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Oncology Reports Mar 2021Non‑Hodgkin lymphoma (NHL) is a form of lymphoid malignancy, with diffuse large B cell lymphoma (DLBCL) being the most common NHL isoform. Approximately half of... (Observational Study)
Observational Study
Non‑Hodgkin lymphoma (NHL) is a form of lymphoid malignancy, with diffuse large B cell lymphoma (DLBCL) being the most common NHL isoform. Approximately half of patients with DLBCL are successfully cured via first‑line Rituximab, Cyclophosphamide, Epirubicin, Vindesine, Prednisolone (R‑CHOP) treatment. However, 30‑40% of patients with DLBCL ultimately suffer from treatment‑refractory or relapsed disease. These patients often suffer from high mortality rates owing to a lack of suitable therapeutic options, and all patients are at a high risk of serious treatment‑associated dose‑dependent toxicity. As such, it is essential to develop novel treatments for NHL that are less toxic and more efficacious. Oncolytic Vaccinia virus (OVV) has shown promise as a means of treating numerous types of cancer. Gene therapy strategies further enhance OVV‑based therapy by improving tumor cell recognition and immune evasion. Beclin1 is an autophagy‑associated gene that, when upregulated, induces excess autophagy and cell death. The present study aimed to develop an OVV‑Beclin1 therapy capable of inducing autophagic tumor cell death. OVV‑Beclin1 was able to efficiently kill NHL cells and to increase the sensitivity of these cells to R‑CHOP, thereby decreasing the dose‑dependent toxic side effects associated with this chemotherapeutic regimen. The combination of OVV‑Beclin1 and R‑CHOP also significantly improved tumor growth inhibition and survival in a BALB/c murine model system owing to the synergistic induction of autophagic cell death. Together, these findings suggest that OVV‑Beclin1 infection can induce significant autophagic cell death in NHL, highlighting this as a novel means of inducing tumor cell death via a mechanism that is distinct from apoptosis and necrosis.
Topics: Aged; Aged, 80 and over; Animals; Antineoplastic Combined Chemotherapy Protocols; Autophagic Cell Death; Beclin-1; Biopsy; Cell Line, Tumor; Combined Modality Therapy; Cyclophosphamide; Doxorubicin; Female; Genetic Engineering; Humans; Lymphoma, Large B-Cell, Diffuse; Male; Mice; Middle Aged; Oncolytic Virotherapy; Oncolytic Viruses; Prednisone; Rituximab; Tumor Escape; Vaccinia virus; Vincristine; Vindesine; Xenograft Model Antitumor Assays
PubMed: 33469679
DOI: 10.3892/or.2021.7942 -
Frontiers in Oncology 2022mutations are associated with poor prognosis in the vast majority of cancers. In this study, we present a pediatric B-cell acute lymphoblastic leukemia (B-ALL) patient...
mutations are associated with poor prognosis in the vast majority of cancers. In this study, we present a pediatric B-cell acute lymphoblastic leukemia (B-ALL) patient carrying a rare c.C275T mutation. This extremely rare mutation affects an amino acid residue located between the TAD domain and the DNA-binding domain of p53. The patient was resistant to most conventional chemotherapy regimens and remained minimal residual disease (MRD)-positive after five rounds of such regimens. We tested the sensitivity of the patient's leukemic cells to 21 anti-cancer drugs by performing drug sensitivity assays. The results showed that bortezomib had a very strong killing effect on the patient's leukemic cells. Therefore, we subsequently treated the patient with bortezomib combined with vindesine, cytarabine, and fludarabine. After one course of treatment, the patient became MRD-negative, and there was no recurrence during a 9-month follow-up. In conclusion, our report suggests that the c.C275T mutation is associated with poor prognosis in B-ALL. Fortunately, bortezomib combined with chemotherapy could achieve a better therapeutic effect than conventional regimens in this type of ALL.
PubMed: 36798689
DOI: 10.3389/fonc.2022.1018250 -
Zhonghua Xue Ye Xue Za Zhi = Zhonghua... Jun 2015To evaluate the efficacy and safety of recombinant human thrombopoietin (rhTPO) in treatment of pediatric primary immune thrombocytopenia (ITP).
OBJECTIVE
To evaluate the efficacy and safety of recombinant human thrombopoietin (rhTPO) in treatment of pediatric primary immune thrombocytopenia (ITP).
METHODS
The clinical characteristics of 41 pediatric ITP patients who received rhTPO therapy from December 2006 to September 2014 were retrospectively analyzed (as rhTPO group). During the same time another 26 pediatric ITP patients who received vindesine combined with human immunoglobulin therapy were selected as control group. The treatment outcomes were evaluated.
RESULTS
A total of 67 cases of pediatric ITP, 31 males and 36 females with a median age 10.0(1.6-17.0) years were enrolled, including 19 cases of newly disgnosed ITP, 18 cases of persistent ITP and 30 cases of chronic ITP. Of them, 43 cases of whom were severe ITP (PLT<10×10⁹/L). The total response rate had no statistically significant difference between the rhTPO group and the control group (68.29% vs 65.38%, P=0.806), neither in newly ITP, persistent and chronic ITP (P=0.320, P=0.763). In severe ITP patients, 17 of 30 cases (56.67%) achieved response with rhTPO therapy, while the control group was 61.54% (8/13) (P=0.766). The median maximum peak of platelet counts and the time of the platelet counts >30×10⁹/L and > 50×10⁹/L had no statistically significant differences in rhTPO group compared with the control group [52(7-608)×10⁹/L vs 40(3-152)×10⁹/L, P=0.05; 7(3-13) d vs 4(2-24) d, P=0.202; 7.5(4-15) d vs 5.5(4-23) d, P=0.557]. The mean platelet counts were 43(3-605)×10⁹/L in the rhTPO group, which were higher than the control group [32(-14-149)×10⁹/L, P=0.042]. No severe adverse effects were observed in both groups.
CONCLUSION
For pediatric ITP, rhTPO has a similar outcomes with vindesine combined with human immunoglobulin, and it is an effective and safe treatment option.
Topics: Adolescent; Child; Child, Preschool; Female; Humans; Infant; Male; Platelet Count; Purpura, Thrombocytopenic, Idiopathic; Recombinant Proteins; Retrospective Studies; Thrombopoietin; Treatment Outcome; Vindesine
PubMed: 26134019
DOI: 10.3760/cma.j.issn.0253-2727.2015.06.014 -
Medicine Feb 2020The specific pathogenesis of the diffuse large B-cell lymphoma(DLBCL)is still indefinite and argumentative. It is known that DLBCL is the most common type of...
RATIONALE
The specific pathogenesis of the diffuse large B-cell lymphoma(DLBCL)is still indefinite and argumentative. It is known that DLBCL is the most common type of non-Hodgkin's lymphomas (NHL). A lot of cases of DLBCL such as primary gastric diffuse large B-cell lymphoma(PG-DLBCL) are reported. However, primary intestinal diffuse large B-cell lymphoma(PI-DLBCL) is unusual.
PATIENT CONCERNS
We present a case of a 57-year-old male diagnosed in the Gastroenterology Department, which presented a bleeding duodenal ulcer with irregular borders.
DIAGNOSES
The immunohistochemical staining showed: CD20(+++), CD10(+) and Ki-67>40%.
INTERVENTIONS
The patient was successfully treated by Poly-chemotherapy with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vindesine and prednisolone).
OUTCOMES
After 6 courses of chemotherapy treatment, the duodenal ulcer was completely healed by reviewing the UGIE.
LESSONS
Our report might give further strength to avoiding the erroneous and missed diagnosis for PI-DLBCL which is different from common duodenal ulcer.
Topics: Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Diagnosis, Differential; Doxorubicin; Duodenal Ulcer; Humans; Immunohistochemistry; Intestinal Neoplasms; Lymphoma, Large B-Cell, Diffuse; Male; Middle Aged; Prednisone; Rituximab; Vincristine
PubMed: 32028388
DOI: 10.1097/MD.0000000000018590 -
Medicine Nov 2018Post transplantation lymphoproliferative disorder (PTLD) is a rare but severe complication. Epstein-Barr virus (EBV) is considered an important pathogen for PTLD and EBV...
RATIONALE
Post transplantation lymphoproliferative disorder (PTLD) is a rare but severe complication. Epstein-Barr virus (EBV) is considered an important pathogen for PTLD and EBV deoxyribonucleic acid (DNA) load is widely monitored to detect PTLD early. Hepatitis B virus (HBV) infection is rarely reported to be related with PTLD. We report a case of EBV negative (EBV), HBV positive (HBV) diffuse large B cell lymphoma in a patient 12 years after liver transplantation.
PATIENT CONCERNS AND DIAGNOSIS
A 52-year-old man complained of worsening appetite, abdominal distension, and pruritus. Abdominal computed tomography (CT) detected a huge retroperitoneal mass and pathology of the fine needle biopsy established the diagnosis of diffuse large B cell lymphoma. Virology showed active hepatitis B viral duplication and EBV DNA was negative.
INTERVENTION
Treatment modalities for this patient included: reduction and subsequent cessation of immunosuppression; antiviral therapy for HBV with entecavir and adefovir; conventional chemotherapy consisting of cyclophosphamide, epirubicin, vindesine, and prednisone, followed by radiotherapy. He achieved complete remission (CR) and was kept on entecavir treatment afterwards.
OUTCOMES
He has been in remission for 2 years.
LESSONS
HBV infection might have played some role in this very late onset EBV PTLD patient. Therefore, HBV serology and HBV load should be monitored during the follow-up of HBV surface antigen positive (HBsAg) transplant recipients and life-long antiviral therapy is required.
Topics: Adenine; Antiviral Agents; Biopsy, Fine-Needle; Chemoradiotherapy; Guanine; Hepatitis B; Hepatitis B virus; Humans; Immunosuppressive Agents; Liver Transplantation; Lymphoma, Large B-Cell, Diffuse; Male; Middle Aged; Organophosphonates; Tomography, X-Ray Computed; Treatment Outcome; Virus Replication
PubMed: 30383683
DOI: 10.1097/MD.0000000000013063 -
Medical Science Monitor : International... Jan 2019BACKGROUND Esophageal cancer causes considerable mortality and is ranked as the 6th most prevalent type of cancer across the world. At present, there is no effective...
Phillygenin Exerts In Vitro and In Vivo Antitumor Effects in Drug-Resistant Human Esophageal Cancer Cells by Inducing Mitochondrial-Mediated Apoptosis, ROS Generation, and Inhibition of the Nuclear Factor kappa B NF-κB Signalling Pathway.
BACKGROUND Esophageal cancer causes considerable mortality and is ranked as the 6th most prevalent type of cancer across the world. At present, there is no effective esophageal cancer chemotherapy without adverse effects. Moreover, emergence of drug resistance among cancer is another obstacle in the treatment of esophageal cancer. Novel molecules of plant origin may prove beneficial in the development of chemotherapy for esophageal carcinoma. In this study we examined the anticancer effects of phillygenin against the vindesine-resistant esophageal cancer cell line SH-1-V1. MATERIAL AND METHODS The proliferation rate of SH-1-V1 cells was determined by WST-1 assay. Apoptosis was confirmed by propidium iodide (PI) staining. Cell cycle analysis, ROS, and MMP determination were performed by flow cytometery. Protein expression was assessed by Western blot analysis. RESULTS We found that phillygenin inhibited the growth of SH-1-V1 cells and exhibited an IC50 of 6 µM. Investigation of the underlying mechanism revealed that phillygenin triggered apoptotic cell death of the SH-1-V1 cells, which was also associated with enhancement of Bax expression and decreased expression of Bcl-2. Moreover, the expression of cleaved caspase 3 and 9 also increased upon phillygenin treatment. Phillygenin also caused a significant increase in ROS production, concomitant with decreased MMP levels. Phillygenin also caused arrest of cells in the G2/M phase of the cell cycle. In vivo evaluation of phillygenin revealed that it can inhibit tumor weight and volume, suggesting the anticancer potential of phillygenin. CONCLUSIONS In brief, phillygenin inhibited in vitro and in vivo cancer cell growth in drug-resistant human esophageal cancer cells, and these effects were mediated via apoptosis, ROS generation, mitochondrial membrane potential loss, and activation of the NF-kB signalling pathway.
Topics: Apoptosis; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Cell Survival; Esophageal Neoplasms; Humans; Inhibitory Concentration 50; Lignans; Membrane Potential, Mitochondrial; Mitochondria; NF-kappa B; Reactive Oxygen Species; Signal Transduction
PubMed: 30681987
DOI: 10.12659/MSM.913138 -
Frontiers in Immunology 2020CD19 chimeric antigen receptor T cell (CD19CAR-T) has shown great potential to treat acute B cell lymphoblastic leukemia (B-ALL) and B cell lymphoma, and most of...
Case Report: Humanized Selective CD19CAR-T Treatment Induces MRD-Negative Remission in a Pediatric B-ALL Patient With Primary Resistance to Murine-Based CD19CAR-T Therapy.
BACKGROUND
CD19 chimeric antigen receptor T cell (CD19CAR-T) has shown great potential to treat acute B cell lymphoblastic leukemia (B-ALL) and B cell lymphoma, and most of anti-CD19 scFv are derived from murine antibody sequences. However, about 10-20% of B-ALL patients exhibit primary resistance to murine-based CD19CAR-T (CD19mCAR-T). Herein, we report that a humanized selective CD19CAR-T (CD19hsCAR-T) may offer a solution to this problem.
CASE DESCRIPTION
A 10-year old boy was diagnosed with high-risk B-ALL in Mar., 2013, and relapsed in Oct., 2018, after he underwent haplo-identical hematopoietic stem cell transplantation (HSCT) in 2017. The patient then received haplo-identical CD19mCAR-T infusions twice following induction chemotherapy with Vincristine, Dexamethasone and Asparaginase (VDL), but no response was observed. We further treated this patient with CD19hsCAR-T following chemotherapy with Vindesine, Idarubicin, Dexamethasone, and Pegylated Asparaginase (VDLD) plus bortezomib. The patient achieved minimal residual disease-negative (MRDneg) complete remission with incomplete hematopoietic recovery (CRi), and remained in CRi for more than 8 months with manageable side effect. The patient, unfortunately, died of unidentified pulmonary infection on Jan. 25 2020.
CONCLUSION
CD19hsCAR-T may have the potential to induce remission in patients who are primarily refractory to CD19mCAR-T.
Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Child; Combined Modality Therapy; Cytokine Release Syndrome; Cytokines; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Immunotherapy, Adoptive; Male; Mice; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Receptors, Chimeric Antigen; Remission Induction; Salvage Therapy
PubMed: 33424835
DOI: 10.3389/fimmu.2020.581116 -
Journal of the International AIDS... 2014Concomitant use of combination antiretroviral regimen (cART) and cancer chemotherapy is difficult due to complex interactions and increased toxicity. Raltegravir could...
INTRODUCTION
Concomitant use of combination antiretroviral regimen (cART) and cancer chemotherapy is difficult due to complex interactions and increased toxicity. Raltegravir could be an adequate option through its favourable drug-drug interaction profile.
METHODS
Prospective longitudinal study of HIV patients with cancer, AIDS related or not, undergoing chemotherapy. Patients without resistance or previous failure were switched or initiated raltegravir plus two nucleoside analogues. Plasma trough levels of raltegravir were measured.
RESULTS
Overall, 28 patients receiving a raltegravir-based regimen (4 naive) with tenofovir-emtricitabine (18 cases) or abacavir-lamivudine (10 cases) were included. Mean age was 46.2 years (IQR, 39-52.7), and 79% were male. Median time of HIV was 201.7 months, CD4+ nadir was 268 cells/mm(3), and 75% had previous AIDS. At the diagnosis of neoplasia, 17 were on protease inhibitors and 4 with efavirenz. Ten patients had a non-HIV-related cancer (three breast, two pancreatic, one Ewing sarcoma, one myeloblastic leukemia, one melanoma, one parotid adenocarcinoma, one lung), and 18 had an HIV-related cancer (nine non-Hodgkin lymphoma, seven Hodgkin disease, two anal). Overall, 43% of patients received more than one line of chemotherapy, including antimetabolites in 12 patients (5-FU, capecitabine, methotrexate, gemcitabine), alkylating agents in 12 cases (ciclophosphamide, iphosphamide), vinca alkaloids in 20 patients (vincristine, vinblastine, vindesine), antitumor antibiotics in 16 cases (adriamycin), cisplatin o carboplatin in six and monoclonal antibodies in six patients (rituximab, trastuzumab, cetuximab). Six patients modified the doses of antineoplastic agents due to toxicity (four neutropenia), not related to raltegravir. During a median follow up of 12.7 patients-year in concomitant therapy, there was only 1 case of virological failure and no patient discontinued raltegravir. Plasma concentrations of raltegravir in eight patients showed a median concentration of 143 ng/mL (79-455). Four patients (14%) died during the study, not related to AIDS progression. Raltegravir was continued after chemotherapy in all the cases.
CONCLUSIONS
A raltegravir-based therapy is safe and effective in HIV patients undergoing antineoplastic chemotherapy, regardless of the type of tumour, and type and duration of chemotherapy. Pharmacokinetic data show adequate raltegravir levels.
PubMed: 25394095
DOI: 10.7448/IAS.17.4.19590 -
Open Medicine (Warsaw, Poland) 2016Primary pulmonary diffuse large B-cell lymphoma (PPDLBCL) is extremely rare. Its clinical symptoms and signs are nonspe cific, and imaging features also have not yet...
Primary pulmonary diffuse large B-cell lymphoma (PPDLBCL) is extremely rare. Its clinical symptoms and signs are nonspe cific, and imaging features also have not yet been well-defined. Further description is important for the diagnosis and treatment of PPDLBCL. Herein, we reported a case of a patient who suffered from bilateral chest pain and dyspnea. Computed tomography (CT) of chest demonstrated bilateral lung mass, consolidations and reverse halo sign, while consolidations and reverse halo sign are uncommon according to previous reports. Tissue samples were taken by CT guided needle biopsy. The histological samples showed PPDLBCL. This case was special in view of positive expression of CD5. After the case was treated by cyclophosphamide pirarubicin vindesine dexamethasone (CHOP) chemotherapy for six courses, her clinical symptoms were partially alleviated, while CT showed progression disease. This case report highlights different imaging features and characteristics of molecular biology, and reviews study progress of PPDLBCL.
PubMed: 28352766
DOI: 10.1515/med-2016-0010 -
British Journal of Haematology Jun 2015This multicentre, randomized, phase II study was conducted to examine whether the addition of mogamulizumab, a humanized anti-CC chemokine receptor 4 antibody, to... (Randomized Controlled Trial)
Randomized Controlled Trial
This multicentre, randomized, phase II study was conducted to examine whether the addition of mogamulizumab, a humanized anti-CC chemokine receptor 4 antibody, to mLSG15, a dose-intensified chemotherapy, further increases efficacy without compromising safety of patients with newly diagnosed aggressive adult T-cell leukaemia-lymphoma (ATL). Patients were assigned 1:1 to receive mLSG15 plus mogamulizumab or mLSG15 alone. The primary endpoint was the complete response rate (%CR); secondary endpoints included the overall response rate (ORR) and safety. The %CR and ORR in the mLSG15-plus-mogamulizumab arm (n = 29) were 52% [95% confidence interval (CI), 33-71%] and 86%, respectively; the corresponding values in the mLSG15 arm (n = 24) were 33% (95% CI, 16-55%) and 75%, respectively. Grade ≥ 3 treatment-emergent adverse events, including anaemia, thrombocytopenia, lymphopenia, leucopenia and decreased appetite, were observed more frequently (≥10% difference) in the mLSG15-plus-mogamulizumab arm. Several adverse events, including skin disorders, cytomegalovirus infection, pyrexia, hyperglycaemia and interstitial lung disease, were observed only in the mLSG15-plus-mogamulizumab arm. Although the combination strategy showed a potentially less favourable safety profile, a higher %CR was achieved, providing the basis for further investigation of this novel treatment for newly diagnosed aggressive ATL. This study was registered at ClinicalTrials.gov, identifier: NCT01173887.
Topics: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Cyclophosphamide; Disease Progression; Doxorubicin; Etoposide; Female; Humans; Leukemia-Lymphoma, Adult T-Cell; Male; Middle Aged; Nitrosourea Compounds; Prednisolone; Treatment Outcome; Vincristine; Vindesine
PubMed: 25733162
DOI: 10.1111/bjh.13338