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Scientific Reports May 2024Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin's lymphoma, for which cyclophosphamide, doxorubicin, vincristine, and prednisone with...
Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin's lymphoma, for which cyclophosphamide, doxorubicin, vincristine, and prednisone with rituximab(R-CHOP) is one of the standard regimens. Given that R-CHOP is highly emetogenic, chemotherapy-induced nausea and vomiting (CINV) prevention is clinically important. However, there is a paucity of studies focusing on these patients. This study aimed to ascertain the effectiveness of an oral fixed-dose combination of netupitant and palonosetron (NEPA) in preventing CINV in patients with DLBCL undergoing first-line R-CHOP chemotherapy. Seventy patients were enrolled in this single-center prospective non-comparative study conducted between November 2020 and May 2023 in South Korea. NEPA was administered 1 h prior to chemotherapy initiation on day 1. The primary endpoint of the study was the complete response rate (no emesis, and no rescue medication) during the acute, delayed, and overall phases, which were assessed over a period of 120 h post-chemotherapy. The complete response rates for NEPA were 90.0% [95% CI 80.5, 95.9] for the acute phase, 85.7% [95% CI 75.3, 92.9] for the delayed phase, and 84.3% [95% CI 73.6, 91.9] for the overall phase, with no-emesis rates (acute: 97.1% [95% CI 97.1, 99.7], delayed: 95.7% [95% CI 88.0, 99.1], overall: 92.9% [95% CI 84.1, 97.6]). NEPA was well tolerated with no severe treatment-emergent adverse events. NEPA exhibited substantial efficacy in mitigating CINV in DLBCL patients undergoing R-CHOP chemotherapy, demonstrating high CR and no-emesis rates, and favorable safety profiles.
Topics: Humans; Lymphoma, Large B-Cell, Diffuse; Antineoplastic Combined Chemotherapy Protocols; Doxorubicin; Cyclophosphamide; Male; Female; Middle Aged; Vincristine; Nausea; Vomiting; Rituximab; Prednisone; Aged; Palonosetron; Adult; Prospective Studies; Antiemetics; Pyridines; Treatment Outcome; Drug Combinations; Isoquinolines; Quinuclidines
PubMed: 38755279
DOI: 10.1038/s41598-024-62057-4 -
Frontiers in Physiology 2024Gregarines are usually classified as parasites, but recent studies suggest that they should be viewed on a parasitism-mutualism spectrum and may even be seen as part of...
Gregarines are usually classified as parasites, but recent studies suggest that they should be viewed on a parasitism-mutualism spectrum and may even be seen as part of the gut microbiota of host insects. As such, they may also impact the consumption of their hosts and/or be involved in the digestion or detoxification of the host's diet. To study such effects of a gregarine species on those traits in its host, the mustard leaf beetle () was used. This beetle species feeds on Brassicaceae plants that contain glucosinolates, which form toxic compounds when hydrolyzed by myrosinases. We cleaned host eggs from gametocysts and spores and reinfected half of the larvae with gregarines, to obtain gregarine-free (G-) and gregarine-infected (G+) larvae. Growth and food consumption parameters of these larvae were assessed by rearing individuals on watercress (, Brassicaceae). A potential involvement of gregarines in the glucosinolate metabolism of larvae was investigated by offering G- and G+ larvae leaf discs of watercress (containing mainly the benzenic 2-phenylethyl glucosinolate and myrosinases) or pea (, Fabaceae, lacking glucosinolates and myrosinases) treated with the aliphatic 4-pentenyl glucosinolate or the indole 1-methoxy-3-indolylmethyl glucosinolate. Larval and fecal samples were analyzed via UHPLC-QTOF-MS/MS to search for breakdown metabolites. Larval development, body mass, growth rate and efficiency to convert food into body mass were negatively affected by gregarine infection while the pupal mass remained unaffected. The breakdown metabolites of benzenic and aliphatic glucosinolates were conjugated with aspartic acid, while those of the indole glucosinolate were conjugated with glutamic acid. Gregarine infection did not alter the larvae's ability to metabolize glucosinolates and was independent of plant myrosinases. In summary, some negative effects of gregarines on host performance could be shown, indicating parasitism. Future studies may further disentangle this gregarine-host relationship and investigate the microbiome potentially involved in the glucosinolate metabolism.
PubMed: 38751987
DOI: 10.3389/fphys.2024.1394576 -
Journal of Investigative Medicine High... 2024Primary cardiac lymphoma is an exceedingly rare malignant tumor, with diffuse large B-cell lymphoma (DLBCL) being the most prevalent histological subtype. This disease...
Primary cardiac lymphoma is an exceedingly rare malignant tumor, with diffuse large B-cell lymphoma (DLBCL) being the most prevalent histological subtype. This disease has non-specific clinical manifestations, making early diagnosis crucial. However, DLBCL diagnosis is commonly delayed, and its prognosis is typically poor. Herein, we report the case of a 51-year-old male patient with DLBCL who presented with recurrent chest tightness for 4 months as the primary clinical symptom. The patient was admitted to the hospital and diagnosed with acute myocardial infarction and left ventricular hypertrophy with heart failure. Echocardiography revealed a progression from left ventricular thickening to local pericardial thickening and adhesion in the inferior and lateral walls of the left ventricle. Finally, pathological analysis of myocardial biopsy confirmed the diagnosis of DLBCL. After treatment with the R-CHOP chemotherapy regimen, the patient's chest tightness improved, and he was discharged. After 2 months, the patient succumbed to death owing to sudden ventricular tachycardia, ventricular fibrillation, and decreased blood pressure despite rescue efforts. Transthoracic echocardiography is inevitable for the early diagnosis of DLBCL, as it can narrow the differential and guide further investigations and interventions, thereby improving the survival of these patients.
Topics: Humans; Lymphoma, Large B-Cell, Diffuse; Male; Middle Aged; Heart Neoplasms; Myocardial Infarction; Echocardiography; Fatal Outcome; Antineoplastic Combined Chemotherapy Protocols; Hypertrophy, Left Ventricular; Vincristine; Doxorubicin; Rituximab; Cyclophosphamide; Prednisone
PubMed: 38747509
DOI: 10.1177/23247096241253334 -
Scientific Reports May 2024The absence of stimulator of interferon genes (STING) in 129.B6.Fcgr2b-deficient mice rescue lupus phenotypes. The administration of a STING inhibitor (ISD017) into the...
The absence of stimulator of interferon genes (STING) in 129.B6.Fcgr2b-deficient mice rescue lupus phenotypes. The administration of a STING inhibitor (ISD017) into the young 129.B6.Fcgr2b-deficient mice prevents lupus nephritis development. This study mainly aimed to evaluate the effects of STING inhibition (ISD107) on established SLE in mice to prove that ISD017 could be a good therapeutic drug to reverse the already set-up autoimmunity and kidney impairment. Twenty-four-week-old Fcgr2b-deficient mice were treated with cyclophosphamide (25 mg/kg, intraperitoneal, once per week), ISD017 (10 mg/kg, intraperitoneal, three times per week), or control vehicle for 8 weeks, and were analyzed for phenotypes. Both ISD017 and cyclophosphamide treatment increased long-term survival and reduced the severity of glomerulonephritis in Fcgr2b-deficient mice. While cyclophosphamide reduced activated B cells (B220GL-7), ISD017 decreased activated T cells (CD4CD69) and neutrophils (Ly6cLy6g) in Fcgr2b-deficient mice. In addition, ISD017 reduced IL-1β and interferon-inducible genes. In summary, ISD017 treatment in symptomatic 129.B6.Fcgr2b-deficient mice reduced the severity of glomerulonephritis and increased long-term survival. ISD017 worked comparably to cyclophosphamide for treating lupus nephritis in 129.B6.Fcgr2b-deficient mice. ISD017 reduced activated T cells and neutrophils, while cyclophosphamide targeted activated B cells. These results suggested that STING inhibitors can potentially be a new therapeutic drug for treating lupus.
Topics: Animals; Mice; Membrane Proteins; Cyclophosphamide; Receptors, IgG; Lupus Nephritis; Glomerulonephritis; Mice, Knockout; Female; Disease Models, Animal; B-Lymphocytes; Lupus Erythematosus, Systemic; Mice, Inbred C57BL
PubMed: 38745067
DOI: 10.1038/s41598-024-61597-z -
Transplant Immunology Jun 2024Premature ovarian failure (POF), also known as primary ovarian insufficiency, is a common endocrine disease in young women. The emergence of regenerative medicine using...
Beneficial effects of human umbilical cord mesenchymal stem cell (HUCMSC) transplantation on cyclophosphamide (CTX)-induced premature ovarian failure (POF) in Tibetan miniature pigs.
BACKGROUND
Premature ovarian failure (POF), also known as primary ovarian insufficiency, is a common endocrine disease in young women. The emergence of regenerative medicine using stem cells may improve ovarian function and structure, and represents a promising prospect for POF treatment. In his study, we explored the therapeutic effects of human umbilical cord mesenchymal stem cell (HUCMSC) transplantation in a Tibetan miniature pig model of cyclophosphamide (CTX)-induced POF.
METHODS
We cultured and identified HUCMSCs, labeled them with DiR iodide red dye, and implanted them into a CTX-induced model of POF in Tibetan miniature pigs. The daily weight changes were recorded, and the levels of estradiol (E2) and follicle-stimulating hormone (FSH) were measured on days 0, 7, and 14. At the end of the 21-day observation period, in vivo imaging of the bilateral ovaries was performed, and the ovarian index was measured. Ovarian tissue morphology and follicles were examined by hematoxylin-eosin staining. The terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay was employed to assess cell apoptosis, and immunohistochemistry was used to determine the levels of p-AKT, p-ERK1/2, BAX, and BCL2 expression.
RESULTS
Our analysis indicated successful delivery of HUCMSCs to the ovaries of the POF pig model. Significant increases were observed in body weight, E2 levels, ovarian index, and number of normal follicles (all p < 0.05). Moreover, FSH levels reduced and ovarian tissue morphology improved following HUCMSCs transplantation (all p < 0.05). Importantly, upregulated p-AKT, p-ERK1/2, and BCL2 expression were observed, whereas the expression of BAX was suppressed (all p < 0.05), suggesting the inhibition of ovarian cell apoptosis.
CONCLUSION
Our study highlights the significant therapeutic effects of HUCMSC transplantation on CTX-induced POF in a Tibetan miniature pig model.
Topics: Animals; Female; Primary Ovarian Insufficiency; Swine; Cyclophosphamide; Swine, Miniature; Mesenchymal Stem Cell Transplantation; Humans; Mesenchymal Stem Cells; Apoptosis; Disease Models, Animal; Umbilical Cord; Cells, Cultured; Estradiol; Ovary
PubMed: 38744348
DOI: 10.1016/j.trim.2024.102051 -
Experimental Dermatology May 2024Limited data exist on the factors associated with hospitalization and mortality in Asian inpatients with autoimmune bullous dermatoses (AIBDs). This study aimed to...
Limited data exist on the factors associated with hospitalization and mortality in Asian inpatients with autoimmune bullous dermatoses (AIBDs). This study aimed to elucidate the risk factors affecting hospitalization and mortality rates in Asian patients with AIBDs. A retrospective analysis of patients with AIBDs treated at Siriraj Hospital during a 17-year period was performed using the International Classification of Diseases 10th revision codes. The characteristics of inpatients and outpatients were compared, and mortality rates and associated factors were identified. The study included 360 AIBD patients (180 inpatients, 180 outpatients). Inpatients were significantly younger than outpatients. The identified risk factors for hospitalization were malignancy (odds ratio [OR] 2.83, 95% confidence interval [CI] 1.13-8.04; p = 0.034), moderate to severe disease (OR 2.52, 95% CI 1.49-4.34; p < 0.001), systemic corticosteroid use ≥15 mg/day (OR 2.27, 95% CI 1.21-4.41; p = 0.013) and oral cyclophosphamide treatment (OR 9.88, 95% CI 3.82-33.7; p < 0.001). Kaplan-Meier analysis revealed mortality rates of 26%, 36% and 39% for inpatients with pemphigus at 1, 3 and 5 years, respectively. For inpatients with pemphigoid, the corresponding rates were 28%, 38% and 47%. Infections, particularly pneumonia, were the predominant cause of death in both conditions. This study confirmed that both Asian ethnicity and healthcare disparities may be correlated with adverse outcomes in patients with AIBDs. Pemphigus mortality rates were substantially greater in Asian patients than in Caucasian patients. Continuous monitoring of factors contributing to hospitalization and mortality is imperative to improve treatment outcomes.
Topics: Humans; Retrospective Studies; Female; Male; Middle Aged; Hospitalization; Aged; Skin Diseases, Vesiculobullous; Autoimmune Diseases; Adult; Risk Factors; Asian People; Cyclophosphamide; Aged, 80 and over; Adrenal Cortex Hormones; Immunosuppressive Agents; Neoplasms; Young Adult; Kaplan-Meier Estimate; Age Factors
PubMed: 38742822
DOI: 10.1111/exd.15095 -
The Journal of the Association of... Jan 2024Peripheral T cell lymphoma (PTCL), not otherwise specified (NOS) is a heterogenous group of predominantly nodal T cell lymphomas that generally presents with...
BACKGROUND
Peripheral T cell lymphoma (PTCL), not otherwise specified (NOS) is a heterogenous group of predominantly nodal T cell lymphomas that generally presents with lymphadenopathy with or without extra nodal involvement. Acral vascular syndrome clinically presents as digital ischemia with Raynaud's phenomenon and acral cyanosis. Although, this condition is commonly associated with connective tissue disorder, smoking and vasculitis, its association with lymphoid malignancy is very rare. Here, we present a case report of a patient with digital gangrene of all toes and fingers as a presenting symptom of PTCL-NOS.
CASE DESCRIPTION
A 62 year old male presented with digital ischemia associated with pain, low grade fever, loss of appetite and significant weight loss of 6 kilograms over a period of 3 months. On examination, he was found to have bilateral inguinal and axillary lymph nodes with gangrenous changes over toes and fingers but peripheral pulses were palpable. On evaluation he had anemia, elevated ESR and CRP. CT angiogram revealed thinned out digital arteries with multifocal areas of narrowing. Patient was screened for other causes of digital gangrene and was tested negative for ANCA, ANA, cryoglobulins and viral markers. Lymph node biopsy with IHC was suggestive of peripheral T-cell lymphoma-NOS and was started on CHOP regimen. Lymph nodes size decreased and gangrenous changes resolved.
CONCLUSION
Though digital ischemia is a rare paraneoplastic presentation of lymphoma, it should be considered if there is a rapid progression of gangrene. Early initiation of chemotherapy may result in the reduction of further progression of digital gangrene and thus prevent permanent disability. In our patient, progression of gangrene was prevented even though it was an aggressive variant of T cell lymphoma.
Topics: Humans; Male; Gangrene; Lymphoma, T-Cell, Peripheral; Middle Aged; Fingers; Paraneoplastic Syndromes; Toes; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Doxorubicin; Vincristine; Prednisone
PubMed: 38736082
DOI: 10.59556/japi.71.0370 -
The Journal of Medical Investigation :... 2024The Common Terminology Criteria for Adverse Events (CTCAE) is used as a tool to evaluate the adverse events (AE) of chemotherapy in cancer patients. Since CTCAE by...
BACKGROUND
The Common Terminology Criteria for Adverse Events (CTCAE) is used as a tool to evaluate the adverse events (AE) of chemotherapy in cancer patients. Since CTCAE by medical providers underestimates AE more than patient-reported outcomes (PRO), the National Cancer Institute developed PRO-CTCAE. The present study investigated differences between symptoms detected using CTCAE by medical providers and PRO-CTCAE by breast cancer patients.
METHODS
Patients received chemotherapy comprising epirubicin and cyclophosphamide pre- or postoperatively. AE were evaluated using 4 questionnaires:PRO-CTCAE, CTCAE, the European Organization for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC-QLQ-30), and Hospital Anxiety and Depression Scale (HADS) after 1, 2, and 3 courses of chemotherapy.
RESULTS
Forty-two patients were registered. Regarding the recognition of psychological symptoms, such as fatigue, anxiety, and discouragement, and subjective symptoms, including heart palpitations and shortness of breath, PRO using PRO-CTCAE was significantly higher than medical provider-recognized outcomes using CTCAE. Concerning the recognition of regimen-specific symptoms, such as vomiting, nausea, and decreased appetite, medical provider- recognized outcomes were the same or higher than PRO. In QLQ-C30, the physical and role functions, fatigue and dyspnea significantly worsened after 2 and 3 courses of chemotherapy. J. Med. Invest. 71 : 82-91, February, 2024.
Topics: Humans; Breast Neoplasms; Female; Middle Aged; Quality of Life; Adult; Aged; Surveys and Questionnaires; Epirubicin; Patient Reported Outcome Measures; Cyclophosphamide; Antineoplastic Agents
PubMed: 38735729
DOI: 10.2152/jmi.71.82 -
Bulletin of Environmental Contamination... May 2024Traffic-related particulate matter emissions have been considerably reduced due to stringent regulations in Europe. However, emission of diesel-powered vehicles still...
Traffic-related particulate matter emissions have been considerably reduced due to stringent regulations in Europe. However, emission of diesel-powered vehicles still poses a significant environmental threat, affecting rural ecosystems and agriculture. Several studies have reported that polycyclic aromatic hydrocarbons (PAHs), a group of potentially toxic organic compounds, can accumulate in crops and vegetables. In our study, white mustard (Sinapis alba L.) plants were experimentally treated with an extract of diesel exhaust. PAH concentrations were measured in the different plant compartments (stems, leaves and seeds), bioconcentration factors (BCFs) were also calculated. Significant accumulation was measured in the leaves and seeds, stems showed lower accumulation potential. All plant matrices showed high tendency to accumulate higher molecular weight PAHs, BCF was the highest in the 6-ring group. The fact that considerable accumulation was experienced in the seeds might show the risk of cultivating crops nearby roads highly impacted by traffic-related emissions.
Topics: Seeds; Polycyclic Aromatic Hydrocarbons; Air Pollutants; Environmental Monitoring; Sinapis; Vehicle Emissions; Particulate Matter
PubMed: 38733550
DOI: 10.1007/s00128-024-03895-w -
Nutrients May 2024Numerous studies have investigated the immunomodulatory effects of yogurt, but the underlying mechanism remained elusive. This study aimed to elucidate the alleviating...
Numerous studies have investigated the immunomodulatory effects of yogurt, but the underlying mechanism remained elusive. This study aimed to elucidate the alleviating properties of yogurt on immunosuppression and proposed the underlying mechanism was related to the metabolite D-lactate. In the healthy mice, we validated the safety of daily yogurt consumption (600 μL) or D-lactate (300 mg/kg). In immunosuppressed mice induced by cyclophosphamide (CTX), we evaluated the immune regulation of yogurt and D-lactate. The result showed that yogurt restored body weight, boosted immune organ index, repaired splenic tissue, recovered the severity of delayed-type hypersensitivity reactions and increased serum cytokines (IgA, IgG, IL-6, IFN-γ). Additionally, yogurt enhanced intestinal immune function by restoring the intestinal barrier and upregulating the abundance of Bifidobacterium and Lactobacillus. Further studies showed that D-lactate alleviated immunosuppression in mice mainly by promoting cellular immunity. D-lactate recovered body weight and organ development, elevated serum cytokines (IgA, IgG, IL-6, IFN-γ), enhanced splenic lymphocyte proliferation and increased the mRNA level of T-bet in splenic lymphocyte to bolster Th1 differentiation. Finally, CTX is a chemotherapeutic drug, thus, the application of yogurt and D-lactate in the tumor-bearing mouse model was initially explored. The results showed that both yogurt (600 μL) and D-lactate (300 mg/kg) reduced cyclophosphamide-induced immunosuppression without promoting tumor growth. Overall, this study evaluated the safety, immune efficacy and applicability of yogurt and D-lactate in regulating immunosuppression. It emphasized the potential of yogurt as a functional food for immune regulation, with D-lactate playing a crucial role in its immunomodulatory effects.
Topics: Animals; Cyclophosphamide; Yogurt; Mice; Lactic Acid; Cytokines; Male; Immunosuppression Therapy; Spleen; Mice, Inbred BALB C; Hypersensitivity, Delayed; Gastrointestinal Microbiome; Lactobacillus; Bifidobacterium
PubMed: 38732641
DOI: 10.3390/nu16091395