Search Results (119)

In B-cell chronic lymphocytic leukemia (B-CLL), hypodiploidy is a rare but aggressive subtype of the disease with a very bad prognosis. Hypodiploidy, in contrast to normal B-CLL chromosomal aberrations, is marked by widespread genomic instability, which promotes treatment resistance and quick illness development. Its persistence after treatment implies that chromosomal loss gives cancerous clones a selection edge, which is made worse by telomere malfunction and epigenetic changes. Since thorough genetic profiling has a major impact on patient outcomes, advanced diagnostic methods are crucial for early detection. Treatment approaches must advance beyond accepted practices because of its resistance to traditional medicines. Hematopoietic stem cell transplantation (HSCT) and chimeric antigen receptor (CAR) T-cell therapy are two potential new therapeutic modalities. Relapse and treatment-related morbidity continue to be limiting concerns, despite the noteworthy improvements in outcomes in high-risk CLL patients receiving HSCT. Although more research is required, CAR T-cell treatment is effective in treating recurrent B-ALL and may also be used to treat B-CLL with hypodiploidy. Novel approaches are essential for enhancing patient outcomes and redefining therapeutic success when hypodiploidy challenges established treatment paradigms. Hypodiploidy is an uncommon yet aggressive form of B-CLL that has a very bad prognosis. Hypodiploidy represents significant chromosomal loss and structural imbalance, which contributes to a disordered genomic environment, in contrast to more prevalent cytogenetic changes. This instability promotes resistance to certain new drugs as well as chemoimmunotherapy and speeds up clonal evolution. Its persistence after treatment implies that hypodiploid clones have benefits in survival, which are probably strengthened by chromosomal segregation issues and damaged DNA repair pathways. Malignant progression and treatment failure are further exacerbated by telomere erosion and epigenetic dysregulation. The need for more sensitive molecular diagnostics is highlighted by the fact that standard karyotyping frequently overlooks hypodiploid clones, particularly those concealed by endoreduplication, despite the fact that these complications make early and correct diagnosis crucial. Hypodiploidy requires a move toward individualized treatment because of their link to high-risk genetic traits and resistance to conventional regimens. Although treatments like hematopoietic stem cell transplantation and CAR T-cells show promise, long-term management is still elusive. To improve long-term results and avoid early relapse, addressing this cytogenetic population necessitates combining high-resolution genomic technologies with changing therapy approaches. Full article

Background/Objectives: Extranodal NK-/T-cell lymphoma (ENKTCL) is a rare and highly aggressive lymphoma with a bad prognosis. The aim of our analysis is to evaluate existing research on the potential usefulness of fluorine-18-fluorodeoxyglucose positron emission tomography or positron/computed tomography (2-[18F]FDG PET or PET/CT) in the management of patients with ENKTCL. Methods: A complete search of the literature was conducted across Scopus, PubMed/MEDLINE, and Embase databases, focusing on articles published up to March 2025. Results: A total of 21 studies that investigated the role of 2-[18F]FDG PET or PET/CT in ENKTCL were included in our analysis. The main findings from the literature analysis were (1) 2-[18F]FDG PET/CT seems to be helpful in staging settings, showing a better diagnostic performance than conventional imaging and a positive impact on clinical stage; (2) 2-[18F]FDG PET/CT had excellent negative predictive value for detecting bone marrow involvement, especially in early-stage disease; and (3) qualitative and semiquantitative PET parameters might predict prognosis. Conclusions: Despite several limitations affecting this analysis, especially related to the heterogeneity of the studies included, 2-[18F]FDG PET/CT seems to be a useful tool for the evaluation of ENKTCL. Full article

Triple negative breast cancer (TNBC) is the most aggressive molecular subtype and it lacks targetable receptors. Patients have an increased risk of recurrence and poor prognosis. Little is known concerning the characteristics of disseminated tumor cells (DTCs) and their role in TNBC patients. We analyzed the bone marrow aspirates of 80 patients with primary (n = 67) or recurrent (n = 13) TNBC, using a multi-parameter immunofluorescence staining procedure, including Pan-CK as an epithelial marker, vimentin (vim) as a marker of epithelial–mesenchymal transition, Ki67 for cell proliferation, and HER2 as well as PD-L1 as therapy-related markers. The DTC positive rate was 56% (n= 45) among the cohort. We found 20 different DTC subpopulations. The most frequently detected profile was CK+Vim+Ki67+ (n = 75 cells). The occurrence of CK- DTCs (n = 69) was significantly correlated to PD-L1 (r = −0.305, p < 0.01) and HER2 positivity (r = −0.234, p < 0.001). DTC positive patients that received neoadjuvant chemotherapy (NACT) and did not reach pathologic complete response were more likely to have CK- DTCs. Our data indicate that the occurrence of DTC subpopulations positive for Vim, Ki67, and HER2 appear to be markers for bad prognosis and could be therapeutically relevant. Furthermore, our results raise the question of whether DTCs are dormant in TNBC patients and persistent towards chemotherapy. Full article

Esophageal squamous cell carcinoma (ESCC) is a prevalent malignancy characterized by poor prognosis and a deficiency of effective therapies. Brusatol (Bru), a bioactive component derived from Brucea javanica, exhibits potent anti-tumor activity. However, the pro-apoptotic and anti-metastatic effects of Bru in ESCC remain unclear. ESCC cells were incubated with Bru. The apoptotic status and metastatic capacities of the cells was measured by the Annexin V-FITC/PI, and wound-healing and transwell assays. Potential targets of Bru in ESCC were identified. The mechanisms by which Bru exerts its effects in ESCC cells were explored. Additionally, the typical 4-NQO-induced ESCC mouse model was employed to examine the anti-tumor effect of Bru in vivo. In this study, Bru was found to trigger mitochondria-mediated cell apoptosis (approximately 5.9- and 3.3-fold increases in the level of apoptosis at high concentrations (80 nM) in the KYSE30 and KYSE450 cells) and inhibit metastasis (49% wound closure decreases at high concentrations (80 nM) in both cells, compared to that in the DMSO group) in ESCC cells. In vivo, Bru significantly suppressed ESCC tumorigenesis. Notably, Bru interacts with Akt1, leading to a reduction in the phosphorylation level of Akt1 at Ser473. Consequently, this not only induced dephosphorylation of Bad at the Ser136 residue to promote mitochondrial apoptosis but also inhibited metastasis in ESCC cells. Bru promoted Bad-mediated mitochondrial apoptosis and inhibited the ESCC cell metastasis by targeting Akt1. Our results suggest Bru is a novel Akt1 inhibitor for inhibiting the progression of ESCC. Full article

Globally, lung cancer is the primary cause of deaths associated with cancer; however, current therapies are costly and toxic, highlighting the need for novel treatments. Peiminine (Verticinone), a key bioactive compound derived from Fritillaria ussuriensis Maxim., has demonstrated diverse biological activities. However, the precise pharmacological mechanisms underlying its anti-lung cancer effects remain unclear. The objective of this study was to quantify the content of peiminine in Fritillaria ussuriensis Maxim. from different geographical regions using UHPLC-MS/MS and to elucidate the anti-lung cancer mechanisms of peiminine through network pharmacology, bioinformatics, and in vitro experiments. The content of peiminine in Fritillaria ussuriensis Maxim. from various regions was determined using UHPLC-MS/MS. Potential target genes associated with peiminine and lung cancer were systematically screened from multiple databases. To identify core genes, we set up a PPI (protein–protein interaction) network, followed by in-depth analyses of their corresponding target proteins. Survival analysis, molecular docking, and dynamics simulations were used to explore potential anti-cancer mechanisms. In vitro experiments on human H1299 NSCLC cells assessed peiminine’s anti-tumor activity and measured key gene transcription levels. UHPLC-MS/MS analysis revealed that Fritillaria ussuriensis Maxim. from Mudanjiang (Heilongjiang Province) exhibited the highest peiminine content. Network pharmacological analysis identified PIK3CG, SRC, JAK3, AKT2, and PRKCA as key potential targets of peiminine in lung cancer treatment. Molecular docking results demonstrated strong binding affinities between peiminine and PIK3CG, SRC, and JAK3; these results were further confirmed using molecular dynamics simulations. Survival analysis indicated that a high AKT2 and PRKCA expression correlated with bad prognosis in lung cancer patients. In vitro, peiminine inhibited H1299 cell viability and regulated genes involved in the PI3K–Akt pathway (PI3K, AKT, and PTEN) and apoptosis (Bcl-2, Bax), suggesting that it may induce its effects via PI3K–Akt pathway inhibition. Peiminine from Fritillaria ussuriensis Maxim. exhibits significant anti-lung cancer potential by targeting key genes such as PIK3CG, SRC, and JAK3, as well as by modulating the PI3K-Akt signaling pathway and apoptosis-related genes. These results lay a foundation for further investigations into peiminine as a potentially effective therapeutic option for treating lung cancer. Additionally, the identified targets (PIK3CG, SRC, JAK3, AKT2, and PRKCA) may function as possible biomarkers for predicting lung cancer prognosis and guiding personalized therapy. Full article

Background/Objectives: One of the problematic situations dermatologists face with their patients is communicating dismal diagnoses. Examples are the diagnosis and prognosis of skin cancers like melanoma and Merkel cell carcinoma and the disclosure of the chronic nature of a disease that requires long-term therapies or can lead to scarring or disfiguring conditions. Likewise, receiving a diagnosis of a sexually transmitted infection can be a shocking event that can also put into question the patient’s relationship with his/her partner/partners. Some oncology and internal medicine protocols have been developed to support delivering distressing information. Regrettably, no consensus guidelines exist in dermatology, sexually transmitted infections, or other medical specialties. Methods: The protocols available in the literature to guide the disclosure of a dismal diagnosis have been reviewed in the present work. Results: The different protocols consist of several steps, from 5 to 13, and most of them are summarized by acronyms, such as “SPIKES”, “ABCDE”, and “BREAKS”. The frameworks are listened to and explained in the manuscript. Conclusions: These communication models are suggested to be adapted to dermatology and sexually transmitted infections. Indeed, several studies demonstrated that training in communication skills and techniques to facilitate breaking bad news may improve patient satisfaction and physician comfort. Full article

Background: The diagnosis of colorectal cancer (CRC) at early ages has become a challenging trend for oncology due to high rates of mortality worldwide. The correlation of clinical features with young-age prognosis in CRC remains unclear. Therefore, we aimed to describe the clinicopathological features and their impact on the overall survival of young Mexican adults diagnosed with CRC treated in the National Cancer Institute. Methods: This was a retrospective, observational study. The included patients were treated at the National Cancer Institute between 2004 and 2020. The statistical analyses comprised the X² and t tests, Kaplan–Meier, log rank, and Cox regression. Statistical significances were assessed when p was bilaterally < 0.05. Results: A total of 3652 patients diagnosed with CRC attended the National Cancer Institute. Cases of early onset of CRC increased over the 16 years under study, with significant differences between the median age, from 57 in 2004 to 55 years old in 2020 (F = 5.49; gl: 12 p = 0.019). For this analysis, the population was divided in three groups: young (≤30 years), adults (31–70), and elderly (>70). The young population was mostly composed of men (62%; (n = 63), (p = 0.020), with high rates of metastatic disease (44%) (p = 0.001) and right-side tumors (57%), (p = 0.046), and with 44% with a moderate grade (p = 0.750). According to the overall survival (OS) analysis, the median OS was 29 months for young, versus 170 months for adult and 56 months for elderly patients (p <0.001, HR 1.53, 95% CI 1.11–2.10). A sub-analysis was performed considering only patients with metastatic disease. The median OS was 12 months for young, versus 17 and 9 months for adults and elderly (p = 0.08, HR 1.27, 95% CI 1.02–1.46). Conclusions: CRC diagnosis in the young population is increasing due unhealthy lifestyle habits and lack of screening. This population have clinical features of bad prognosis, such as left side, poor grade differentiation, and metastatic disease, precluding prognosis and OS. Full article

Activating FLT3 mutations plays a crucial role in leukemogenesis, but identifying the optimal candidates for FLT3 inhibitor therapy remains controversial. This study aims to explore the impacts of FLT3 mutations in pediatric acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) and to compare the mutation profiles between the two types to inspire the targeted application of FLT3 inhibitors. We retrospectively analyzed 243 ALL and 62 AML cases, grouping them into FLT3-mutant and wild-type categories, respectively. We then assessed the associations between FLT3 mutations and the clinical manifestations, genetic characteristics, and prognosis in ALL and AML. Additionally, we compared the distinct features of FLT3 mutations between ALL and AML. In ALL patients, those with FLT3 mutations predominantly exhibited hyperdiploidy (48.6% vs. 14.9%, p < 0.001) and higher FLT3 expression (108.02 [85.11, 142.06] FPKM vs. 23.11 [9.16, 59.14] FPKM, p < 0.001), but lower expression of signaling pathway-related genes such as HRAS, PIK3R3, BAD, MAP2K2, MAPK3, and STAT5A compared to FLT3 wild-type patients. There was no significant difference in prognosis between the two groups. In contrast, AML patients with FLT3 mutations were primarily associated with leucocytosis (82.90 [47.05, 189.76] G/L vs. 20.36 [8.90, 55.39] G/L, p = 0.001), NUP98 rearrangements (30% vs. 4.8%, p = 0.018), elevated FLT3 expression (74.77 [54.31, 109.46] FPKM vs. 34.56 [20.98, 48.28] FPKM, p < 0.001), and upregulated signaling pathway genes including PIK3CB, AKT1, MTOR, BRAF, and MAPK1 relative to FLT3 wild-type, correlating with poor prognosis. Notably, internal tandem duplications were the predominant type of FLT3 mutation in AML (66.7%) with higher inserted base counts, whereas they were almost absent in ALL (6.3%, p < 0.001). In summary, our study demonstrated that the forms and impacts of FLT3 mutations in ALL differed significantly from those in AML. The gene expression profiles of FLT3-related pathways may provide a rationale for using FLT3 inhibitors in AML rather than ALL when FLT3 mutations are present. Full article

Gastric cancer (GC) is a major cause of cancer-related mortality worldwide. It is often associated with a bad prognosis because of its asymptomatic phenotype until advanced stages, highlighting the need for its prevention and early detection. GC development is preceded by the emergence of gastric preneoplasia lesions (GPNLs), namely atrophic gastritis (AG), intestinal metaplasia (IM), and dysplasia (DYS). GC is currently diagnosed by endoscopy, which is invasive and costly and has limited effectiveness for the detection of GPNLs. Therefore, the discovery of non-invasive biomarkers in liquid biopsies, such as blood samples, in order to identify the presence of gastric preneoplasia and/or cancer lesions at asymptomatic stages is of paramount interest. This comprehensive review provides an overview of recently identified plasma/serum proteins and their diagnostic performance for the prediction of GPNLs and early cancer lesions. Autoantibodies appear to be promising biomarkers for AG, IM and early gastric cancer detection, along with inflammation and immunity-related proteins and antibodies against H. pylori virulence factors. There is a lack of specific protein biomarkers with which to detect DYS. Despite the need for further investigation and validation, some emerging candidates could pave the way for the development of reliable, non-invasive diagnostic tests for the detection and prevention of GC. Full article

Triple-negative breast cancer (TNBC) represents an aggressive subtype of breast cancer, with a bad prognosis and lack of targeted therapeutic options. Characterized by the absence of estrogen receptors, progesterone receptors, and HER2 expression, TNBC is often associated with a significantly lower survival rate compared to other breast cancer subtypes. Our study aimed to explore the prognostic significance of 83 immune-related genes, by using transcriptomic data from the TCGA database. Our analysis identified the Poliovirus Receptor-Like 3 protein (PVRL3) as a critical negative prognostic marker in TNBC patients. Furthermore, we found that the Enhancer of Zeste Homolog 2 (EZH2), a well-known epigenetic regulator, plays a pivotal role in modulating PVRL3 levels in TNBC cancer cell lines expressing EZH2 along with high levels of PVRL3. The elucidation of the EZH2-PVRL3 regulatory axis provides valuable insights into the molecular mechanisms underlying TNBC aggressiveness and opens up potential pathways for personalized therapeutic intervention. Full article

Sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) is a rare liver vascular condition, potentially life-threatening, with clinical signs of portal hypertension, frequently reported in relation to bone marrow transplantation and possibly in non-transplantation-related chemotherapy. We report the case of a 65-year-old female patient who insidiously developed fatigue, mild tenderness of the right upper abdominal quadrant, hepato-splenomegaly and slight weight gain consecutive to ascites development, as well as persistent elevation of transaminases and mild thrombocytopenia. To note, she had a previous history of colorectal cancer (CRC) with liver metastases and several courses of chemotherapy. Abdominal duplex and elastography measurements made the diagnosis of cirrhosis improbable. A lot of lab work-ups were performed in order to rule out several diseases and conditions. Further, transjugular access was used to perform the measurement of the hepatic venous pressure gradient and liver biopsy that confirmed SOS/VOD. In late 2023, she was diagnosed with endometrial adenocarcinoma, requiring chemotherapy again. At present, the liver condition is stationary, but the prognosis is, however, uncertain. In conclusion, we presented the atypical case of a female patient who developed portal hypertension syndrome associated with the late onset of SOS/VOD, after 5-fluorouracil and oxaliplatin chemotherapy for CRC and liver metastases, subsequently diagnosed with endometrial adenocarcinoma, which posed many diagnostic and therapeutic challenges. Given the potentially bad outcome, an early diagnosis of SOS/VOD in patients receiving drugs of risk is important not only to stratify further risk, but also to initiate an appropriate therapy in order to improve the prognosis. Full article

Background: Homologous recombination deficiency (HRD) has evolved into a major diagnostic marker in high-grade ovarian cancer (HGOC), predicting the response to poly (adenosine diphosphate-ribose) polymerase inhibitors (PARPi) and also platinum-based therapy. In addition to HRD, the type of peritoneal tumor spread influences the treatment response and patient survival; miliary type tumor spread has a poorer predicted outcome than non-miliary type tumor spread. Methods: Known methods for HRD assessment were adapted for our technical requirements and the predictive-value integrated genomic instability score (PIGIS) for HRD assessment evolved as an outcome. PIGIS was validated in HGOC samples from 122 patients. We used PIGIS to analyze whether the type of tumor spread correlated with HRD status and whether this had an impact on survival. Results: We demonstrated that PIGIS can discriminate HRD-positive from HRD-negative samples. Tumors with a miliary tumor spread are HRD-negative and have a very bad prognosis with a progression-free survival (PFS) of 15.6 months and an overall survival (OS) of 3.9 years. However, HRD-negative non-miliary spreading tumors in our cohort had a much better prognosis (PFS 35.4 months, OS 8.9 years); similar to HRD-positive tumors (PFS 34.7 months, OS 8.9 years). Conclusions: Our results indicate that in a predominantly PARPi naïve cohort, the type of tumor spread and concomitant cytoreduction efficiency is a better predictor of survival than HRD and that HRD may be an accidental surrogate marker for tumor spread and concomitant cytoreduction efficiency. It remains to be determined whether this also applies for sensitivity to PARPi. Full article

The syndrome of heart failure (HF) with preserved ejection fraction (HFpEF) makes up about half of the HF population. The HF mechanisms in these patients are varied and not fully understood. In addition, the term “diastolic HF” was switched to HFpEF because of difficulties in measuring the left ventricular (LV) diastolic performance. In the late stages, HFpEF carries a prognosis that is as bad as or worse than that of HFrEF. Hence, it is important to recognize LV diastolic impairment at an earlier stage so that the causal mechanisms, if any, can be treated to retard its progression. Despite the availability of numerous disease-modifying agents for HFrEF, there are hardly any available treatments for HFpEF. With our aging population, there will be an epidemic of HFpEF and hence this entity needs attention and respect. In this paper, we review the fundamental mechanisms of HFpEF, the physiology of LV filling and how LV diastolic function can be comprehensively measured. We also speculate how this may help with the early recognition of diastolic HF and its treatment. Full article

Osteosarcoma is a highly malignant, painful cancer with poor treatment opportunities and a bad prognosis. Transient receptor potential ankyrin 1 (TRPA1) and vanilloid 1 (TRPV1) receptors are non-selective cation channels that have been of great interest in cancer, as their expression is increased in some malignancies. In our study we aim to characterize the expression and functionality of the TRPA1 and TRPV1 channels in human and mouse osteosarcoma tissues and in a mouse cell line. TRPA1/Trpa1 and TRPV1/Trpv1 mRNA expressions were demonstrated by PCR gel electrophoresis and RNAscope in situ hybridization. The function of these channels was confirmed by their radioactive ₄₅Ca²⁺ uptake in response to the TRPA1 agonist, Allyl-isothiocyanate (AITC), and TRPV1 agonist, capsaicin, in K7M2 cells. An ATP-based K2M7 cell viability luminescence assay was used to determine cell viability after AITC or capsaicin treatments. Both TRPA1/Trpa1 and TRPV1/Trpv1 were expressed similarly in human and mouse osteosarcoma tissues, while Trpa1 transcripts were more abundantly present in K7M2 cells. TRPA1 activation with 200 µM AITC induced a significant ₄₅Ca²⁺ influx into K7M2 cells, and the antagonist attenuated this effect. In accordance with the lower Trpv1 expression, capsaicin induced a moderate ₄₅Ca²⁺ uptake, which did not reach the level of statistical significance. Both AITC and capsaicin significantly reduced K7M2 cell viability, demonstrating EC₅₀ values of 22 µM and 74 µM. The viability-decreasing effect of AITC was significantly but only partially antagonized by HC-030031, but the action of capsaicin was not affected by the TRPV1 antagonist capsazepine. We provide here the first data on the functional expression of the TRPA1 and TRPV1 ion channels in osteosarcoma, suggesting novel diagnostic and/or therapeutic perspectives. Full article

Glioblastoma multiforme (GBM) is a malignancy of bad prognosis, and advances in early detection and treatment are needed. GBM is heterogenous, with varieties differing in malignancy within a tumor of a patient and between patients. Means are needed to distinguish these GMB forms, so that specific strategies can be deployed for patient management. We study the participation of the chaperone system (CS) in carcinogenesis. The CS is dynamic, with its members moving around the body in extracellular vesicles (EVs) and interacting with components of other physiological systems in health and disease, including GBM. Here, we describe the finding of high amounts of Hsp70 (HSPA1A) and the calcitonin receptor protein (CTR) in EVs in patients with GBM. We present a standardized protocol for collecting, purifying, and characterizing EVs carrying Hsp70 and CTR in plasma-derived EVs from patients with GBM. EVs from GBM patients were obtained just before tumor ablative surgery (T0) and 7 days afterwards (T1); Hsp70 was highly elevated at T0 and less so at T1, and CTR was greatly increased at T0 and reduced to below normal values at T1. Our results encourage further research to assess Hsp70 and CTR as biomarkers for differentiating tumor forms and to determine their roles in GBM carcinogenesis. Full article