Medical Oncology最新文献

The most prevalent form of primary liver cancer, hepatocellular carcinoma (HCC) poses a significant global health challenge due to its limited therapeutic options. Researchers are currently focused on the complex molecular landscape that governs the initiation and progression of HCC in order to identify new avenues for diagnosis, prognosis, and treatment. In the context of HCC, the Kinesin Superfamily Proteins (KIFs) have become critical regulators of cellular processes, prompting a growing interest in their function among the diverse array of molecular actors implicated in cancer. The KIFs, a family of microtubule-based molecular motors, are renowned for their essential roles in the dynamics of mitotic spindles and intracellular transport. Beyond their well-established functions in normal cellular physiology, emerging evidence indicates that dysregulation of KIFs significantly contributes to the pathogenesis of HCC. Novel therapeutic targets and diagnostic markers are revealed through the unique opportunity to comprehend the complex interplay between KIFs and the molecular events that drive HCC.

Colon adenocarcinoma (COAD) is a prevalent gastrointestinal malignant disease with a high mortality rate, and identification of novel prognostic biomarkers and therapeutic targets is urgently needed. Although NDUFA4L2 has high expressions in various tumors and affects tumor progression, its role in COAD remains unclear. The role of NDUFA4L2 in COAD was analyzed utilizing datasets available from public databases including The Cancer Genome Atlas, The Genotype-Tissue Expression (GTEx), Gene Expression Omnibus, Alabama Cancer Database (UALCAN), and The Human Protein Atlas databases. The prognostic value of NDUFA4L2 was determined using Kaplan-Meier analysis and Cox regression analysis. To investigate the possible mechanism underlying the role of NDUFA4L2 in COAD, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA) were employed. The correlation between NDUFA4L2 expression and immune cell infiltration levels was examined through single-sample gene set enrichment analysis (ssGSEA). The NDUFA4L2 expression levels in COAD patients and cell lines were validated through immunohistochemistry, immunofluorescence, qRT-PCR, and Western blot. Wound healing assay was also performed to evaluate the effect of NDUFA4L2 on COAD metastasis. Furthermore, the NDUFA4L2 mediated competing endogenous RNA (ceRNA) regulatory network was predicted and constructed through a variety of databases. The comprehensive pan-cancer analysis showed that NDUFA4L2 possesses diagnostic and prognostic value in many cancers, especially in COAD. GO-KEGG and GSEA analyses indicated that NDUFA4L2 was associated with multiple biological functions including epithelial-mesenchymal transition and adaptation to hypoxia. The ssGSEA analysis showed that NDUFA4L2 expression was associated with immune infiltration. In vitro experiments confirmed upregulation of NDUFA4L2 in COAD tissues and cell lines, and NDUFA4L2 overexpression significantly promoted migration of COAD cells. In addition, the C9orf139 /miR-194-3p axis was speculated as the possible upstream regulators of NDUFA4L2 in COAD. This study demonstrated that NDUFA4L2 upregulation was correlated with tumor progression, relapsed prognosis and aggressive migration of COAD, suggesting that NDUFA4L2 can act as an effective prognostic biomarker and a promising therapeutic target for COAD treatment.

Non-cancer-related risk factors for secondary lymphedema were defined across four categories: co-morbidity, social determinants of health, behavioral factors, and environmental effectors. Based on rapid reviews of the literature and presentations at the ACS/LANA Lymphedema Summit, this working group categorized these risk factors according to the strength of evidence. Consensus agreement on level of evidence was achieved through one face-to-face working session and three follow-up virtual meetings. Findings elucidate strong evidence for co-morbidities, such as cardio/metabolic and vascular factors contributing to the risk for lymphedema. Evidence is low-to-moderate for social and behavioral factors and is lacking for environmental factors. Panel recommendations suggest a tailored approach to prospective surveillance when monitoring for secondary lymphedema that includes social determinants of health considering the growing awareness and evidence of these factors' influence on cancer and cancer-related morbidity.

Cervical cancer, CC, is one of the malignant cancers in women worldwide. Many studies about the genesis and progression of CC have been done at genomic, transcriptional, translational, and epigenetic levels. However, much less is done at post-translational modification (PTM) level. We first used pan-PTM antibodies to compare the pan PTM levels between clinical normal cervical tissues and CC tissues; we then sent the selected samples for label-free identification of acetylation sites. Next, we employed WT or K119A mutant PARP1-EGFP-STREPII plasmid transfection in Hela cells and examined various indexes including colony formation, wound healing, ROS generation, early apoptosis, and immunofluorescence and quantification of proliferation markers (Ki67, PCNA, and p-P53). Last, we examined the levels of multiple important kinases regulating cervical cancer progression. We found that pan-acetylation was the most downregulated in clinical CC samples, whereas the acetylation of PARP1, Poly(ADP-ribose) polymerase-1, was upregulated at K119. Next, we showed that PARP1-WT overexpression significantly suppressed the proliferation and progression in CC cell line Hela, while K119A overexpression didn't show any impact. Finally, PARP1-WT overexpression significantly decreased p-ERK1/2 while didn't affect the phosphorylation levels of other important kinases such as AKT, MTOR, and RPS6. This study discovered a new type of PTM of PARP1 in CC, and showed that PARP1 acetylation at K119 is essential in regulating the proliferation and progression of CC through ERK1/2. Further studies are required to investigate how PARP1 acetylation impact its function.

Acute lymphoblastic leukemia is a challenging disease to treat, especially in older adults who are most commonly diagnosed and have a high risk of relapse, even with current treatment options. MST-312, targets the RNA component of telomerase, inhibiting its activity and leading to growth arrest and telomere shortening in cancer cells. This study aimed to investigate the effects of MST-312 on apoptosis rates and the expression of telomerase target genes, CCND1, MDM2, MYC, and HSP90AA1, in Jurkat cell line. Jurkat cell line was cultured and treated with various concentrations of MST-312(0 µM, 0.5 µM, 1 µM, 2 µM, and 4 µM). The optimal concentration of MST-312 was determined using MTT assay. Flow cytometry was employed to evaluate the apoptosis induced by MST-312 treatment. The expression levels of the target genes were measured using real-time polymerase chain reaction before and after the treatment with MST-312. P-value < 0.05 was considered statistically significant. The percentages of apoptotic cells after 48 h, as determined by flow cytometry analysis, were 30.32%, 52.35%, 57.60%, and 68.82%, respectively, compared to the control group which was 4.6%. The expression levels of all genes, including CCND1, MDM2, MYC, and HSP90AA1, were decreased compared to the control group. The results showed that MST-312 induced dose- and time-dependent apoptosis and downregulated the expression of CCND1, MDM2, MYC, and HSP90AA1in Jurkat cell line.

Extensive research supports an evidence-base for cancer treatment-related risk factors, including extent of lymph node dissection and use of radiotherapy, as contributing to secondary lymphedema. Additionally, comorbidities, such as higher body mass index, and vascular-related conditions are identified to further augment risk. While social determinants of health (SDOH) and socioeconomic factors are widely regarded as influencing an individual's healthcare outcomes, including cancer risk and survival, these factors have not been explored as risk factors for developing secondary lymphedema. A rapid literature review explored the current evidence for SDOH as risk factors for lymphedema. Studies that were published over the last 10 years and that specifically analyzed social factors as variables associated with lymphedema were included. Studies that only characterized the social determinants of the study population were not included. Forty-nine studies were identified through a rapid literature review, and 13 studies that expressly analyzed social determinants as risk factors for secondary lymphedema were reviewed and extracted. All studies were conducted in patients with breast cancer-related lymphedema. Social risk factors included race, educational level, insurance type, and income level. These are consistent with the socioeconomic inequalities related to cancer survival. SDOH may influence the risk of developing cancer treatment-related health conditions like secondary lymphedema. Research trials studying cancer treatment-related conditions should collect consistent and robust data across social, behavioral, environmental, and economic domains and should analyze these variables to understand their contribution to study endpoints. Risk prediction modeling could be a future pathway to better incorporate social determinants, along with medical and co-morbidity data, to holistically understand lymphedema risk.

Successful personalized oncology today depends on clinicians taking advantage of the extensive, evidence-based information provided by the National Comprehensive Cancer Network (NCCN) Guidelines, which arguably represent the most important advance in cancer care occurring in the last many decades. Personalized oncology also demands that clinicians present guideline information to each patient in a thorough, comprehendible and unbiased manner. Finally, the patient's ability to process that information for shared decision-making about whether an intervention is consistent with their personal preferences, goals and values is perhaps the most important ingredient in truly personalized oncology care. Here, the ethics of sometimes transgressing from the NCCN guidelines with the aim of more personalized care is discussed.

Camptothecin (CPT), an alkaloid isolated from the Camptotheca tree, has demonstrated significant anticancer properties in a range of malignancies. However, its therapeutic efficacy is limited by its hydrophobicity, poor bioavailability, and systemic toxicity. Derivatives, analogues, and nanoformulations of CPT have been synthesized to overcome these limitations. The aim of this review is to comprehensively analyze existing studies to evaluate the therapeutic efficacy, mechanistic aspects, and clinical potential of CPT and its modified forms, including derivatives, analogues, and nanoformulations, in cancer treatment. A comprehensive literature review was performed using PubMed/Medline, Scopus, and Web of Science databases; articles were selected based on specific inclusion criteria, and data were extracted on the pharmacological profile, clinical studies, and therapeutic efficacy of CPT and its different forms. Current evidence suggests that derivatives and analogues of CPT have improved water solubility, bioavailability, and reduced systemic toxicity compared to CPT. Nanoformulations further enhance targeted delivery and reduce off-target effects. Clinical trials indicate promising outcomes with enhanced survival rates and lower side effects. CPT and its modified forms hold significant promise as potent anticancer agents. Ongoing research and clinical trials are essential for establishing their long-term efficacy and safety; the evidence overwhelmingly supports further development and clinical testing of these compounds.