Triple-negative breast cancer (TNBC) is known for its more aggressive clinical behavior, poor prognosis, and distinctive patterns of metastasis. Neoadjuvant chemotherapy (NAC) can influence both tumor cells and the tumor microenvironment. Emerging evidence highlights the critical role of actin cytoskeletal dynamics in cancer progression.

Anaplastic lymphoma kinase (ALK) is an established therapeutic target in non-small cell lung cancer (NSCLC), predominantly identified in adenocarcinomas. However, ALK rearrangements also occur in de novo squamous and adenosquamous NSCLCs and their clinicogenomic features remain poorly defined.

To describe the clinical presentation, surgical management, and reconstruction of maxillary odontogenic myxomas through two case reports, and to propose a comprehensive management algorithm to guide diagnosis and treatment decisions.

Pancreatic neuroendocrine neoplasms (PanNENs) represent a rare and heterogeneous group of tumors with diverse biological behaviors and clinical outcomes, posing significant therapeutic challenges. Recent studies have suggested that certain proton pump inhibitors, including Lansoprazole, may possess direct anti-tumor properties beyond their classical role in acid suppression; however, their specific effects and molecular mechanisms in PanNENs remain largely unexplored. This study aims to investigate the anti-proliferative effects and elucidate the underlying molecular mechanisms of Lansoprazole in PanNEN models. Our findings demonstrate that Lansoprazole significantly upregulates the expression of DNA Damage Inducible Transcript 3 (DDIT3), a key stress-induced transcription factor. This upregulation leads to the subsequent inhibition of the oncogenic PI3K/AKT/mTOR signaling pathway, a central driver of cell growth and proliferation, resulting in marked suppression of PanNEN cell proliferation in vitro. Furthermore, we explored combination therapy strategies and found that Lansoprazole synergizes with everolimus, an established mTOR inhibitor used in PanNEN treatment. This combination enhances overall anti-tumor efficacy, suggesting a promising synergistic therapeutic strategy for PanNENs. These results not only reveal a novel, drug-repurposing approach for targeting PanNENs but also provide a mechanistic rationale for combining Lansoprazole with standard targeted therapies to improve patient outcomes.

Lung cancer has high mortality rates among both men and women worldwide. Nevertheless, mortality rates have been reported to decline with the advancement of novel therapeutic agents and the identification of new molecular targets. Schiff bases and triazine compounds have significant biological activity. For this purpose, new Schiff base derivative triazine compounds (TrzSchf 1-3) were synthesized in our study. The activities of the new compounds, characterized by spectroscopic techniques, against A549 lung cancer and MRC5 normal lung cells were identified in a series of studies. It was observed that TrzSchf 1-3 generally showed a growth-inhibitory effect against lung cancer cells (A549) and a non-toxic effect against normal lung cells (MRC5). Notably, TrzSchf 1 and TrzSchf 2, 3 exhibited prominent cytotoxic effects in A549 cells, with IC50 values of 14.24 and > 50 μM, respectively. It was observed that the compound with the most potent cytotoxicity against lung cancer cells was TrzSchf 1 (Selective Index: 3.62). In A549 cells, an increase in MAPK gene expression was observed for all compounds. It was observed that the expression of Caspase-3, CD40, CHK1, P27, P38, and P53 proapoptotic proteins increased by all compounds (TrzSchf 1-3), whereas the expression of antiapoptotic proteins such as BCL-2 and NFκB decreased by these compounds. The compounds are thought to be potential inhibitors of BCL-2 and NFκB, which are associated with cell death. Complementary and guiding in silico studies supported the experimental findings. BCL-2 was determined as the most favorable molecular target based on docking scores, and e-pharmacophore modeling further revealed key interaction features and enabled SAR analysis. The drug-likeness potential of the TrzSchf derivatives was evaluated based on Lipinski's Rule of Five parameters. Overall, both experimental and computational results suggest that TrzSchf 1-3 are promising lead candidates for further investigation in lung cancer therapy.

DHP107 is an oral paclitaxel enabling administration of paclitaxel without Cremophor EL, a vehicle used to improve the solubility of intravenous (IV) paclitaxel. The randomized phase II OPERA study investigated the efficacy and safety of DHP107 versus IV paclitaxel in patients with HER2-negative breast cancer.

In this study, we assess the activation of autophagy and its impact on cytotoxicity following [HuArgI (Co)-PEG5000]-induced arginine deprivation in AML cells. We have previously shown that arginine deprivation is selectively cytotoxic to AML cells and that cell death is caspase independent and non-apoptotic, hence the mechanism of cell death remained elusive. We tested a panel of 7 AML cell lines, and we first demonstrated that the cytotoxicity of [HuArgI (Co)-PEG5000] to AML cells is long-term and sustained despite re-expression of overexpression of ASS1 in all cell lines. We also demonstrated that arginine deprivation leads to a prolonged and extensive activation of autophagy starting at 24 and lasting up to 120 h in all cells. Autophagy was shown to induce cell death since its inhibition using chloroquine (CQ) significantly decreased [HuArgI (Co)-PEG5000]-induced cytotoxicity, indicating autophagic cell death in AML cells following arginine deprivation. Moreover, we showed that arginine deprivation leads to ROS accumulation and that neutralizing ROS using N-acetylcysteine (NAC) does not affect the autophagic response but completely reverses the cytotoxicity of arginine deprivation, demonstrating that death by autophagy is dependent on ROS generation in AML cells.

Glioblastoma (GBM) is the most aggressive primary brain tumor and remains refractory to current therapies due to its pronounced metabolic heterogeneity and mitochondrial adaptability. Ion channels, particularly ATP-sensitive-potassium (KATP) channels, have emerged as critical regulators of cellular energy sensing in cancer. This study evaluated the mitochondrial-targeted agent MitoQ in GBM and explored its potential association with KATP channels. In this study, the cytotoxic potential of MitoQ was systematically evaluated in three genetically distinct GBM cell lines. Cell viability was assessed using concentration-response analyses to identify differential sensitivity. Baseline expression of KATP-channel components (KCNJ11/Kir6.2, ABCC8/SUR1, and CCDC51) was quantified by qRT-PCR and Western blotting. Mechanistic analyses were subsequently performed in the most sensitive cell line and included mitochondrial ROS measurement (MitoSOX), confocal assessment of mitochondrial morphology, Seahorse XF-based bioenergetic profiling, ATP/ADP ratio quantification, analysis of autophagic flux via LC3-II/p62 turnover with bafilomycin-A1, and caspase-3/7-based apoptosis detection. U87 cells exhibited the lowest IC₅₀ for MitoQ and showed significantly higher baseline expression of KATP channel subunits compared to U251 and T98G cells. Acute MitoQ exposure (10 µM, 6 h) in U87 cells induced marked mitochondrial superoxide accumulation, extensive mitochondrial fragmentation, severe suppression of oxidative phosphorylation, and ATP depletion. These effects were associated with selective downregulation of Kir6.2 and the mitochondrial KATP-associated component CCDC51, impaired autophagic flux with p62 accumulation, and robust activation of executioner caspases. In conclusion, MitoQ may induce mitochondrial dysfunction in metabolically primed GBM cells, and cellular sensitivity appears to correlate with a distinct KATP channel expression signature.

Triple-negative breast cancer (TNBC) is an aggressive subtype characterized by early relapse and limited therapeutic options. Carboplatin added to anthracycline/taxane neoadjuvant chemotherapy (NACT) raises pathologic complete response (pCR) rates. The role of adjuvant capecitabine following NACT containing carboplatin remains unclear, particularly in real-world settings.

Bladder cancer (BC), a leading urogenital malignancy with high mortality, lacks effective early biomarkers. Connexin 43 (Cx43), encoded by GJA1, regulates tumor growth via protein interactions and phosphorylation. While dysregulated in BC, Cx43's downstream regulatory pathways remain unclear. Elucidating these mechanisms is crucial for identifying novel biomarkers and therapeutic targets. qRT-PCR measured Cx43 expression in bladder cancer tissues and cells. Kaplan-Meier analysis assessed correlation between Cx43 expression and patient overall survival (OS) and progression-free survival (PFS). Using MTT, colony formation, and Transwell assays, we evaluated how silencing Cx43 affects BC cell proliferation, migration, and invasion in vitro. Protein-protein interaction (PPI) analysis predicted potential Cx43 downstream targets. Co-immunoprecipitation (Co-IP) confirmed specific interaction between Cx43 and c-Src proteins. Western blotting (WB) examined effects of Cx43 knockdown on expression of these predicted downstream targets. Finally, in vivo mouse xenografts validated Cx43's role in BC cell tumorigenesis. Cx43 was upregulated in bladder cancer tissues and its elevated expression correlated with poor patient prognosis. Silencing Cx43 significantly suppressed BC cell proliferation, migration, and invasion. Functional rescue experiments implicated the c-Src/PTEN pathway in mediating the oncogenic effects of Cx43. Mechanistically, Cx43 drives BC progression by facilitating c-Src-mediated suppression of the tumor suppressor PTEN and subsequent activation of FAK signaling. This study unveiled a novel regulatory pathway, Cx43 promotes malignant bladder cancer progression by modulating the c-Src/PTEN/p-FAK axis.

Astrocytes are increasingly recognized as active regulators of glioma progression rather than passive bystanders. In addition to blood-brain barrier support, metabolic homeostasis, and synaptic regulation, astrocytes undergo state transitions in response to tumor-derived cues, immune inflammation, and therapy-induced stress. We synthesize evidence from single-cell and single-nucleus transcriptomics, spatial transcriptomics, proteomics, and multiplex imaging to delineate major tumor-associated astrocyte programs across perivascular, invasive-margin, and hypoxic niches. Mechanistically, we highlight how convergent signaling networks, including interleukin-6 (IL-6) family signal transducer and activator of transcription 3 (STAT3), nuclear factor-kappa B (NF-κB), interferon, and transforming growth factor-beta (TGF-β) pathways, couple to metabolic rewiring and chromatin reinforcement to stabilize pro-tumor phenotypes and define molecular inflection points during disease evolution. We propose a 4D spatiotemporal mapping framework that integrates staged sampling with spatially resolved readouts to reconstruct astrocyte trajectories and predict therapy-induced state shifts. To accelerate translation, we separate tumor-derived analytes from astrocyte-derived response analytes within a glial liquid biopsy concept, emphasizing extracellular vesicles, cell-free nucleic acids, and state-linked protein signatures. Finally, we discuss state-aware interventions, spanning pharmacologic modulation and gene therapy, with an emphasis on implementable RNA therapeutics such as small interfering RNA (siRNA)lipid nanoparticles and central nervous system (CNS)-appropriate delivery routes, to restore protective barrier functions while limiting immune exclusion and invasion. We outline endpoint panels for in vivo validation and patient stratification, and identify priorities for clinical translation, including longitudinal sampling, spatial atlases, and combinations of astrocyte normalization with immunotherapy and radiotherapy.

In colorectal cancer (CRC), diverting ileostomy prevents the occurrence and severity of anastomotic leakage (AL) during surgery. However, an ileostomy cannot prevent reoperation due to severe AL in some cases, and an approach other than ileostomy may be required. This study identified the risk factors of AL and reoperation due to AL in patients with diverting ileostomies.

Squamous intraepithelial lesions are premalignant conditions for anal cancer, the incidence of which is slowly increasing worldwide. These premalignant lesions are commonly found in high-risk individuals such as those who are immunosuppressed, and men who have sex with men. The development of squamous intraepithelial lesions is driven by chronic human papillomavirus infection that induces cellular proliferation and dysplastic modification in mucosal and cutaneous epithelia. Among a wide family of human papillomavirus strains, high-risk genotypes such as human papillomavirus 16 and 18 are responsible for most high-grade precancerous lesions and their subsequent progression to invasive cancer. Historically, premalignant lesions have been described by a variety of different classification systems that has changed as our understanding of their pathophysiology has evolved. Precancerous lesions are currently classified based on the degree of dysplasia in the anal epithelium. Anal intraepithelial neoplasia I or low-grade squamous intraepithelial neoplasia (LSIL) describes a low-grade dysplastic lesion capable of spontaneous regression, while anal intraepithelial neoplasia III or high-grade squamous intraepithelial neoplasia (HSIL) describes those lesions with capacity for infiltration and malignant change. The need for active screening in high-risk groups is now established, as proactive treatment of HSIL significantly reduces the development of anal cancer. High-resolution anoscopy is a diagnostic modality that allows for the identification and treatment of anal dysplasia, halting its progression to squamous cell carcinoma. Using vital dyes and dedicated instruments offering high magnification and resolution, it is possible to visualize and treat very small and/or flat premalignant lesions that would be invisible on standard diagnostic anoscopy. The evolution of artificial intelligence is set to further enhance its diagnostic ability, and shorten the learning curve for its implementation.

Conversion surgery (CS) following induction therapy has emerged as a treatment option for patients with cT4b esophageal cancer previously considered unresectable. Minimally invasive approaches, including thoracoscopic and robot-assisted techniques, are increasingly applied in this setting. However, evidence comparing conversion minimally invasive esophagectomy (C-MIE) with conversion open esophagectomy (C-OE) remains limited. This single-center retrospective study included 66 patients with cT4b esophageal cancer who underwent CS after induction therapy between 2007 and 2023. Patients were classified into C-MIE (n = 41) or C-OE (n = 25) groups. Short-term outcomes, including operative time, blood loss, complications, and hospital stay, as well as long-term outcomes such as recurrence and survival, were compared. Prognostic factors were identified using multivariate Cox analysis. The C-MIE group showed markedly reduced intraoperative blood loss (79 vs. 470 mL, P < 0.001), lower incidence of anastomotic leakage (4.8 vs. 24%, P = 0.04), and shorter intensive care unit stay (3 vs. 4 days, P = 0.03) compared with the C-OE group. Three-year overall survival was higher in the C-MIE group (63.0 vs. 39.6%, P = 0.08), although not statistically significant. Multivariate analysis identified Clavien-Dindo grade ≥ IIIa (HR: 3.73, 95% CI: 1.81-7.67, P < 0.001) and ypStage ≥ III (HR: 3.51, 95% CI: 1.6-8.43, P = 0.001) as independent predictors of poorer survival. C-MIE showed a reduced risk but not significantly (HR: 0.79, 95% CI: 0.37-1.66; P = 0.537). C-MIE was associated with acceptable short-term outcomes and comparable long-term oncologic results to C-OE in patients with cT4b esophageal cancer responding to induction therapy.

Sarcomas account for 1% of adult malignancies, and 80% of them arise from soft tissue. Orbital leiomyosarcoma is an extremely rare tumor with less than 40 cases reported. The most common subsite is the conjunctiva, followed by the eyelid. We present a case of orbital leiomyosarcoma, which presented with progressive prominence of the left globe. The patient was treated with surgery and postoperative radiotherapy. On the last follow-up, the patient is clinically disease-free. A review of the literature on patients with orbital leiomyosarcoma was done, out of which 84% of patients underwent surgery and 42% of patients received radiotherapy. 15% of patients had a childhood history of retinoblastoma (RB). All patients with childhood RB had bilateral disease and a history of childhood radiotherapy for retinoblastoma.

Neuroendocrine carcinomas (NECs) of the urinary bladder are rare, accounting for less than 1% of all bladder malignancies, and are characterized by aggressive behavior and poor prognosis. These tumors can occur as small or large cell subtypes and often mimic high-grade urothelial carcinoma, posing diagnostic challenges. We present five cases of bladder NECs diagnosed at our center, all presenting with hematuria and other lower urinary tract symptoms. Tumor sizes ranged from 4.8 to 7.5 cm, with all demonstrating deep muscle invasion and high proliferative index. Immunohistochemistry confirmed neuroendocrine differentiation. Four patients received platinum-based chemotherapy, and one underwent radical cystectomy. Two patients with advanced-stage disease succumbed early despite therapy. This series highlights the importance of early recognition, accurate histopathological diagnosis, and timely multimodal management. Given their rarity and diagnostic overlap with other high-grade bladder tumors, clinical awareness is crucial.

Sebaceous carcinoma (SC) typically arises in the periocular region but on rare occasions can present within the oral cavity, posing diagnostic and therapeutic challenges. This report describes a 50-year-old male who developed a progressively enlarging ulcero-proliferative lesion in the right buccal mucosa, initially misdiagnosed as squamous cell carcinoma. Histopathological re-evaluation, supported by immunohistochemistry (CK5/6, p63, and epithelial membrane antigen positivity), established the diagnosis of SC, confirming sebaceous differentiation. Despite its atypical location, the tumor behaved aggressively, invading the mandible and necessitating a composite resection and neck dissection, followed by reconstruction with a pectoralis major myocutaneous flap. Postoperative recovery was uneventful, highlighting the efficacy of prompt surgical intervention when diagnosis is accurate. This case underscores the importance of considering SC among differential diagnoses for oral cavity lesions, especially when histological and immunohistochemical findings diverge from common oral malignancies. A collaborative effort among pathologists, radiologists, and surgeons remains critical for early detection, appropriate management, and improved patient outcomes.

Clear cell renal cell carcinoma (ccRCC) with hemangioblastoma-like features is a recently described new entity, with only 4 cases reported in the English literature to date. It is characterized by the presence of a hemangioblastoma-like component which shares the same morphologic and phenotypic features with renal hemangioblastoma associated to an unequivocal ccRCC component. Transition between both components is gradual. The diagnosis is challenging, especially when ccRCC component is scattered, the tumor might be diagnosed as a hemangioblastoma. In fact, distinguishing the latter from ccRCC with hemangioblastoma-like features is essential for providing patients with the best available treatments. In this article, we describe a new case of ccRCC with hemangioblastoma in a 30-year-old woman to raise awareness of this rare entity presenting a challenging diagnosis.

Extramedullary leukaemia, also known as myeloid sarcoma, is a rare manifestation of acute myeloid leukaemia (AML) that typically occurs in conjunction with bone marrow involvement. It is characterized by infiltration of leukemic cells into extramedullary tissues, including the skin, soft tissues, and lymph nodes, where it may present as mass-like or nodular lesions. When associated with high-risk cytogenetic abnormalities, extramedullary disease may exhibit particularly aggressive behaviour and pose substantial diagnostic challenges, especially when it precedes or masks systemic manifestations of AML.

The outcomes of elderly patients with lymphoma are poor. There is scarcity of data on outcomes of chemotherapy-free regimens in patients older than 80 years with a B-cell lymphoma. We report three octogenarians with B-cell NHL and the efficacy and safety of a nonchemotherapy regimen using a lower dose of polatuzumab vedotin and anti-CD20 monoclonal antibody. No infusion-related adverse events were noted. No patient developed neutropenia. Peripheral neuropathy was grade 2 in all cases. Recurrent UTI were a concern in two patients. After a median of 6 cycles (range 1-6) of polatuzumab therapy, all three patients had achieved CR. One patient was lost to follow-up and succumbed to a multidrug-resistant gram-negative UTI. One patient relapsed at 13 months and other is doing well in remission at 15 months.