p66Shc is a redox-sensitive and pro-apoptotic adaptor protein that regulates oxidative stress and mitochondrial apoptosis. It is the largest of three isoforms encoded by the proto-oncogene ShcA (Src collagen homologue A). Members of the ShcA family are capable of recruiting various signalling molecules and are involved in several cellular pathways, including proliferation, growth and survival. Increasing evidence highlights the p66Shc role in various tumourigenic processes, such as cell expansion, progression, metastasis and metabolic reprogramming. This review summarises current knowledge on the role of p66Shc in cancer, explains the molecular mechanisms underlying the effects of this protein, and considers therapeutic prospects aimed at targeting it. Emerging therapeutic strategies, including small-molecule inhibitors and gene-editing approaches, are discussed alongside challenges in clinical translation.

Extramedullary haematopoiesis (EMH) refers to blood generation outside of the bone marrow (BM). In Myelofibrosis (MF), a myeloproliferative neoplasm, the disruption of BM microenvironment promotes haematopoietic stem and progenitor cells (HSPCs) mobilisation, resulting in the onset of EMH in the spleen, and then in splenomegaly. Although JAK2 inhibitors have a good efficacy in reducing splenomegaly, the presence of a significant proportion of non-responder patients underlines the need to explore the cellular mechanisms responsible for the EMH onset. In a MF mouse model, Ruxolitinib induces a reduction in spleen volume but does not affect EMH. CD44 inhibition successfully reduces monocyte and HSPC migration in an in vitro extravasation model. Strikingly, MF monocytes are more effective in promoting HSPC migration through the production of hyaluronic acid. Collectively, our results demonstrate that CD44 regulates the migration of monocytes that are crucial for the onset of EMH in MF patients, as they produce CD44 ligands recruiting HSPCs from the BM.

Mucoepidermoid carcinoma (MEC) is the most common malignant neoplasm of salivary gland origin, accounting for approximately 27% of all salivary gland malignancies. While it frequently involves the parotid gland, intraoral cases show a predilection for the palate. Rarely, MEC can arise within the facial skeleton, where it is the most common salivary gland tumor to occur intraosseously. Intraosseous MECs of the jaws are extremely rare and often present diagnostic challenges due to their clinical resemblance to more common jaw lesions. We present a rare case of intraosseous MEC in a 52-year-old male, initially presenting as a recurrent cystic lesion in the maxilla. The case underscores the diagnostic difficulty posed by its unusual histopathological features.

Chemical neurolysis of the brachial plexus and paravertebral space have been sparsely reported. This case involves a patient with refractory pain from stage IV breast cancer, characterized by severe discomfort in the right axilla, shoulder, and pectoral region. A diagnostic block with local anesthetics at T2 and T4 paravertebral spaces and interscalene brachial plexus provided 80% pain relief for 12 hours. Subsequent phenol neurolysis at the same sites achieved 70% sustained pain relief and reduced opioid use for 4 weeks. Chemical neurolysis remains a critical tool in the palliative care arsenal, offering substantial relief in the final stages of life.

Based on our experience, the local anesthetic concentrations used to date in fascial plane blocks may be excessively high. Local anesthetic concentrations previously considered only analgesic (eg, ropivacaine 0.3%) could now be considered anesthetic concentrations with the addition of the right adjuvants and with the correct execution of fascial plane blocks. In this article, we present the case of a frail woman, who underwent awake surgery for unilateral breast cancer, thanks to ultrasound-guided pectoserratus plane block, with ropivacaine 0.3% and the addition of dexamethasone and dexmedetomidine as adjuvants.

DEK::AFF2 fusion-associated carcinomas of the sinonasal tract are exceedingly rare, with fewer than 100 cases reported worldwide, but probably underrecognized. Recently classified by the WHO as a distinct provisional subtype of non-keratinizing squamous cell carcinoma, these tumors pose significant diagnostic and therapeutic challenges. Their histological resemblance to inverted papillomas and their bland histology in most cases often leads to misdiagnosis, while their aggressive behavior underscores the need for a tailored treatment approach.

We report two cases of DEK::AFF2 fusion-associated carcinomas managed at Saarland University Medical Center. The first case involved a 46-year-old woman who initially presented with recurrent sinonasal inverted papilloma, confirmed through multiple surgical interventions over nearly a decade. In 2023, reevaluation and genetic analysis revealed a DEK::AFF2 fusion. The patient demonstrated an exceptional response to three cycles of neoadjuvant gemcitabine and cisplatin, achieving complete remission on MRI restaging. This allowed a shift to definitive chemoradiotherapy, with sustained disease-free status confirmed by a PET-CT three months post-treatment in July 2024. The second case involved a 66-year-old woman presenting with recurrent inverted papilloma affecting the sinonasal and tympanic regions. Despite multiple surgeries, malignant transformation to invasive squamous cell carcinoma occurred, with lymph node metastasis and intracranial spread. A combined otolaryngological and neurosurgical approach was undertaken, but the disease progressed. The patient passed away in January 2020, with postmortem review of the prior histology and genetic analysis confirming DEK::AFF2 fusion carcinoma that showed bland-looking papilloma-like morphology in the initial specimens and later a high-grade cytology indicating biological progression to poorly differentiated carcinoma.

These cases highlight the aggressive nature of DEK::AFF2 fusion-associated carcinomas and the critical role of genetic profiling in diagnosis and management. The exceptional, first ever reported response to neoadjuvant chemotherapy in one case underscores the potential for personalized treatment strategies, warranting further investigation into targeted therapies for this rare malignancy.

ObjectiveCholangiocarcinoma is a lethal malignancy with an increasing incidence and mortality worldwide. Numerous studies have indicated that high-mobility group box 1 is associated with cancer progression. The modulation of subcellular high-mobility group box 1 expression is a major cause of chemotherapeutic drug resistance. This study aimed to demonstrate the role of high-mobility group box 1 in cholangiocarcinoma, including proving the concept of high-mobility group box 1 expression in patients with cholangiocarcinoma, cancer cell growth, migration, invasion, and the modulation of chemotherapeutic drug sensitivity in cholangiocarcinoma cells.MethodsTwenty paraffin-embedded tissue samples were analyzed for high-mobility group box 1 expression using immunohistochemistry. High-mobility group box 1 expression was silenced in KKU-213AL5 cells through siRNA transfection, followed by in vitro assays to assess cell proliferation, migration, invasion, and drug sensitivity. Furthermore, the role of high-mobility group box 1 in regulating growth and metastasis-related signaling pathways was investigated using immunoblotting and protein-protein interaction analysis.ResultsThe results showed that high-mobility group box 1 was highly expressed in cholangiocarcinoma tissues compared to adjacent tissues (p-value < 0.001), as well as the HMGB1 expression analysis from the TCGA database. Silencing high-mobility group box 1 by siRNA transfection resulted in the reduction of cholangiocarcinoma cell growth, migration, and invasion. Interestingly, high-mobility group box 1 silencing enhanced sensitivity to Gemcitabine and Cisplatin by increasing cell cytotoxicity compared to transfection control (p-value = 0.0002 and 0.0258, respectively). We further demonstrated that reduction of high-mobility group box 1 expression attenuates the essential signaling proteins, including Akt, Erk, and cyclin D1, which are crucial in cancer cell growth and metastasis signaling pathways.ConclusionsThis study demonstrates that high-mobility group box 1 plays a critical role in cholangiocarcinoma proliferation, migration and invasion, and may serve as a diagnostic biomarker. Targeting high-mobility group box 1 could enhance therapeutic outcomes, particularly in overcoming drug resistance.

To compile and evaluate characteristics of patients with hypoglossal canal synovial cysts reported in the literature.

Synovial cysts are benign soft-tissue masses that are rarely located in the occipitocervical junction and surrounding anatomical location. They may lead to compression of the hypoglossal nerve. Typically, cysts in this region remain asymptomatic, and biopsies of the hypoglossal canal have high risks, so imaging is a very important diagnostic tool.

A systematic search of PubMed, Medline, Embase, Scopus, and Web of Science was conducted in line with PRISMA guidelines to identify studies on patients with hypoglossal nerve palsy due to synovial cysts. The search strategy followed the authors' predefined PROSPERO protocol. (CRD42024577602) RESULTS: Data were reviewed from 29 patients with hypoglossal nerve palsy due to synovial cysts across 18 studies from 1998 to 2024. There were 12 (41.38%) males and 16 (55.17%) females. The median (range) patient age was 67.0 (51.0-89.0) years. In terms of presenting symptoms, 25 (86.21%) exhibited unilateral tongue atrophy or deviation. Additionally, 9 patients (31.03%) reported swallowing difficulties or dysphagia, and 18 patients (62.07%) experienced slurred speech or dysarthria. In total, 14 (48.27%) patients underwent surgery, while 14 (48.27%) patients received conservative management.

Synovial cysts within the hypoglossal canal are benign lesions that typically appear as T1 hypointense or isointense and T2 hyperintense with peripheral enhancement on magnetic resonance imaging (MRI). Surgical intervention showed very limited improvement in symptoms, particularly when nerve damage was severe and irreversible, while conservative management rarely resulted in cyst regression or symptom relief, and no significant improvement in hypoglossal nerve function.

Curcumin, a bioactive compound derived from Curcuma longa, has gained attention for its potential therapeutic effects in liver cancer. We reviewed current literature to evaluate the efficacy of curcumin in liver cancer models, such as anti-proliferative, pro-apoptotic, anti-inflammatory, or anti-metastatic roles. This systematic review focused on experimental methods, dosages, and underlying mechanisms.

A comprehensive literature search was conducted across PubMed, Web of Science, Embase, and Google Scholar until December 2024. Inclusion criteria were studies using in vivo or in vitro models to assess curcumin's effects on liver cancer, with comparisons to control groups. A total of 26 studies (8 in vivo, 14 in vitro, 4 combined) were included. Data on curcumin administration methods, dosages, and outcomes were extracted. Study quality was assessed using a six-item scale. Descriptive statistics were used for data analysis with SPSS (Version 22.0).

From the initial 1048 studies retrieved, 27 met the inclusion criteria. In vivo studies were conducted on various animals strains (C3H/HeN mice, Wistar rats, B6C3F1 mice, BALB/c nude mice and C57BL/6 mice). Curcumin was administered via oral (8 studies), intraperitoneal (2 studies), intragastric (1 study) and intravenous (1 study) routes, with 8 studies incorporating a dose gradient. The majority of studies used chemically-induced models, including N-diethylnitrosamine (DEN) and nitrosodiethylamine (NDEA) models, as well as subcutaneous injections of liver cancer cell lines (HepG2, Bel7402). The included studies employed various techniques, including Western blotting, RT-PCR, flow cytometry, and migration assays. Curcumin significantly induced apoptosis in liver cancer cells, with 14 studies reporting dose-dependent increases in apoptosis markers such as caspase-3 and Bax expression. Anti-inflammatory effects were evident in 5 studies, with curcumin inhibiting NF-κB activation, a key pathway in liver cancer progression. Additionally, antioxidant and anti-angiogenic properties were observed, as curcumin reduced lipid peroxidation and decreased VEGF expression. Two studies highlighted curcumin's potential in suppressing metastasis, with dose-dependent inhibition of liver cancer cell migration and invasion. The quality of included studies varied, with 21 out of 27 studies employing random allocation and 8 using blinded outcome assessments.

Curcumin demonstrates promising anti-cancer effects, including apoptosis induction, inflammation modulation, and metastasis inhibition. However, variability in study designs and lack of clinical trials necessitate standardized protocols and further clinical investigations to confirm its therapeutic potential in liver cancer treatment.

Our research investigates the role of the YAP1-PPFIBP2 axis in the epithelial-mesenchymal transition (EMT) and its subsequent impact on invasion and migration in head and neck squamous cell carcinoma (HNSCC). Utilizing both in vitro assays and genomic analyses, we demonstrate that YAP1 upregulates EMT by suppressing PPFIBP2/liprin-β2 expression. This regulatory pathway contributes to enhanced invasiveness and correlates with poorer prognostic outcomes in HNSCC. We specifically knocked down YAP1 in SNU1041 and SCC9 cell lines using siRNA, resulting in reduced invasion and migration. These effects were reversed by subsequent administration of siPPFIBP2. In contrast, overexpression of YAP1 in SCC25 cells led to increased EMT marker activity and enhanced invasive behavior, supporting the functional role of this axis. Importantly, pharmacological inhibition of YAP1 using CA3 led to a notable decrease in EMT markers, invasion, and migration, suggesting that blocking the YAP1-PPFIBP2 axis may serve as an effective therapeutic strategy in HNSCC. In conclusion, our study identifies the YAP1-PPFIBP2 interaction as a crucial mediator of tumor aggressiveness in HNSCC, offering new insight into metastatic progression and highlighting a promising target for therapeutic intervention.