This study aimed to explore the clinical benefits of receiving nutritional supplementation (NS) throughout the whole course of chemotherapy. This multicenter prospective cohort study totally included 251 cancer patients requiring nutritional support and scheduled for chemotherapy. Primary outcomes included energy intake (EI), protein intake (PI), body mass index (BMI), NRS 2002 and PG-SGA scores. Short-term efficacy was the secondary outcome. Among the study participants, 168 received NS, whereas 83 opted for dietary advice (DA) alone. In the NS group, EI and PI demonstrated a gradual upward trend across the six cycles of chemotherapy, with no significant changes in the DA group. The BMI remained stable in both groups. The proportion of patients with or at risk of malnutrition showed a declining trend in the NS group but an increasing trend in the DA group. The generalized estimating equation results indicated that NS significantly improved PI (coefficient = 0.19, 95% CI: 0.11 to 0.27, p < 0.001), NRS 2002 (coefficient = -0.13, 95% CI: -0.23 to -0.03, p = 0.005), and PG-SGA (coefficient = -0.18, 95% CI: -0.28 to -0.08, p < 0.001). The improvements in PI, NRS 2002, and PG-SGA scores occurred from cycle 1, cycle 3, and cycle 2, respectively. Multivariate logistic analysis confirmed NS as a favorable factor associated with higher disease control rate (OR = 4.65, 95% CI: [1.88, 12.01], p = 0.001). The incorporation of NS yielded several clinical benefits beyond adequate EI and stable weight. It contributes to higher protein intake and good nutritional status in patients with cancer throughout the whole course of chemotherapy, ultimately improving treatment efficacy. Patient-Reported Outcome Management Including Surveillance and Intervention in Nutritional Group (PROMISING) Study (registration number: ChiCTR2100047535).
Central nervous system (CNS) metastases from Wilms tumor (WT) are exceedingly rare. Intracerebral hemorrhage secondary to metastatic WT is even less common, and the management of such cases is further complicated when patients are receiving a direct oral anticoagulant (DOAC) like Rivaroxaban, for which pediatric reversal guidelines are lacking. We report on the case of a 5-year-old boy with relapsed stage IV Wilms tumor who presented with rapidly progressive neurological deterioration caused by brain metastases with extensive intraparenchymal and intraventricular hemorrhage while receiving Rivaroxaban due to prior thrombosis. An emergent craniotomy and tumor resection was safely performed after emergent reversal of anticoagulation with Rivaroxaban using Andexanet alfa, administered in this pediatric patient with off-label consent in the setting of a life-threatening intracranial hemorrhage requiring emergent neurosurgical intervention. No excessive intraoperative bleeding was noted. Treatment for relapsed WT according to the SIOP-UMBRELLA-Protocol was initiated. Three weeks after Andexanet alfa treatment, a thrombotic event in the left iliac veins occurred, requiring anticoagulation with unfractionated heparin. This case highlights the therapeutic challenges of managing intracranial hemorrhage in a pediatric patient requiring emergent neurosurgical debulking in the setting of Rivaroxaban anticoagulation. To our knowledge, this is the second case reporting on Rivaroxaban reversal through Andexanet alfa in children. Early multidisciplinary intervention, meticulous neurosurgical management and continuation of oncologic therapy can lead to favorable outcomes even in such complex presentations.
Transthoracic CT-guided biopsy performed with the coaxial technique is a minimally invasive procedure that facilitates the diagnosis of lung lesions (nodules or masses) and/or mediastinopulmonary lesions suspected of malignancy. This procedure is the source of several complications, the most frequent of which is pneumothorax. To describe the epidemiological, diagnostic, and therapeutic aspects of iatrogenic pneumothorax after CT-guided biopsy performed using the coaxial technique. Prospective longitudinal study, conducted over a period of 2 years and 10 months, from April 1, 2023, to February 1, 2026, at the Mohammed V Military Teaching Hospital in Rabat, including all patients who presented with a pneumothorax following a transthoracic CT-guided biopsy, according to the coaxial technique, confirmed clinically and/or radiologically. The study included 30 cases of pneumothorax following CT-guided biopsy according to the coaxial technique. Biopsies were performed in 217 patients, and the incidence of pneumothorax was 13.8%. The median age was 68 years [58.8-71.5], with a predominance of males (90%). The most frequent characteristics observed among patients with pneumothorax were pulmonary emphysema (73.3%), lower-lobe lesions (33.3%), and central lesions with a median depth of 3.6 cm [2.9-4.2]. Procedure-related characteristics included practitioner status and biopsy needle diameter (18-gauge). Most patients were asymptomatic (60%). Diagnosis was established by chest CT during the procedure in 26.7% of cases and by chest X-ray after the procedure in 73.3% of cases. Small pneumothorax was the most common presentation (40%). Treatment was conservative in 53.3% of cases, and intervention was required in 46.7% (7 cases drained and 7 cases exsufflated). A complication was observed in 5 cases, after initial treatment. Only one patient underwent thoracoscopic pleurodesis after 14 days of chest drainage. The median length of hospital stay was 4 days [2-5.75]. Pneumothorax is a major complication of CT-guided transthoracic biopsy, whether performed coaxially or non-coaxially. In our descriptive series, pulmonary emphysema, lower-lobe location, and lesion depth were frequent characteristics among patients who developed pneumothorax. We believe that the radiologist's experience is a determining factor in preventing a very high incidence of pneumothorax cases.
Second generation tyrosine kinase inhibitors (TKIs) have improved response rates in patients with chronic phase chronic myeloid leukaemia (CP-CML). Phase 2 trials demonstrated increased deep molecular response rates when combining second generation TKIs with pegylated interferon alfa (Peg-IFN). This trial aimed to evaluate the efficacy and the safety of combining nilotinib with Peg-IFN alfa-2a in patients with newly diagnosed CP-CML. In PETALs, this open-label, randomised, multicentre phase 3 trial, we enrolled patients with newly diagnosed CP-CML from 27 French academic institutions via a centrally-generated electronic system in a 1:1 ratio to two groups: 300 mg oral nilotinib alone twice a day (the nilotinib only group) or 300 mg nilotinib twice a day combined with subcutaneous Peg-IFN (30 μg per week for the first month of treatment and 45 μg per week thereafter) for a maximum of 2 years. The randomly allocated patients were stratified by their Sokal index and European Treatment and Outcome Study long-term survival index. Eligible patients had major BCR::ABL1 transcripts, an Eastern Cooperative Oncology Group performance score of two or lower, who had never received TKIs, and were aged between 18 and 65 years. The primary endpoint was the cumulative rate of molecular response 4·5 (MR4·5; defined as BCR::ABL1 international scale [IS] of 0·0032% and lower), analysed in the intention-to-treat population (n=200). This trial is registered at ClinicalTrials.gov, NCT02201459, and is completed. 205 patients were enrolled between Aug 6, 2014, and Sept 29, 2016, after which five patients were declared ineligible and excluded, resulting in 200 patients being randomly allocated (99 to the nilotinib group and 101 to the combination group). The median age at diagnosis was 45 years (IQR 36-55); 130 patients (65%) were male and 70 (35%) were female. Median follow-up in this cohort was 67 months (IQR 32·6-70·6). The primary objective was met, with higher rates of MR4·5 in the combination group (24% [95% CI 16·0-34·1] vs 15% [8·6-24·2], p=0·048) at month 12. There were equivalent grade 3-4 haematological side effects in the both groups (14 vs 14) with a predominance for grade 3-4 thrombocytopenia without haemorrhages (six in the combination group vs five in the nilotinib group). Psychiatric grade 3-4 events occurred in six (6%) patients in the combination group (including three unsuccessful suicide attempts) compared with five (5%) in the nilotinib group (including one unsuccessful suicide attempt). Six vascular events also occurred in six patients in the combination group and seven vascular events in five patients in the nilotinib group (all grades 3-4). In this setting, Peg-IFN combined with nilotinib induced higher initial rates of MR4·5 compared to TKI monotherapy, despite additional side effects. The onset of psychiatric events might promote immediate cease of Peg-IFN and psychiatrist advice Whether this early molecular response translates into sustained treatment-free survival should be studied in a randomised trial sufficiently powered for this outcome. Novartis Pharma.
Lung cancer is one of the most common malignancies and the leading cause of cancer-related mortality worldwide, posing a major public health challenge. Flavonoids, a large and diverse group of plant metabolites, exhibit various anticancer properties, making them promising candidates for therapeutic applications. This study evaluated the anticancer efficacy of methoxy flavonoids and elucidated their underlying mechanisms of action in A549 lung cancer cells. A549 cells were treated with various flavonoids (AKC1-AKC5), and their effects were analyzed using an MTT assay, DAPI staining, mitochondrial membrane potential (MMP), reactive oxygen species (ROS) production, colony formation, and wound scratch tests. Molecular docking was also performed to confirm the binding of AKC1 and AKC3 to EGFR, BCL-2, and CDK-2 proteins. AKC1 and AKC3 prevented the growth of A549 lung cancer cells with IC50 of 64.57 and 19.80 μM among 5 methoxy flavonoids. AKC1 and AKC3 triggered notable alterations in the shape and reduced the colony-forming potential of A549 cells. The DAPI staining experiment demonstrated that AKC1 and AKC3 impede the growth of cancer cells through activation of apoptotic cell death. Moreover, the anticancer properties of AKC1 and AKC3 were attributed to significant inhibition of MMP and a notable ROS enhancement in a dose-related pattern. The wound scratch assay demonstrated that AKC1 and AKC3 suppressed A549 lung cancer cell migration, suggesting their anti-metastatic properties. Molecular docking studies confirmed that AKC-1 and AKC-3 bind strongly to EGFR, BCL-2, and CDK2, suggesting a multi-target mechanism that underlies their anti-proliferative and pro-apoptotic effects in A549 cells. AKC1 and AKC3 exhibited significant anticancer activity against A549 cells and may serve as promising therapeutic drugs for lung cancer treatment.
Breast cancer is a common malignant tumor with limited treatment options and poor prognosis. SNRPB2, a core spliceosomal component involved in pre-mRNA splicing, is dysregulated in multiple cancers, but its role in breast cancer remains incompletely understood. We analyzed SNRPB2 expression in breast cancer using TCGA, CPTAC, and HPA databases, and assessed its prognostic value via Kaplan-Meier plotter. The biological function of SNRPB2 was evaluated through in vitro cell line assay, and the underlying molecular mechanisms were determined via RNA-seq, RT-qPCR, and additional GEO datasets. Our findings demonstrated that SNRPB2 was significantly overexpressed in breast cancer tissues and correlated with malignant progression and poor prognosis. Knockdown of SNRPB2 induced G2/M cell cycle arrest in cancer cells, decreased expression of numerous genes related to cell cycle and immune modulation, and triggered alterations in multiple alternative splicing events. Mechanistically, SNRPB2 knockdown might promote cancer cell cycle arrest by regulating HMGA2 splicing and expression, while simultaneously suppressing the expression of immune-related genes such as CSF1, CSF1R, IL6, and CX3CL1. Immune infiltration analysis revealed that SNRPB2 expression correlated with increased infiltration of activated inflammatory cells and myeloid-derived suppressor cells. SNRPB2 potentially plays a dual role in promoting breast cancer progression and shaping the immunosuppressive microenvironment, partly through HMGA2 splicing modulation and immune-regulatory gene suppression. These findings suggest that SNRPB2 may represent a promising therapeutic target for breast cancer.
Phakomatoses, also known as neurocutaneous syndromes are rare disorders characterized by multisystem involvement with variable neurological manifestations in children, including intracranial vascular malformations. Cavernous malformations may present with acute haemorrhage and stroke-like symptoms. Diagnostic difficulty arises when radiologic findings suggest a benign lesion, yet histopathology reveals discordant malignant pathology. An 8-year-old female presented with sudden-onset left hemiparesis and recurrent seizures. Physical examination revealed multiple cutaneous naevi, raising suspicion of a syndromic association. Brain magnetic resonance imaging demonstrated a well-circumscribed right parietal intra-axial lesion with a "popcorn" appearance and hypointense susceptibility blooming, highly suggestive of a cavernous malformation. Cranial computed tomography scan subsequently showed an associated large intracerebral haematoma. The patient underwent right parietal craniotomy with haematoma evacuation and excision of the lesion. The immediate postoperative course was initially satisfactory with neurological improvement. Histopathological examination of the excised specimen, however, revealed a malignant neoplasm, establishing a significant radiologic-histologic discordance which fundamentally altered the diagnostic interpretation. The patient had a relapse of symptoms two months after surgery, with repeat neuroimaging showing multicentric tumour recurrence, necessitating referral for adjuvant neuro-oncologic management. This case illustrates a rare diagnostic pitfall and challenge in paediatric neurosurgery, where a malignant intracranial tumour mimicked a cavernous malformation in the context of cutaneous stigmata. The report emphasizes the limitations of neuroimaging alone and underscores the importance of careful clinicoradiologic correlation, histopathological confirmation, and multidisciplinary evaluation when managing presumed vascular lesions in children, particularly in resource-limited settings.
Ropeginterferon alfa-2b is an interferon used in the treatment of myeloproliferative neoplasms, particularly polycythemia vera. Its efficacy in achieving hematologic and molecular responses has been demonstrated in clinical trials, but pooled data on long-term outcomes and sustained response remain limited. This systematic review and meta-analysis aimed to evaluate the hematologic and molecular response over 36 months. PubMed, Scopus, Science Direct, and Google Scholar databases were searched to identify studies reporting hematologic and molecular responses to ropeginterferon alfa-2b. Studies were included if they provided data on complete hematologic response (CHR) and JAK2V617F variant allele frequency (VAF) reduction. Pooled proportions and mean reductions were calculated using random-effects models. The pooled proportion of CHR increased progressively from 0.19 (95% CI: 0.04-0.57) at 3 months to 0.73 (95% CI: 0.17-0.97) at 36 months. Molecular response, measured by VAF reduction, deepened over time from - 7.33 (95% CI: -9.85 to -4.81) at 3 months to -54.90 (95% CI: -65.61 to -43.99) at 36 months. Subgroup analyses revealed significant variability in response rates, particularly in early follow-up periods. Ropeginterferon alfa-2b achieves significant and sustained hematologic and molecular responses over 36 months. This makes it a promising treatment for polycythemia vera. While variability in early responses needs further investigation, the sustained long-term efficacy compared to hydroxyurea supports its use in clinical practice. Future studies should focus on identifying predictors of response and optimizing treatment protocols to maximize patient outcomes.
Breast cancer patients often experience significant psychological distress. This study examined distress trajectories from diagnosis to 6 months post-treatment and explored differences across demographic, medical, and psychosocial subgroups. In this prospective cohort study, 528 patients with breast cancer were recruited between 1 December 2023 and 31 December 2024. Assessments were conducted at baseline (at diagnosis, T0), after the first treatment (T1), mid-treatment (T2), at treatment completion (T3), and at three (T4) and six months (T5) post-treatment. Growth mixture modeling (GMM) was used to identify distinct trajectories of psychological distress. Multinomial logistic regression analysis was performed to examine associations between patient-related factors and trajectory membership. Three psychological distress trajectories were identified: a high-distress remission group (17.05%), a moderate-stable distress group (11.93%), and a low-fluctuating distress group (71.02%). Multivariable analyses showed that higher educational attainment, breast-conserving surgery, early disease stage, partial self-management ability, and strong social support were associated with membership in the moderate-stable or low-fluctuating groups (p < 0.05). Employment, health insurance coverage, avoidant medical coping style, and higher baseline anxiety and depression scores were concurrently associated with membership in the high-distress remission group (p < 0.05). Although psychological distress generally decreased over time, 71.02% of patients followed a low-fluctuating trajectory, 11.93% maintained moderate distress with potential risk of persistence, and 17.05% showed high initial distress that remitted substantially within 6 months. Continuous monitoring and early psychosocial support are recommended, particularly for patients with moderate- or high-risk trajectories.
Head and neck squamous cell carcinoma (HNSCC) is a highly heterogeneous malignancy with poor prognosis and limited predictive biomarkers for therapy response. Characterizing malignant cell heterogeneity may improve prognostic and therapeutic stratification. We integrated single-cell RNA sequencing (scRNA-seq) data from 58 HNSCC patients (181,003 cells) to define malignant cell subpopulations, their differentiation states, developmental trajectories, cell-cell interactions, and spatial localization. Coexpression gene modules and meta-programs were identified using hdWGCNA and NMF. These programs were projected onto bulk RNA-seq datasets to classify HNSCC subtypes and examine associations with clinical outcomes, tumor microenvironment (TME), genomic instability, and predicted response to immune checkpoint inhibitors (ICIs). Twelve malignant clusters were identified with distinct clinical and molecular features. MC-5 exhibited a stem-like phenotype associated with poor prognosis, while MC-7 and MC-11 showed high TME communication and immune engagement. Coexpression analysis revealed 16 modules and eight meta-programs encompassing proliferation, differentiation, stress response, and immune activity. Translation to bulk RNA-seq defined three HNSCC subtypes (MS-1, MS-2, MS-3) with divergent survival, immune infiltration, stromal composition, and genomic features. MS-2, an immune-enriched subtype, demonstrated superior survival, high HPV positivity, and predicted ICI responsiveness. A 25-gene malignant cell score (MCScore) robustly predicted both prognosis and immunotherapy response. This study provides a comprehensive map of malignant cell heterogeneity in HNSCC, identifies key functional expression programs, and defines molecular subtypes with clinical and therapeutic relevance. Malignant cell-specific signatures, such as MCScore, offer promising tools for patient stratification and precision immunotherapy.
Ferroptosis can be inhibited by insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) in cancers. ETS variant transcription factor 4 (ETV4) is aberrantly expressed in various cancers. Elevated transcription of guanosine triphosphate cyclohydrolase 1 (GCH1) contributes to tumor malignancy. This study investigated the involvement of IGF2BP3, ETV4, and GCH1 in ferroptosis in gastric cancer (GC). GC cells and tissue samples were used to detect IGF2BP3, ETV4, and GCH1 expression. The relationships between IGF2BP3, ETV4, and GCH1 were assessed using RNA immunoprecipitation assay, chromatin immunoprecipitation assay, and dual-luciferase reporter assay. BALB/c nude mice were utilized to establish GC tumor xenografts. Cell cloning and Transwell were used to detect the proliferation, migration, and invasion of cells. IGF2BP3 and ETV4 were upregulated in GC. IGF2BP3 regulated ETV4 protein level by mediating its mRNA stability. Knockdown of ETV4 inhibited GC cell proliferation, migration, and invasion, and promoted their ferroptosis. ETV4 also promoted the transcription of GCH1 by directly binding to its promoter region. GCH1 overexpression diminished the facilitating effect of ETV4 knockdown on ferroptosis in GC. Overexpression of GCH1 also eliminated the promoting impact of IGF2BP3 knockdown on GC cell proliferation, migration, and invasion. Lastly, inhibition of GCH1 reversed the promoting effect of IGF2BP3 overexpression on GC tumor growth in vivo. IGF2BP3 promotes tumor growth and inhibits ferroptosis in GC by regulating ETV4, while ETV4 promotes GCH1 expression by direct interaction with its promoter. GCH1 overexpression counteracts the effects of ETV4 and IGF2BP3 on GC. IGF2BP3 and ETV4 are upregulated in GC, and IGF2BP3 regulates ETV4 mRNA stability.Knockdown of ETV4 inhibits GC cell proliferation, migration, and invasion, and promotes their ferroptosis.ETV4 promotes the transcription of GCH1.GCH1 overexpression in GC cells diminishes the impact of ETV4 knockdown.GCH1 inhibition in vivo reverses the facilitating role of IGF2BP3 on GC tumor growth.
The purpose of this study was to examine whether Ki67-scores have a predictive significance for pathological complete response (pCR) and invasive disease-free survival (IDFS) in HER2-positive breast cancer. This retrospective, bi-centric cohort study focused on HER2-positive early breast cancer patients undergoing neoadjuvant chemotherapy from 2015 to 2023. Multivariable logistic regression was used to find independent association between various clinical parameters, including Ki67, and pCR. Ki67-values were categorized into three groups (low ≤ 15%, intermediate 15-35%, high > 35%). Kaplan-Meier estimator calculated differences in IDFS. The study included 244 patients with known Ki67-expression. 147 patients (60.3%) achieved pCR. When categorized, 18 (7.4%) were Ki67 low, 114 (46.7%) Ki67 intermediate and 112 (45.9%) Ki67 high. No correlation between Ki67-score as continuous variable and pCR was observed (p = 0.25). HER2 immunohistochemistry (IHC) score 3 + significantly increased pCR compared to IHC score 2 + (63.2% vs. 45%, p = 0.031). Hormone receptor (HR)-positive tumors had a lower pCR rate (53.1% vs. 74.4%, p = 0.001) compared to HR-negative tumors. 5-year IDFS showed no difference between low Ki67 (88.9%; 95% CI 75.5-100%), intermediate Ki67 (82.0%; 95% CI 72.6-92.7%), and high Ki67 (80.9%, 95% CI 70.1-92.3%) subgroups (p = 0.7). In HER2-positive breast cancer, the Ki67-score showed no association with either pCR or IDFS, thereby questioning its clinical utility. Conversely the HER2 IHC-score and HR-status were predictive indicators for achieving pCR. Clinical decisions in patients with early HER2-positive breast cancer should not be influenced by Ki67-scores, especially not by using cut-offs.
Human papillomavirus (HPV) is a well-established oncogenic virus implicated in the development of several epithelial cancers, most notably cervical, anogenital, and oropharyngeal carcinomas. In contrast, neuroendocrine neoplasms (NENs)-a heterogeneous group of malignancies arising from neuroendocrine cells across various organ systems-have not traditionally been linked to HPV infection. In this study, we performed extensive genomic and transcriptomic profiling to compare HPV-positive NENs to HPV-positive non-NENs across anatomical sites, aiming to uncover biologically and clinically actionable differences. HPV16- and HPV18-positive tumors were identified from 101,343 solid tumors profiled at Caris Life Sciences (Phoenix, AZ) with DNA and RNA sequencing. Prevalence of pathogenic mutations and copy number amplifications were calculated. Fisher's exact/χ2 tests were applied appropriately with p-values adjusted for multiple comparisons (p < 0.05). HPV positivity was most frequent in cervical carcinomas (70%, 1200/1716). Importantly, 6% (96/1620) of NENs from all tissues were positive for HPV16 or HPV18. Among HPV-positive NENs, 93% were high-grade compared to 54% observed in HPV-negative NENs (p < 0.001), highlighting a strong association between HPV and tumor aggressiveness in this subset. Analysis of HPV-associated sites (cervix, anorectal region, and head and neck) revealed that HPV-positive NENs possess distinct genomic and transcriptomic landscapes compared to HPV-positive non-NENs. Notably, interferon signaling was significantly suppressed in HPV-positive NENs, suggesting a unique tumor-immune microenvironment. Our findings indicate that HPV-positive NENs form a distinct subset with unique genomic features, including reduced interferon signaling, compared to HPV-positive non-NENs. Thus, future studies focused on evaluating HPV status, along with genomic and transcriptomic characteristics, may uncover biologically and clinically actionable distinctions for this rare yet clinically significant tumor subgroup. Not applicable.
This study investigates how Chinese breast cancer survivors reconstruct damaged identities and negotiate cultural norms to build resilience within a specific socio-cultural context. Using narrative inquiry and a life-course perspective, in-depth interviews were conducted with 15 female breast cancer survivors in Beijing. The study employed thematic narrative analysis to identify cross-cutting patterns while preserving individual story integrity. Rigor was ensured through data saturation and member checking. Resilience is manifested as a transformative narrative practice across three dimensions: (1) body narrative, survivors transition from chaos narratives to quest narratives, reclaiming identities by ascribing meaning to physical scars; (2) relational narrative, survivors negotiate the tension between Confucian gender expectations and self-care, shifting from stoic endurance to accepting vulnerability; and (3) social narrative, survivors bridge the gap between "silent island" of isolation and collective empowerment by establishing narrative communities that challenge social stigma. These findings reveal a duality of resilience-constrained by cultural structures yet empowered with agency. This study proposes a tripartite social work interventions framework, recommending that social workers act as narrative witnesses, cultural mediators, and community architects. By integrating local cultural wisdom with narrative techniques, social workers can effectively facilitate identity reconstruction and the social integration of breast cancer survivors.
Urological cancers exhibit significant sex differences in incidence, treatment response, and prognosis, with males generally showing higher morbidity and mortality. This review systematically summarizes the underlying molecular and clinical mechanisms of these disparities, focusing on sex hormones, chromosome biology, tumor immune microenvironment, and microbiota. Sex hormones modulate key tumor processes including proliferation, apoptosis, non-apoptotic cell death, and DNA repair. Genetic factors such as X chromosome inactivation escape genes and Y chromosome loss also contribute to sex-biased cancer susceptibility. Furthermore, sex-specific differences in the urinary system and gut microbiota influence local immunity and inflammation, thereby affecting tumor progression and therapeutic response. Lifestyle and environmental factors, including smoking, alcohol consumption, and occupational exposures, further exacerbate these disparities. Clinically, sex differences impact the efficacy of immunotherapy and targeted therapies, underscoring the need for sex-informed treatment strategies. Integrating sex as a biological variable in research, clinical practice, and public health policies is essential for advancing precision oncology in urologic cancers.
Peripheral T-cell lymphoma (PTCL) remains a formidable challenge in clinical management. Histone deacetylase inhibitor chidamide has demonstrated its anti-tumor effects in real-world studies in relapsed or refractory PTCL. To evaluate the efficacy of real-world utilization of chidamide combined with chemotherapy for untreated PTCL and explore relative prognostic factors, a cohort of 151 PTCL patients treated with chidamide combined with chemotherapy as front-line treatment in our center were enrolled. The overall response rate (ORR) and complete remission rate (CRR) at the end of treatment were 81.5% and 67.5%. The 7-year overall survival (OS) rate and progression-free survival (PFS) rate were 67.6% and 49.7%, with a median follow-up period of 21 months, showing its satisfactory efficacy and survival advantage. Most of adverse events were transient and reversible. Furthermore, several baseline characteristics of patients were relevant to prognosis. The study identified gene mutations in TET2 (30.9%), STAT (22.7%), RHOA (17.5%), TP53 (14.4%), DNMT3A (12.4%), with TP53 and DNMT3A mutations correlating with worse clinical outcomes. The identification of gene mutations contributed to personalizing treatment strategies and predicting patient outcomes. This study raised the preliminary hypothesis that chidamide-containing front-line therapy might be promising for PTCL patients, which warranted further investigation.
Ovarian Cancer (OC), the deadliest gynecological malignancy, poses a major therapeutic challenge in advanced stages owing to its high recurrence rate and metastatic potential. In this regard, it is noteworthy that immunotherapy has recently gained significant attention in OC treatment, a phenomenon attributable to notable advances in over-the-counter Chimeric Antigen Receptor (CAR)-based cell therapy. At the heart of CAR-T Cell (CAR-T) immunotherapy is genetically modified CAR molecules that enable immune cells to target and recognize tumor antigens. Based on such strategies, CAR-T therapies have developed rapidly in hematological oncology and are gradually being extended to solid tumors. Despite their potential in OC treatment, several factors, including off-target effects attributable to the lack of Tumor-Specific Antigens (TSAs), as well as severe side effects such as tumor immune barriers, Cytokine Release Syndrome (CRS), and neurotoxicity, have been established to limit the clinical use of CAR-T therapies. Moreover, compared to CAR-T, CAR-Natural Killer (NK) and CAR-Macrophage (M) therapies have distinct advantages. The killing mechanism of NK cells integrates both CAR-dependent and non-dependent pathways, avoiding severe CRS and neurotoxicity. Furthermore, besides directly phagocytosing tumors due to its strong ability to infiltrate tumors, CAR-M therapy could also effectively improve the Immunosuppressive Microenvironment (IME) via immunomodulatory factor secretion to remodel M2-type Tumor-Associated Macrophages (TAMs) into the M1 phenotype with anti-tumor function. In this review, we systematically describe the research progress in CAR-T therapy for OC and compare the similarities and differences of three types of cellular therapies (CAR-T, CAR-NK, and CAR-M) regarding their mechanisms of action, clinical advantages, and technological bottlenecks. We hope that our findings will provide a theoretical basis for optimizing immunotherapeutic strategies for OC. Trial Registration: ClinicalTrials.gov identifier: NCT03585764.
Two isoforms of the 90-kDa heat shock protein (Hsp90), stress-inducible Hsp90α and constitutively expressed Hsp90β, function in mammalian cells as molecular chaperones that promote the folding of specific client proteins involved in essential cellular processes and regulatory pathways. A number of Hsp90 client proteins take part in cancer progression, and the inhibition of Hsp90 induces the degradation of oncogenic client proteins and cancer cell death. Hsp90 inhibitors specific for individual Hsp90 isoforms have a significant potential for the development of anticancer therapeutics due to reduced toxicity. Cells with knocked-out genes encoding Hsp90 isoforms represent excellent cellular models to investigate the rearrangement of the cell chaperone machinery in response to the suppression/loss of the Hsp90 isoforms. Recently, we have shown that the knockout of the HSP90AA1 gene encoding Hsp90α in human fibrosarcoma HT1080 cells does not affect basic cellular processes in normal and stressful conditions, which suggests an adaptation of the cell chaperone machinery to the loss of Hsp90α. Here, we demonstrated that the lack of Hsp90α in HT1080 cells leads to an up-regulation of the constitutively expressed Hsp90β and several important Hsp90 co-chaperones (Aha1, Hop, and others). The expression of the major chaperones of the Hsp70 machinery (Hsp70-1, Hsp70-2, Hsc70) was also significantly induced. The components of the prefoldin-chaperonin folding arm and PFDL, R2TP, and R2SP complexes, as well as the major mitochondrial chaperones, were also largely up-regulated in Hsp90α-KO cells, while the expression of ER-resident chaperones/co-chaperones was either repressed or did not change. We demonstrated here for the first time an adaptation of the cell chaperone machinery to the loss of the Hsp90α chaperone, which may be important for understanding the molecular mechanisms of action of Hsp90α-specific inhibitors and elaborating new therapy strategies in combating cancer, including the combination of Hsp90α-targeted therapy.
To synthesize and evaluate current evidence on the responsiveness, interpretability (MID/MIC), and clinical utility of validated health-related quality of life (HRQoL) patient-reported outcome (PRO) instruments used in adults with head and neck cancer (HNC). A systematic search of PubMed, Scopus, Web of Science, Embase, and Cochrane Library (Central) identified studies published from January 2015 to July 2025. The review was registered in PROSPERO (CRD420251128978) and followed PRISMA 2020 guidelines. Observational and interventional studies assessing HRQoL using validated HNC instruments (EORTC QLQ-C30, QLQ-H&N35/H&N43, UW-QOL, FACT-H&N or MDADI) were included. Eligible studies reported responsiveness (ability to detect meaningful change) or clinical applicability. Methodological quality was evaluated using the COSMIN Risk of Bias checklist, and results were narratively synthesized due to methodological heterogeneity. Thirteen studies involving 8,075 patients met the inclusion criteria. The EORTC QLQ-C30 and H&N35/43, UW-QOL, FACT-H&N, and MDADI exhibited consistent responsiveness, capturing expected HRQoL deterioration during treatment and partial recovery within 6-12 months. Reported minimal important difference (MID) and minimal important change (MIC) values typically ranged from 4 to 15 points for improvement and 10-20 points for deterioration, supporting the interpretability of change scores. Several patient-reported outcome measures (PROMs) also demonstrated prognostic relevance, with early HRQoL changes associated with survival or recurrence. Validated HRQoL questionnaires in HNC demonstrate robust responsiveness and meaningful clinical applicability, supporting their integration into routine oncology practice. Their use may enhance early detection of complications, guide rehabilitative interventions, and facilitate more individualized, patient-centered care.
The morphology of a signet-ring can be imparted by a number of benign and malignant neoplasms. This poses a significant diagnostic pitfall in such cases, owing to deceptive cell cytology, scattered, scant cells, and the accumulation of large cytoplasmic mucin vacuoles, giving the characteristic 'signet ring cell appearance'. Herein, we present a case of embryonal carcinoma in the retroperitoneal region in a 13-year-old girl. Fine needle aspiration cytology can be misleading due to the presence of signet-ring-like cells. We present a rare case of embryonal carcinoma with signet-ring differentiation and its cytohistological correlation.