Search Results (315)

After first-line therapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), 20–30% of patients with diffuse large B-cell lymphoma (DLBCL) have relapsed or refractory disease. Semi-quantitative volume parameters on [18F]Fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG PET/CT), performed at diagnosis, could represent variables with prognostic influence. We retrospectively analyzed 53 consecutive patients, treated between 2016 and 2022. Semi-quantitative metabolic parameters, assessed by the software LIFEx, included total metabolic tumor volume (TMTV), total lesion glycolysis (TLG), Dmax and DmaxVox. All cases received R-CHOP/CHOP-like regimens with curative intent. The International Metabolic Prognostic Index (IMPI) was low in 43/53 cases (81.1%). CR was achieved in 49/53 patients (92.4%); 7/53 (13.2%) relapsed after achieving a CR. For the entire cohort, 2-year PFS and OS were 84.9% and 90.6%, respectively, while 5-year PFS and OS were 65.5% and 77.6%, respectively. IPI score, B symptoms, TMTV, Dmax and DmaxVox were associated with reduced PFS in an exploratory univariate analysis. IPI score was the only variable for which we found a significant association with reduced OS. In this exploratory analysis in a small, event-limited population, we suggest the baseline, semi-quantitative metabolic parameters of PET/CT at diagnosis could contribute to defining tumor burden and to predict PFS for DLBCL patients. Full article

Transmissible venereal tumor (TVT) is a contagious neoplasm affecting dogs, commonly treated with vincristine sulfate, although this protocol may be associated with adverse effects and the need for multiple therapeutic sessions. In this context, adjuvant therapies have been investigated to optimize clinical outcomes. This study evaluated the effect of conventional and ozonated autohemotherapy on the number of chemotherapy sessions required to achieve complete remission of TVT. Fifteen dogs with a confirmed diagnosis were randomly allocated into three groups: control (vincristine, n = 5), conventional autohemotherapy associated with vincristine (AHTm, n = 5), and ozonated autohemotherapy associated with vincristine (AHTmO₃, n = 5). The animals were evaluated weekly through clinical, cytological, hematological, and biochemical examinations. The primary outcome was the number of sessions required to achieve complete remission. A significant reduction was observed in the AHTm (p = 0.032) and AHTmO₃ (p = 0.008) groups compared to the control group. No differences were found in laboratory parameters. The findings suggest that autohemotherapy, particularly in its ozonated form, may serve as a promising adjuvant strategy. However, studies with larger sample sizes are needed. Full article

Background: Orbital rhabdomyosarcoma (RMS) is the most common primary pediatric malignant orbital tumor, typically curable with chemotherapy and radiation. Data regarding MRI chemotherapy response and long-term ophthalmologic outcomes remain limited in non-cooperative-group settings. Methods: We retrospectively reviewed children with primary orbital RMS treated at King Hussein Cancer Center (2002–2025) with vincristine, actinomycin-D, and cyclophosphamide (VAC). Pre-local-control MRI responses were classified as complete (CR), partial (PR), stable/minor (SD/MR), or progressive disease (PD). Survival and ophthalmologic outcomes were analyzed. Results: Twenty-two patients (median age 5.6 years) were included. All had localized disease (77% low-risk). All received VAC; 20 (91%) received radiotherapy (median 45 Gy). Pre-radiotherapy MRI showed 8 (36%) CR and 11 (50%) PR. Four patients (18%) died. Five-year event-free survival (EFS) and overall survival (OS) were 73% and 84%, respectively. Cataracts developed in 45% of the cohort (50% of irradiated patients) at a median of 39.1 months (range 9.4–95.1). At last assessment, visual acuity was good in 60%, moderate in 25%, and severely impaired in 15%. Conclusions: Excellent survival in orbital RMS is achievable in resource-stratified settings. Induction MRI progressive disease (PD) was associated with poor outcomes in this cohort and may represent an early prognostic signal warranting further validation in larger studies. Furthermore, the documented maximum cataract latency of 95 months suggests that the standard 5-year surveillance window is insufficient. These findings support extending ophthalmologic surveillance beyond the standard 5-year window. We propose, based on our retrospective institutional data, a 10-year functional survivorship framework. Full article

Endometrial carcinoma (EC) with choriocarcinomatous differentiation is an exceptionally rare malignancy for which standardized postoperative treatment strategies are lacking. Herein, we describe two postmenopausal patients with endometrioid carcinoma containing a choriocarcinomatous component. One patient had an EC-dominant tumor with low and rapidly normalized postoperative serum human chorionic gonadotropin (hCG) levels and received paclitaxel plus carboplatin. The other patient had a choriocarcinomatous-dominant tumor with markedly elevated postoperative serum hCG levels and was treated with gestational trophoblastic neoplasia (GTN)-oriented chemotherapy using etoposide, methotrexate, actinomycin D/cyclophosphamide, and vincristine (EMA/CO). Both patients remain disease-free. A review of representative published cases revealed two competing treatment paradigms, EC-oriented and GTN-oriented, applied inconsistently and without unified selection criteria. On the basis of integrated clinicopathological assessment, we propose that postoperative treatment consideration should be guided primarily by dominant tumor biology, rather than the International Federation of Gynecology and Obstetrics stage alone. Tumors with a dominant choriocarcinomatous component accompanied by elevated postoperative serum hCG levels may benefit from GTN-oriented chemotherapy, whereas EC-dominant tumors with low or normalized hCG levels may benefit from EC-oriented regimens. Reassessment of dominant tumor biology using postoperative pathological findings and serum hCG dynamics may provide a pragmatic, decision-support framework for adjuvant treatment consideration in this rare and clinically challenging entity. Full article

The increasing prevalence of cancer in Thailand over the past decade has resulted in a substantial rise in the use of anticancer drugs, which are eventually discharged into municipal wastewater through hospital and domestic effluents. The inability of conventional wastewater treatment systems to completely remove these pharmaceuticals has been widely reported. The continuous release of these emerging anticancer agents into aquatic environments reduces water quality and threatens biodiversity. Even at trace levels, these compounds may act as persistent pollutants capable of impairing ecosystem. This study investigated the occurrence and concentration levels of three widely used chemotherapeutic agents including cyclophosphamide (COP), doxorubicin (DOX), and vincristine (VIN) in Bangkok’s municipal wastewater to evaluate their potential environmental risks. Thirty-two influent and effluent wastewater samples were collected from eight large-scale wastewater treatment plants (WWTPs) from October 2024 to January 2025. Samples were processed using solid-phase extraction (SPE) and analyzed by liquid chromatography–triple quadrupole mass spectrometry (LC–MS/MS). The analytical method demonstrated high precision and reproducibility, with relative standard deviations (%RSD) below the 20% acceptance limit for all compounds. Method accuracy ranged from 81.84% to 107.21%. Results showed the presence of only COP in almost influent and effluent at levels ranging from 0.26 to 2.06 µg/L. In contrast, DOX and VIN levels remained consistently below the limits of quantitation (LOQ) in all WWTP samples. This study establishes the first baseline for COP, DOX, and VIN contamination in Bangkok’s municipal wastewater. Notably, the residue of COP in wastewater suggests that current wastewater treatment facilities in Thailand are insufficient for its removal, posing a potential long-term risk to local aquatic ecosystems. Full article

Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting toxicity affecting 30–40% of patients treated with neurotoxic chemotherapy. Sensory symptoms arise from injury to dorsal root ganglion (DRG) neurons and their axons; yet, the underlying mechanisms remain incompletely understood. While human induced pluripotent stem cell (iPSC)-derived sensory neuron (iSN) monolayers have provided mechanistic insight, they lack the three-dimensional architecture and cellular heterogeneity of native DRG tissue. Here, we generated human iPSC-derived DRG organoids (iDRGOs) containing mixed neuronal and peripheral glial populations and established a quantitative neurite outgrowth assay to model chemotherapy-induced neurotoxicity in a 3D context. iDRGOs from three healthy donors were exposed to bortezomib, vincristine, or paclitaxel. All three drugs caused dose-dependent neurite outgrowth impairment without significant short-term changes in organoid size, consistent with early axonal injury. Vincristine reduced MAP2 levels when normalized to total protein, whereas bortezomib and paclitaxel showed divergent microtubule-associated responses compared to monolayer cultures. The developmental stage significantly influenced the baseline neurite outgrowth, highlighting the need for age standardization. These results establish iDRGOs as a physiologically relevant human platform that complements monolayer models for mechanistic studies and therapeutic screening in CIPN. Full article

Background: Malignant lymphoma is the most common hematological malignancy; however, primary central nervous system lymphoma accounts for only a small percentage of non-Hodgkin lymphoma (NHL). Among these, primary cauda equina lymphoma (CEL) is extremely uncommon. Its rarity and atypical clinical presentation often make diagnosis challenging. Case Presentation: An 80-year-old man presented with progressive gait disturbance, lower-extremity weakness, and numbness. MRI revealed diffuse swelling and homogeneous gadolinium enhancement of the cauda equina at T12–L1; additionally, CSF cytology identified malignant lymphocytes. Open biopsy confirmed a diagnosis of diffuse large B-cell lymphoma. At diagnosis, the patient was classified as Ann Arbor stage IV, and the clinical parameters corresponded to a high-risk International Prognostic Index (IPI) category. The patient received five courses of immunochemotherapy with rituximab, methotrexate, vincristine, and procarbazine (R-MPV), resulting in marked radiological improvement and functional recovery, achieving a complete response. However, consolidation therapy was discontinued as the patient did not wish to continue. Unfortunately, intracranial relapse occurred four months later, and the patient ultimately succumbed to infectious complications. Only 29 cases of primary CEL have been reported. For all cases, a biopsy with histopathological examination is required for a definitive diagnosis. Currently, combined chemotherapy and radiotherapy are considered the standard treatment. This case was diagnosed through nerve biopsy with cauda equina at T12 to L1 levels, and immunochemotherapy successfully reduced the lesion while improving lower extremity function. Conclusions: Despite the considerable burden on patients, nerve biopsy is necessary for primary CEL to obtain a diagnosis and an early therapeutic approach for both neurological and vital prognoses. Full article

Background/Objectives: The aberrant epigenetic landscape of cancer cells has attracted wide attention, motivating the search for new epigenetically active drugs both for anticancer therapy and for overcoming the drug resistance promoted by epigenetic changes. The use of epi-drugs in cancer therapy requires consideration of the influence of applied treatment on epigenetic regulation of gene expression. Therefore, it is reasonable to screen epigenetically active compounds among the drugs widely used in clinical oncology. Methods: We applied the HeLa TI cell-based assay to analyze the epigenetic activity of 40 drugs including 22 chemotherapeutic, 2 immunotherapeutic, 13 targeted, and 3 palliative agents. Reactivation of the epigenetically silenced GFP reporter gene integrated into the genome of HeLa TI cells was assessed using flow cytometry. Results: Statistically significant increases in the proportions of GFP-positive cells were demonstrated for the alkylating agent chlorambucil; the antimetabolites cytarabine, fluorouracil, gemcitabine, and pemetrexed; the platinum-based compounds cisplatin, and oxaliplatin; the topoisomerase inhibitor topotecan; and the antimicrotubule agents docetaxel, vincristine, and eribulin. Epigenetic activity was also detected for the targeted-therapy agents AZD8055, wortmannin, and cetuximab, as well as for the corticosteroid dexamethasone. Thus, epigenetic activity was revealed for 15 drugs widely used in cancer therapy, which possess different modes of action. Conclusions: Our findings show that many anticancer therapy agents modulate the epigenetic landscape of cancer cells, providing a rationale for expanding their therapeutic applications and enhancing the efficacy of combination strategies by overcoming epigenetically driven chemoresistance. Full article

Background and Clinical Significance: We report a rare case of a 66-year-old male with malignant non-germinal center-type large B-cell lymphoma involving the thoracic epidural, cauda equina, and filum terminal simultaneously. Case Presentation: The patient complained of back pain, rapid progressive numbness, and motor palsy in both legs in one month. Neurological examination revealed grade 2 muscle power in both lower limbs, hypesthesia below the T8 dermatome, and bladder and bowel dysfunctions. Magnetic resonance imaging (MRI) with contrast showed a well-defined extradural lesion extending from the T7 to T9 level, with severe spinal cord compression. Additionally, it revealed enlargement of the cauda equina occupying the extradural space from the L1-S1 level. The lesion appeared isointense on T1, mildly hyperintense on T2-weighted images, and exhibited homogeneous enhancement on post-contrast images. To relieve the patient’s spinal cord compression as soon as possible and allow the patient to recover quickly after surgery, we performed unilateral biportal endoscopy (UBE) to completely remove the T7-9 epidural lesion. The immunohistochemical assessment confirmed a histological diagnosis of diffuse large B-cell lymphoma, a non-germinal center type. The patient received radiotherapy to the thoracic and lumbosacral areas (50 Gy) and chemotherapy with six cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) after surgery. Follow-up positron emission tomography (PET) scan and MRI performed 4 months after surgery revealed complete remission of the lesion. The patient was able to walk using a walker after therapy. Conclusions: UBE is a favorable option for selected patients requiring immediate chemotherapy or radiotherapy owing to its reduced tissue trauma compared to traditional open surgery. Full article

Continuous monocropping of cassava (Manihot esculenta Crantz) often leads to soil degradation and yield decline, commonly referred to as continuous cropping obstacles (CCOs), which are closely linked to changes in soil physicochemical properties and microbial communities. Biochar has been widely used as a soil amendment to improve soil quality and microbial activity and is considered a potential strategy for alleviating CCOs. Understanding the effects of biochar on soil bacteria and metabolites under field conditions is essential, as it provides insights into its practical effectiveness in reducing CCOs and improving soil health in cassava cultivation systems. In this study, a field experiment was conducted in a continuous cassava system to investigate the effects of a single biochar application rate on soil bacterial diversity, community composition, and metabolite profiles in both rhizosphere and bulk soils. High-throughput 16S rRNA gene sequencing and UHPLC–MS/MS-based non-targeted metabolomics were employed to analyze soil bacterial and metabolic patterns. Biochar was associated with increased α-diversity in rhizosphere soil and distinct shifts in β-diversity. Biochar increased the relative abundance of Chloroflexi and Actinobacteriota in the bulk soil, while Cyanobacteria and Nitrospirota were more abundant in the rhizosphere. Network analysis revealed the compartment-specific differences after biochar application, with higher network complexity in the rhizosphere and lower complexity in the bulk soil relative to the control. Metabolomic profiling identified 402 metabolites in positive ion mode and 357 in negative ion mode. In the rhizosphere, biochar-treated soil exhibited higher relative abundances of alkaloids (e.g., trigonelline, berberine, vincristine) and flavonoids (e.g., catechin, naringin, rutin, and taxifolin), which are commonly linked to plant stress responses. In the bulk soil, biochar application resulted in lower levels of several anthropogenic organic compounds (e.g., monobutyl phthalate, terephthalic acid, and p–toluenesulfonic acid). These findings provide preliminary field evidence that biochar application can lead to compartment-specific changes in soil bacterial communities and metabolite profiles. Such changes are closely related to soil quality and nutrient cycling, pointing to a possible role of biochar in mitigating soil degradation under continuous cassava cultivation. Full article

Chemotherapy-induced neuropathic pain (CINP) can be caused by several chemotherapeutic drugs, including paclitaxel, oxaliplatin, and vincristine, which is difficult to treat with several drugs, including antidepressants and anticonvulsants. The patho-mechanisms of CINP are not completely understood. However, they showed oxidative stress, mitochondrial damage, ion channel damage, and immunological dysfunction. Acting as a key regulator of antioxidant responses, nuclear factor erythroid 2-related factor 2 (Nrf2) decreased oxidative stress and mitochondrial damage. In addition, it plays a role in inhibiting nuclear factor kappa B (NF-κB). A systematic, English-only search of MEDLINE (PubMed) was performed for studies on Nrf2, chemotherapy, and neuropathic pain from database inception through 1 December 2024. Several Nrf2 activators, including tempol, oltipraz, rosiglitazone, pristimerin, cannabidiol, daidzein, bardoxolone methyl, curcumin, resveratrol, and mitoquinone, demonstrated analgesic effects in CINP animal models. Furthermore, in clinical studies, curcumin demonstrated significant efficacy in reducing vincristine-induced neuropathy in pediatric leukemia patients, while the combined administration of alpha-lipoic acid with ipidacrin hydrochloride prevented paclitaxel-induced motor neuropathy and improved axonal function in breast cancer patients. Thus, the purposes of our review article were to summarize the analgesic effects of Nrf2 activators and the patho-mechanisms of Nrf2 in CINP animal, and then the consequences for clinical trials were presented. Full article

Background: Diffuse leptomeningeal glioneuronal tumors (DLGNT) are rare pediatric central nervous system tumors, first recognized in the 2016 WHO classification. Their clinical course is highly heterogeneous, and no international consensus treatment guidelines are currently available. This study aims to describe clinical characteristics, disease evolution, and management strategies for pediatric DLGNT patients, with a focus on aggressive forms. Methods: This retrospective, multicenter, international study (Belgium and France) included pediatric patients diagnosed with DLGNT between 1 February 2016 and 31 December 2024. Clinical, radiological, histopathological, molecular, and therapeutic data were collected. Findings were analyzed and contextualized through an extensive literature review. Results: Eleven patients were enrolled (median age: 8.2 years; median follow-up: 52 months). The median delay between the first MRI and definitive diagnosis was 6.5 months. Symptoms of intracranially elevated pressure were present in 55% of patients. Two-thirds of the patients presented with leptomeningeal dissemination at diagnosis. The primary tumor site could not be identified in two patients. A KIAA1549::BRAF transcript fusion was detected in 82% of cases, and chromosome 1q gain in 38%. All patients underwent surgery at diagnosis. The median number of therapeutic lines was four: 82% received chemotherapy (weekly vinblastine in 55%, vincristine/carboplatin regimen in 45%), 64% received MAPK pathway-targeted therapy, and 18% underwent radiotherapy. Five-year overall survival (OS) was 68.5%, and median progression-free survival (PFS) was 5.3 months after first-line therapy and 16.5 months after the second line. At the end of follow-up, only one patient achieved complete remission, and 78% of survivors presented with persistent neurological deficits. Conclusions: This study underscores the significant diagnostic delay, clinical heterogeneity, and absence of standardized therapeutic approaches in pediatric DLGNT patients. Conventional low-grade glioma chemotherapy constitutes the current treatment backbone, while MAPK pathway-targeted therapies show promising potential. Further studies and the establishment of an international registry are crucial to better characterize aggressive subtypes and optimize management strategies. Full article

Background/Objectives: Preclinical models that accurately reflect Ewing sarcoma (ES) will enable the prioritisation of clinically active targeted agents from bench to clinic. To expedite this process, we have established and characterised patient-derived ES cultures (PDES) in vitro. Methods: Fluorescence in situ hybridisation, RT-PCR and western blotting were used to examine expression of the pathognomonic EWSR1 fusions. Activation or repression of EWSR1 fusion downstream targets and proliferation was examined by immunofluorescence and immunohistochemistry. Using next-generation sequencing, the DNA and transcriptomic profiles of PDES and cell lines were compared. The response of PDES and cell lines to standard-of-care chemotherapeutics, ionising radiation and investigational drugs was examined. Results: All PDES contain EWSR1 fusion DNA, consistent with a diagnosis of ES. EWSR1 fusion gene RNA and protein were detected in 70% and 21% of PDES, respectively. Markers of proliferation and expression of EWSR1 fusion target genes were consistent with the tumours from which PDES were derived (R² = 0.74, p < 0.0001) and the paediatric mesenchymal lineage (SBS5 and SBS1, ID1 and ID2). In contrast, the transcriptome of PDES was significantly different from that of cell lines. PDES had a significantly increased doubling time (p < 0.00001), decreased expression of Ki67 (p < 0.0001) and increased migration (p < 0.02) compared to cell lines. Consistent with the longer doubling time, PDES were more resistant to doxorubicin, etoposide and vincristine and ionising radiation (p < 0.0001) than cell lines. PDES were sensitive to mTKIs (cabozantinib, lenvatinib, and regorafenib), and trabectedin. The response of PDES to drugs in vitro reflects the clinical experience of patients. Conclusions: Models incorporating PDES cells may positively contribute to the preclinical pipeline. Full article

Primary effusion-based lymphomas are uncommon and may pose significant diagnostic challenges. Fluid overload-associated large B-cell lymphoma is a recently recognized entity in the 5th edition of the World Health Organization Classification of Hematolymphoid Tumors and should be included in the differential diagnosis of effusion-based lymphomas, particularly in elderly immunocompetent patients with conditions that predispose to fluid overload. Background and Clinical Significance: We report a case of fluid overload-associated large B-cell lymphoma to add to the limited literature and highlight distinguishing features from other primary effusion lymphomas. Case Presentation: A 77-year-old male with end-stage renal disease on hemodialysis and heart failure with reduced ejection fraction was admitted for respiratory failure and found to have a right-sided pleural effusion. Two pleural fluid specimens examined several weeks apart revealed sheets of large atypical lymphoid cells positive for CD20, Pax-5, CD79a, CD45, MUM1, BCL2, BCL6 (weak) and negative for TTF1, CD68, MOC31, BER EP4, WT1, Calretinin, CD3, CD138, CD30, and cMYC. Human Herpesvirus-8 and Epstein–Barr virus were negative. Staging showed a few mildly fluorodeoxyglucose-avid mediastinal lymph nodes which were benign. Ultimately, the patient was diagnosed with fluid overload-associated large B-cell lymphoma and treated with rituximab, cyclophosphamide, vincristine sulfate, and prednisone, but passed away three months after diagnosis. Conclusions: Fluid overload-associated large B-cell lymphoma is a new and important diagnostic consideration in effusion-based lymphomas. It may be mistaken for other conditions such as primary effusion lymphoma or other diffuse large B-cell lymphomas. The presence of a Human Herpesvirus-8-negative effusion-based lymphoma in an elderly immunocompetent patient without nodal or tissue involvement should prompt consideration of fluid overload-associated large B-cell lymphoma. Full article

Chemotherapy is known to cause significant neutropenia, though concomitant left shift (also known as bandemia) has yet to be documented in dogs. The objective of this study is to assess the prevalence of band neutrophil elevation in dogs undergoing multiagent chemotherapy and identify factors influencing bandemia development. Medical records were retrospectively reviewed between 2018 and 2022 for dogs that started multiagent chemotherapy with at least one follow-up visit. Records were analyzed for body surface area (BSA), white blood cell count, segmented neutrophil count, band neutrophil count, and the previously administered chemotherapy drug (vincristine, cyclophosphamide, or doxorubicin). A generalized linear mixed model was used for statistical analysis. Ninety dogs with 530 nadir complete blood counts (CBCs) were identified. Band neutrophils were present in 20.2% of nadir CBCs, and increased band neutrophils occurred in 13.6%. Smaller BSA was associated with higher bandemia prevalence. Bandemia prevalence was 6% higher after vincristine (Risk Difference, 95% CI = [1%, 11%], p = 0.026) or doxorubicin (Risk Difference, 95% CI = [−1%, 13%], p = 0.115) administration than when patients received cyclophosphamide. Limitations include a lack of standardization of protocol, evaluation of underlying conditions that could contribute to bandemia, and opportunity for laboratory error. This study demonstrates that band neutrophils are present in dogs receiving chemotherapy, with a negative relationship between bandemia and BSA. Bandemia was most common following vincristine and doxorubicin administration. Full article