non-interventional study collected data on RRMM patients (≥20 years old) receiving pomalidomide-based treatment between January 2017 and December 2020 across five sites in Taiwan.
RESULTS
Median age of the study population was 65.6 years. Approximately 75% patients received a doublet regimen and 25% were on a triplet regimen. Disease progression was the most common cause for switching to pomalidomide-based treatments in doublet (71.2%) and triplet (58.3%) groups. Patients in doublet and triplet groups (>80%) received 4 mg pomalidomide as a starting dose. Overall response rate (ORR: 31.5% and 45.8%) and median progression-free survival (PFS: 4.7 and 6.8 months) were reported in the doublet and triplet regimen. Doublet regimen was discontinued mainly due to disease progression or death (78.1%); however, triplet regimen patients mainly terminated their treatment due to reimbursement limitations (29.2%). Healthcare resource utilization (HRU) was comparable between doublet and triplet groups.
CONCLUSION
In Taiwan, half of RRMM patients received pomalidomide-based triplet regimens. Triplet regimens showed a trend towards better outcomes with longer PFS and higher response rates compared to doublets. Notably, the duration of triplet use is influenced by reimbursement limitations. This study provides insight into RRMM treatment patterns in Taiwan and the findings suggest that triplet regimens may be a better alternative than doublet regimens.
Topics: Humans; Multiple Myeloma; Thalidomide; Aged; Female; Male; Taiwan; Retrospective Studies; Middle Aged; Antineoplastic Combined Chemotherapy Protocols; Aged, 80 and over; Adult; Recurrence
PubMed: 38958506
DOI: 10.1080/16078454.2024.2365096 -
The Biochemical Journal Jul 2024Filamin A is an essential protein in the cell cytoskeleton because of its actin binding properties and unique homodimer rod-shaped structure, which organises actin into... (Review)
Review
Filamin A is an essential protein in the cell cytoskeleton because of its actin binding properties and unique homodimer rod-shaped structure, which organises actin into three-dimensional orthogonal networks imperative to cell motility, spreading and adhesion. Filamin A is subject to extensive posttranslational modification (PTM) which serves to co-ordinate cellular architecture and to modulate its large protein-protein interaction network which is key to the protein's role as a cellular signalling hub. Characterised PTMs include phosphorylation, irreversible cleavage, ubiquitin mediated degradation, hydroxylation and O-GlcNAcylation, with preliminary evidence of tyrosylation, carbonylation and acetylation. Each modification and its relation to filamin A function will be described here. These modifications are often aberrantly applied in a range of diseases including, but not limited to, cancer, cardiovascular disease and neurological disease and we discuss the concept of target specific PTMs with novel therapeutic modalities. In summary, our review represents a topical 'one-stop-shop' that enables understanding of filamin A function in cell homeostasis and provides insight into how a variety of modifications add an extra level of Filamin A control.
Topics: Filamins; Humans; Protein Processing, Post-Translational; Animals; Phosphorylation; Neoplasms
PubMed: 38958472
DOI: 10.1042/BCJ20240121 -
Blood Jul 2024Myelodysplastic syndromes/neoplasms (MDS) are clonal hematologic disorders characterized by morphologic abnormalities of myeloid cells and peripheral cytopenias. While...
Myelodysplastic syndromes/neoplasms (MDS) are clonal hematologic disorders characterized by morphologic abnormalities of myeloid cells and peripheral cytopenias. While genetic abnormalities underlie the pathogenesis of these disorders and their heterogeneity, current classifications of MDS rely predominantly on morphology. We performed genomic profiling of 3,233 patients with MDS or related disorders to delineate molecular subtypes and define their clinical implications. Gene mutations, copy-number alterations (CNAs), and copy-neutral loss of heterozygosity (cnLOH) were derived from targeted sequencing of a 152-gene panel, with abnormalities identified in 91, 43, and 11% of patients, respectively. We characterized 16 molecular groups, encompassing 86% of patients, using information from 21 genes, 6 cytogenetic events, and LOH at the TP53 and TET2 loci. Two residual groups defined by negative findings (molecularly not-otherwise specified, absence of recurrent drivers) comprised 14% of patients. The groups varied in size from 0.5% to 14% of patients and were associated with distinct clinical phenotypes and outcomes. The median bone marrow blast percentage across groups ranged from 1.5 to 10%, and the median overall survival from 0.9 to 8.2 years. We validated 5 well-characterized entities, added further evidence to support 3 previously reported subsets, and described 8 novel groups. The prognostic influence of bone marrow blasts depended on the genetic subtypes. Within genetic subgroups, therapy-related MDS and myelodysplastic/myeloproliferative neoplasms (MDS/MPN) had comparable clinical and outcome profiles to primary MDS. In conclusion, genetically-derived subgroups of MDS are clinically relevant and may inform future classification schemas and translational therapeutic research.
PubMed: 38958467
DOI: 10.1182/blood.2023023727 -
Head & Neck Jul 2024
PubMed: 38958400
DOI: 10.1002/hed.27852 -
Head & Neck Jul 2024
PubMed: 38958384
DOI: 10.1002/hed.27853 -
Brazilian Journal of Medical and... 2024The overexpression of P-glycoprotein (P-gp/ABCB1) is a leading cause of multidrug resistance (MDR). Hence, it is crucial to discover effective pharmaceuticals that...
The overexpression of P-glycoprotein (P-gp/ABCB1) is a leading cause of multidrug resistance (MDR). Hence, it is crucial to discover effective pharmaceuticals that counteract ABCB1-mediated multidrug resistance. FRAX486 is a p21-activated kinase (PAK) inhibitor. The objective of this study was to investigate whether FRAX486 can reverse ABCB1-mediated multidrug resistance, while also exploring its mechanism of action. The CCK8 assay demonstrated that FRAX486 significantly reversed ABCB1-mediated multidrug resistance. Furthermore, western blotting and immunofluorescence experiments revealed that FRAX486 had no impact on expression level and intracellular localization of ABCB1. Notably, FRAX486 was found to enhance intracellular drug accumulation and reduce efflux, resulting in the reversal of multidrug resistance. Docking analysis also indicated a strong affinity between FRAX486 and ABCB1. This study highlights the ability of FRAX486 to reverse ABCB1-mediated multidrug resistance and provides valuable insights for its clinical application.
Topics: Humans; Drug Resistance, Neoplasm; Breast Neoplasms; ATP Binding Cassette Transporter, Subfamily B; Drug Resistance, Multiple; Female; p21-Activated Kinases; Cell Line, Tumor; Blotting, Western
PubMed: 38958364
DOI: 10.1590/1414-431X2024e13357 -
Brazilian Journal of Medical and... 2024Arbutin is utilized in traditional remedies to cure numerous syndromes because of its anti-microbial, antioxidant, and anti-inflammatory properties. This study aimed to...
Arbutin is utilized in traditional remedies to cure numerous syndromes because of its anti-microbial, antioxidant, and anti-inflammatory properties. This study aimed to evaluate chemopreventive effects of arbutin on azoxymethane (AOM)-induced colon aberrant crypt foci (ACF) in rats. Five groups of rats were used: normal control group (rats injected hypodermically with sterile phosphate-buffered saline once per week for two weeks) and groups 2-5, which were subcutaneously inoculated with 15 mg/kg AOM once a week for two weeks. AOM control and 5-fluorouracil (5-FU) control groups were fed 10% Tween orally daily for 8 weeks using a feeding tube. The treated groups were fed 30 and 60 mg/kg arbutin every day for 2 months. ACF from the AOM control group had aberrant nuclei in addition to multilayered cells and an absence of goblet cells. The negative control group displayed spherical cells and nuclei in basal positions. Histological examination revealed a reduced number of AFC cells from colon tissues of the 5-FU reference group. Arbutin-fed animals showed down-regulation of proliferating cell nuclear antigen (PCNA) and up-regulation of Bax protein compared to AOM control. Rats fed with arbutin displayed a significant increase of superoxide dismutase (SOD) and catalase (CAT) activities in colon tissue homogenates compared to the AOM control group. In conclusion, arbutin showed therapeutic effects against colorectal cancer, explained by its ability to significantly decrease ACF, down-regulate PCNA protein, and up-regulate Bax protein. In addition, arbutin significantly increased SOD and CAT, and decreased malondialdehyde (MDA) levels, which might be due to its anti-proliferative and antioxidant properties.
Topics: Animals; Azoxymethane; Aberrant Crypt Foci; Proliferating Cell Nuclear Antigen; Male; Arbutin; Rats; bcl-2-Associated X Protein; Colon; Rats, Wistar; Fluorouracil; Carcinogens
PubMed: 38958363
DOI: 10.1590/1414-431X2024e13306 -
Arquivos Brasileiros de Cirurgia... 2024The present manuscript aimed to review the historical development and most important contributions regarding Lynch Syndrome since its first description, more than a... (Review)
Review
The present manuscript aimed to review the historical development and most important contributions regarding Lynch Syndrome since its first description, more than a century ago. In 1895, a reputed pathologist from Michigan University, Dr. Aldred Scott Warthin, got intrigued by the family history of a local seamstress called Pauline Gross. According to her prevision, she would present an early death due to cancer, which actually happened (from the uterus). Historically, her family was designated "Family G", comprising a group recognized as the longest and most detailed cancer genealogy that has ever been studied. Warthin concluded that its members had genetic susceptibility for cancer, and they are, nowadays, considered the first reported Lynch Syndrome family. At that time, however, the medical cancer community was far less receptive to the association between heredity and cancer, despite the description of other families with similar heredograms. Unfortunately, this historical fact remained somewhat dormant until another investigator inaugurated a new era in the understanding of family cancer clusters. After reports and studies from this family and many others, the condition initially called Cancer Family Syndrome was changed to the eponym Lynch Syndrome. This was a recognition of the extensive and dedicated work developed by Dr. Henry Lynch in describing various characteristics of the disease, and his efforts to establish the correct recommendations for its diagnosis and treatment. Although the future announces there is still far to go for a complete understanding of Lynch Syndrome, the remarkable contributions of Pauline's intuition, Warthin's perseverance, and Lynch's work consistency must never be forgotten by those who already have or will still benefit from this knowledge.
Topics: History, 20th Century; Colorectal Neoplasms, Hereditary Nonpolyposis; History, 19th Century; Humans; Colorectal Neoplasms
PubMed: 38958348
DOI: 10.1590/0102-6720202400019e1812 -
Arquivos Brasileiros de Cirurgia... 2024Molecular medicine opened new horizons in understanding disease mechanisms and discovering target interventions. The wider availability of DNA and RNA sequencing,... (Review)
Review
Molecular medicine opened new horizons in understanding disease mechanisms and discovering target interventions. The wider availability of DNA and RNA sequencing, immunohistochemical analysis, proteomics, and other molecular tests changed how physicians manage diseases. The gastric cancer molecular classification proposed by The Cancer Genome Atlas Program divides gastric adenocarcinomas into four subtypes. However, the available targets and/or immunotherapies approved for clinical use seem to be dissociated from these molecular subtypes. Until a more reliable interpretation of the stupendous amount of data provided by the molecular classifications is presented, the clinical guidelines will rely on available actionable targets and approved therapies to guide clinicians in conducting cancer management in the era of molecular therapies.
Topics: Stomach Neoplasms; Humans; Adenocarcinoma; Molecular Targeted Therapy
PubMed: 38958347
DOI: 10.1590/0102-6720202400018e1811 -
Arquivos Brasileiros de Cirurgia... 2024Despite the preference for multimodal treatment for gastric cancer, abandonment of chemotherapy treatment as well as the need for upfront surgery in obstructed patients...
PERIOPERATIVE CHEMOTHERAPY, ADJUVANT CHEMOTHERAPY AND ADJUVANT CHEMORADIOTHERAPY IN THE SURGICAL TREATMENT OF GASTRIC CANCER IN A HOSPITAL OF THE BRAZILIAN UNIFIED HEALTH SYSTEM.
BACKGROUND
Despite the preference for multimodal treatment for gastric cancer, abandonment of chemotherapy treatment as well as the need for upfront surgery in obstructed patients brings negative impacts on the treatment. The difficulty of accessing treatment in specialized centers in the Brazilian Unified National Health System (SUS) scenario is an aggravating factor.
AIMS
To identify advantages, prognostic factors, complications, and neoadjuvant and adjuvant therapies survival in gastric cancer treatment in SUS setting.
METHODS
The retrospective study included 81 patients with gastric adenocarcinoma who underwent treatment according to INT0116 trial (adjuvant chemoradiotherapy), CLASSIC trial (adjuvant chemotherapy), FLOT4-AIO trial (perioperative chemotherapy), and surgery with curative intention (R0 resection and D2 lymphadenectomy) in a single cancer center between 2015 and 2020. Individuals with other histological types, gastric stump, esophageal cancer, other treatment protocols, and stage Ia or IV were excluded.
RESULTS
Patients were grouped into FLOT4-AIO (26 patients), CLASSIC (25 patients), and INT0116 (30 patients). The average age was 61 years old. More than 60% of patients had pathological stage III. The treatment completion rate was 56%. The pathological complete response rate of the FLOT4-AIO group was 7.7%. Among the prognostic factors that impacted overall survival and disease-free survival were alcoholism, early postoperative complications, and anatomopathological status pN2 and pN3. The 3-year overall survival rate was 64.9%, with the CLASSIC subgroup having the best survival (79.8%).
CONCLUSIONS
The treatment strategy for gastric cancer varies according to the need for initial surgery. The CLASSIC subgroup had better overall survival and disease-free survival. The INT0116 regimen also protected against mortality, but not with statistical significance. Although FLOT4-AIO is the preferred treatment, the difficulty in carrying out neoadjuvant treatment in SUS scenario had a negative impact on the results due to the criticality of food intake and worse treatment tolerance.
Topics: Humans; Stomach Neoplasms; Middle Aged; Male; Female; Chemotherapy, Adjuvant; Retrospective Studies; Brazil; Aged; Chemoradiotherapy, Adjuvant; Adenocarcinoma; Adult; Prognosis; National Health Programs; Gastrectomy; Neoadjuvant Therapy; Treatment Outcome; Neoplasm Staging; Perioperative Care
PubMed: 38958346
DOI: 10.1590/0102-6720202400017e1810