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Critical Reviews in Oncology/hematology Jun 2024This systematic review aimed to update the perceived needs of individuals with breast cancer (BC). Databases were searched for studies reporting quantitative data... (Review)
Review
This systematic review aimed to update the perceived needs of individuals with breast cancer (BC). Databases were searched for studies reporting quantitative data collected through validated assessment tools. Needs of adults with BC were reported by survivorship phase. The post-diagnosis and the post-surgery phases revealed the most needs; health system and information needs represented the greatest concern, with average Supportive Care Needs Survey-Short Form (SCNS-SF34) scores ranging from 62.0 to 75.8 post-diagnosis and from 45.0 to 67.8 post-surgery. Needs then seemed to decrease or remain stable up to within one year from diagnosis, when needs in all domains increased again; health system and information needs remained a priority. Younger age, side effects, type of treatment, and advanced stage were associated with the occurence of unmet needs. The needs of BC survivors vary over the course of their cancer experience. This knowledge can assist the planning of appropriate assessments.
PubMed: 38955309
DOI: 10.1016/j.critrevonc.2024.104432 -
Endoscopy Jul 2024Adenoma surveillance guidelines are based on non-fecal immunochemical test (FIT)-based screening settings. However, colorectal cancer (CRC) risk may be different in...
Detection of colorectal cancer and advanced neoplasia during first surveillance interval after detection of adenomas in fecal immunochemical test cancer screening: a nationwide study.
BACKGROUND
Adenoma surveillance guidelines are based on non-fecal immunochemical test (FIT)-based screening settings. However, colorectal cancer (CRC) risk may be different in FIT-positive screening populations. We evaluated the CRC and advanced adenoma risk within the recommended surveillance periods in the Danish FIT-based CRC screening program for participants with intermediate or high risk adenomas according to 2010 European guidelines. Furthermore, we estimated CRC risk for those who were not recommended surveillance according to European Society of Gastrointestinal Endoscopy (ESGE) 2020 guidelines.
METHODS
Using nationwide health registries, we identified 17 936 FIT-screening participants from 2014-2017 with adenomas undergoing surveillance (high risk 1 year, intermediate risk 3 years). Participants with a follow-up examination were included (N = 10 068). Relative risk (RR) of CRC and advance adenoma was compared between intermediate and high risk groups and between intermediates who were recommended surveillance (S) or no surveillance (NS) according to 2020 ESGE guidelines.
RESULTS
During surveillance, CRC occurred in 0.59% of the high risk group and 1.11% of the intermediate risk group (RR 0.53 [95%CI 0.34-0.84]). The high risk group had a 24% increased risk of advanced adenoma. CRC occurred in 1.69% of the intermediateNS group and 0.87% of the intermediateS group (RR 1.94 [95%CI 1.18-3.21]), and RR for advanced adenoma was 1.19 (95%CI 1.03-1.37).
CONCLUSION
CRC detection was lower among participants rated at higher risk at initial CRC screening. Findings at first screen-derived colonoscopy might not be as good a predictor of CRC risk in a FIT-positive screening population.
PubMed: 38955210
DOI: 10.1055/a-2343-5700 -
Pharmacology Jul 2024Kidney cancer ranks as the ninth most common cancer in men and the fourteenth in women globally, with renal cell carcinoma (RCC) being the most prevalent type. Despite...
INTRODUCTION
Kidney cancer ranks as the ninth most common cancer in men and the fourteenth in women globally, with renal cell carcinoma (RCC) being the most prevalent type. Despite advances in therapeutic strategies targeting angiogenesis and immune checkpoints, the absence of reliable markers for patient selection and limited duration of disease control underline the need for innovative approaches. CK1δ and CK1ε are highly conserved serine/threonine kinases involved in cell cycle regulation, apoptosis, and circadian rhythm. While CK1δ dysregulation is reportedly associated with breast and bladder cancer progression, their role in RCC remains elusive. This study aims to investigate the feasibility of CK1δ/ε as new therapeutic targets for RCC patients.
METHODS
The relationship between CK1δ/ε and RCC progression was evaluated by the analysis of microarray dataset and TCGA database. The anticancer activity of CK1δ/ε inhibitor was examined by MTT/SRB assay , and apoptotic cell death was analyzed by flow cytometry and western blotting.
RESULTS
Our data demonstrate that the gene expression of CSNK1D and CSNK1E is significantly higher in clear cell RCC (ccRCC) tissues compared to normal kidney samples, which is correlated with lower survival rates in ccRCC patients. SR3029, a selective inhibitor targeting CK1δ/ε, significantly suppresses the viability and proliferation of ccRCC cell lines regardless of the status of VHL deficiency. Importantly, the inhibitor promotes the population of subG1 cells and induces apoptosis, and ectopically expression of CK1δ partially rescued SR3029-induced apoptosis in ccRCC cells.
CONCLUSION
These findings underscore the crucial role of CK1δ and CK1ε in ccRCC progression, suggesting CK1δ/ε inhibitors as new therapeutic options for ccRCC patients.
PubMed: 38955142
DOI: 10.1159/000540182 -
Redox Biology Jun 2024Ferroptosis is a form of iron-related oxidative cell death governed by an integrated redox system, encompassing pro-oxidative proteins and antioxidative proteins. These... (Review)
Review
Ferroptosis is a form of iron-related oxidative cell death governed by an integrated redox system, encompassing pro-oxidative proteins and antioxidative proteins. These proteins undergo precise control through diverse post-translational modifications, including ubiquitination, phosphorylation, acetylation, O-GlcNAcylation, SUMOylation, methylation, N-myristoylation, palmitoylation, and oxidative modification. These modifications play pivotal roles in regulating protein stability, activity, localization, and interactions, ultimately influencing both the buildup of iron and lipid peroxidation. In mammalian cells, regulators of ferroptosis typically undergo degradation via two principal pathways: the ubiquitin-proteasome system, which handles the majority of protein degradation, and autophagy, primarily targeting long-lived or aggregated proteins. This comprehensive review aims to summarize recent advances in the post-translational modification and degradation of proteins linked to ferroptosis. It also discusses strategies for modulating ferroptosis through protein modification and degradation systems, providing new insights into potential therapeutic applications for both cancer and non-neoplastic diseases.
PubMed: 38955112
DOI: 10.1016/j.redox.2024.103259 -
Biomedicine & Pharmacotherapy =... Jul 2024Hepatic cancer is one of the main causes of cancer-related death worldwide. Cancer stem cells (CSCs) are a unique subset of cancer cells that promote tumour growth,...
Ruthenium complex containing 1,3-thiazolidine-2-thione inhibits hepatic cancer stem cells by suppressing Akt/mTOR signalling and leading to apoptotic and autophagic cell death.
Hepatic cancer is one of the main causes of cancer-related death worldwide. Cancer stem cells (CSCs) are a unique subset of cancer cells that promote tumour growth, maintenance, and therapeutic resistance, leading to recurrence. In the present work, the ability of a ruthenium complex containing 1,3-thiazolidine-2-thione (RCT), with the chemical formula [Ru(tzdt)(bipy)(dppb)]PF, to inhibit hepatic CSCs was explored in human hepatocellular carcinoma HepG2 cells. RCT exhibited potent cytotoxicity to solid and haematological cancer cell lines and reduced the clonogenic potential, CD133 and CD44 cell percentages and tumour spheroid growth of HepG2 cells. RCT also inhibited cell motility, as observed in the wound healing assay and transwell cell migration assay. RCT reduced the levels of Akt1, phospho-Akt (Ser473), phospho-Akt (Thr308), phospho-mTOR (Ser2448), and phospho-S6 (Ser235/Ser236) in HepG2 cells, indicating that interfering with Akt/mTOR signalling is a mechanism of action of RCT. The levels of active caspase-3 and cleaved PARP (Asp214) were increased in RCT-treated HepG2 cells, indicating the induction of apoptotic cell death. In addition, RCT modulated the autophagy markers LC3B and p62/SQSTM1 in HepG2 cells and increased mitophagy in a mt-Keima-transfected mouse embryonic fibroblast (MEF) cell model, and RCT-induced cytotoxicity was partially prevented by autophagy inhibitors. Furthermore, mutant Atg5 MEFs and PentaKO HeLa cells (human cervical adenocarcinoma with five autophagy receptor knockouts) were less sensitive to RCT cytotoxicity than their parental cell lines, indicating that RCT induces autophagy-mediated cell death. Taken together, these data indicate that RCT is a novel potential anti-liver cancer drug with a suppressive effect on CSCs.
PubMed: 38955086
DOI: 10.1016/j.biopha.2024.117059 -
Thrombosis Research Jun 2024Fibroblast activation protein-α (FAP), a type-II transmembrane serine protease, is associated with wound healing, cancer-associated fibroblasts, and chronic fibrosing...
BACKGROUND
Fibroblast activation protein-α (FAP), a type-II transmembrane serine protease, is associated with wound healing, cancer-associated fibroblasts, and chronic fibrosing diseases. However, its expression in deep vein thrombosis (DVT) remains unclear. Therefore, this study investigated FAP expression and localization in DVT.
METHODS
We performed pathological analyses of the aspirated thrombi of patients with DVT (n = 14), classifying thrombotic areas in terms of fresh, cellular lysis, and organizing reaction components. The organizing reaction included endothelialization and fibroblastic reaction. We immunohistochemically examined FAP-expressed areas and cells, and finally analyzed FAP expression in cultured dermal fibroblasts.
RESULTS
All the aspirated thrombi showed a heterogeneous mixture of at least two of the three thrombotic areas. Specifically, 83 % of aspirated thrombi showed fresh and organizing reaction components. Immunohistochemical expression of FAP was restricted to the organizing area. Double immunofluorescence staining showed that FAP in the thrombi was mainly expressed in vimentin-positive or α-smooth muscle actin-positive fibroblasts. Some CD163-positive macrophages expressed FAP. FAP mRNA and protein levels were higher in fibroblasts with low-proliferative activity cultured under 0.1 % fetal bovine serum (FBS) than that under 10 % FBS. Fibroblasts cultured in 10 % FBS showed a significant decrease in FAP mRNA levels following supplementation with hemin, but not with thrombin.
CONCLUSIONS
The heterogeneous composition of venous thrombi suggests a multistep thrombus formation process in human DVT. Further, fibroblasts or myofibroblasts may express FAP during the organizing process. FAP expression may be higher in fibroblasts with low proliferative activity.
PubMed: 38955058
DOI: 10.1016/j.thromres.2024.109075 -
Bioorganic Chemistry Jun 2024The c-ros oncogene 1 (ROS1), an oncogenic driver, is known to induce non-small cell lung cancer (NSCLC) when overactivated, particularly through the formation of fusion...
The c-ros oncogene 1 (ROS1), an oncogenic driver, is known to induce non-small cell lung cancer (NSCLC) when overactivated, particularly through the formation of fusion proteins. Traditional targeted therapies focus on inhibiting ROS1 activity with ROS 1 inhibitors to manage cancer progression. However, a new strategy involving the design of protein degraders offers a more potent approach by completely degrading ROS1 fusion oncoproteins, thereby effectively blocking their kinase activity and enhancing anti-tumour potential. Utilizing PROteolysis-TArgeting Chimera (PROTAC) technology and informed by molecular docking and rational design, we report the first ROS1-specific PROTAC, SIAIS039. This degrader effectively targets multiple ROS1 fusion oncoproteins (CD74-ROS1, SDC4-ROS1 and SLC34A2-ROS1) in engineered Ba/F3 cells and HCC78 cells, demonstrating anti-tumour effects against ROS1 fusion-driven cancer cells. It suppresses cell proliferation, induces cell cycle arrest, and apoptosis, and inhibits clonogenicity. The anti-tumour efficacy of SIAIS039 surpasses two approved drugs, crizotinib and entrectinib, and matches that of the top inhibitors, including lorlatinib and taletrectinib. Mechanistic studies confirm that the degradation induced by 039 requires the participation of ROS1 ligands and E3 ubiquitin ligases, and involves the proteasome and ubiquitination. In addition, 039 exhibited excellent oral bioavailability in a mouse xenograft model, highlighting its potential for clinical application. In conclusion, our study presents a promising and novel therapeutic strategy for ROS1 fusion-positive NSCLC by targeting ROS1 fusion oncoproteins for degradation, laying the foundation for the development of further PROTAC and offering hope for patients with ROS1 fusion-positive NSCLC.
PubMed: 38955003
DOI: 10.1016/j.bioorg.2024.107590 -
Gynecologic Oncology Jul 2024Peritoneal carcinomatosis (PC) is common in patients with advanced gynecologic and gastrointestinal cancers. Frequently, patients with PC undergo palliative surgery or...
BACKGROUND
Peritoneal carcinomatosis (PC) is common in patients with advanced gynecologic and gastrointestinal cancers. Frequently, patients with PC undergo palliative surgery or procedures to manage disease-related complications and side effects. However, there are limited data regarding patients' and family caregivers' decision-making processes about these procedures. Thus, we sought to describe the decision-making experiences of patients with PC who elect to pursue palliative surgical procedures and their family caregivers.
METHODS
We conducted a secondary analysis of qualitative data collected during a pilot randomized controlled trial of BOLSTER, a nurse-led telehealth intervention for patients with PC and their caregivers after an acute hospitalization and palliative procedure. Participants in both study arms described their experiences in semi-structured interviews. We re-analyzed coded qualitative data with a focus on understanding decision-making experiences surrounding palliative surgery and procedures using conventional content analysis.
RESULTS
Interviews from 32 participants, 23 patients and 9 caregivers, were analyzed. Participants reported their decision-making was complicated by illness uncertainty and a desire for clear, effective communication with surgical and medical oncology teams. Participants requested more information about the impact of palliative procedures on their daily life. Several also noted that, without improved understanding, a misalignment between patient and family caregiver goals and palliative procedures may inadvertently increase suffering.
CONCLUSION
Discussions related to patients' goals and preferences can improve the quality of treatment decision-making in patients with PC and their caregivers. Future research should test interventions to improve advanced cancer patients' illness understanding and decision-making surrounding palliative surgery and procedures.
PubMed: 38954989
DOI: 10.1016/j.ygyno.2024.06.014 -
International Journal of Surgery Case... Jun 2024Mantle cell lymphoma is a rare type of non-Hodgkin's lymphoma which accounts for 5 % of all cases. Patients present with an advanced form of the disease. We present...
INTRODUCTION AND IMPORTANCE
Mantle cell lymphoma is a rare type of non-Hodgkin's lymphoma which accounts for 5 % of all cases. Patients present with an advanced form of the disease. We present here a case of ileocolic intussusception secondary to mantle cell lymphoma which was revealed by abdominal pain and vomiting that was treated by surgical resection followed by chemotherapy.
CASE PRESENTATION
This report illustrates the case of a 34-year-old male who presented with abdominal pain and vomiting. Imageology demonstrated an ileocolic intussusception which was treated with hemicolectomy followed by chemotherapy. Histopathology confirmed the diagnosis of Mantle cell lymphoma.
CLINICAL DISCUSSION
Mantel cell lymphoma is a rare type of B-cell cancer. Patients are generally diagnosed with an advanced stage of the disease. Ileocolic intussusception is an uncommon presentation. Surgery is the pillar of the treatment. Resection depends on the extent and location of the lesion. Postoperative chemotherapy is crucial and it increases survival rate.
CONCLUSION
Mantle cell lymphoma is a rare subgroup of B-cell lymphomas. Ileocolic intussusception is a complicated form of the disease. Surgery combined with chemotherapy is the mainstay of the treatment. Diagnosis is confirmed by histological analysis of the surgical specimen.
PubMed: 38954973
DOI: 10.1016/j.ijscr.2024.109963 -
European Journal of Cancer (Oxford,... Jun 2024The prognosis of patients with advanced biliary tract cancer (BTC) is still poor, and new strategies improving patients' outcome are needed. In our trial we investigated...
INTRODUCTION
The prognosis of patients with advanced biliary tract cancer (BTC) is still poor, and new strategies improving patients' outcome are needed. In our trial we investigated safety and activity of nab-paclitaxel in combination with gemcitabine and oxaliplatin as first-line systemic treatment for patients with advanced BTC.
METHODS
In this investigator-initiated, multicenter, dose-escalation, single-arm phase I/II trial, patients were accrued into cohorts of 3 patients and dose escalation was performed following the standard 3 + 3 rule. Primary endpoint was the proportion of patients free from progression at 6 months. Secondary endpoints included safety and tolerability of the combination; progression-free survival (PFS); overall survival (OS); objective response rate (ORR); duration of response.
RESULTS
Between July 2017 and December 2020, 67 patients were treated. Among the 10 patients in the phase I, no dose-limiting toxicity was observed, and dose level 2 was defined as recommended phase II dose for the phase II part. At data cutoff, the 6-month PFS rate was 49.1 % (95 % CI 40.8-57.5 %) with 28 patients out of 57 free from progression or death at 6 months. Median PFS was 6.3 months (95 % CI 3.6-10.1) and median OS was 12.4 months (95 % CI 8-23). ORR was 20.89 %. Most common grade 3 and grade 1-2 drug-related adverse events were neutropenia and peripheral neuropathy, respectively.
CONCLUSION
Triple chemotherapy demonstrated a favorable safety profile. However, the study did not meet its primary endpoint. Future studies will clarify the benefit of chemotherapy combinations in different settings. This trial is registered with ClinicalTrials.gov, NCT03943043.
PubMed: 38954899
DOI: 10.1016/j.ejca.2024.114196