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  1. Tang ASO, Ahmad Asnawi AW, Koh AZY, Chong SL, Liew PK, Selvaratnam V, et al.
    Am J Case Rep, 2023 Mar 08;24:e938868.
    PMID: 36882990 DOI: 10.12659/AJCR.938868
    BACKGROUND Plasma cell leukemia (PCL) is an aggressive form of plasma cell neoplasm. We report the first case of primary PCL successfully treated with upfront novel agents consisting of Venetoclax and daratumumab in combination with intensive chemotherapy and allogeneic transplantation. CASE REPORT A 59-year-old woman presented with epistaxis, gum bleeding, and blurred vision. On examination, she appeared pale, with multiple petechiae and hepatomegaly. Fundoscopy revealed retinal hemorrhages. Laboratory investigations revealed bicytopenia and leukocytosis, with mild coagulopathy and hypofibrinogenemia. Elevated globulin and calcium levels were also observed. Serum protein electrophoresis demonstrated IgG lambda paraproteinemia, with a serum-free light chain kappa-to-lambda ratio of 0.074. A skeletal survey revealed the presence of lytic lesions. Bone marrow investigations confirmed the presence of lambda-light-chain-restricted clonal plasma cells. FISH detected t(11;14) and 17p13.1 deletion. Therefore, a final diagnosis of primary PCL was made. The patient received 1 cycle of bortezomib, cyclophosphamide, and dexamethasone (VCD) and 5 cycles of Venetoclax-VCD, followed by an unsuccessful stem cell mobilization. One cycle of daratumumab in combination with bortezomib, lenalidomide, and dexamethasone (VRD) was then given. The patient achieved complete remission. She underwent allogeneic stem cell transplantation of an HLA-matched sibling donor. Post-transplant marrow assessment showed disease remission and absence of t(11;14) and 17p deletions. She was administered pamidronate and lenalidomide maintenance. She remained clinically well with a good performance status and no active graft-versus-host disease 18 months after transplant. CONCLUSIONS The success of our patient in achieving complete remission has highlighted the efficacy and safety of this novel therapy in the front-line management of PCL.
    Matched MeSH terms: Bortezomib
  2. Demirdöğen RE, Emen FM, Ocakoglu K, Murugan P, Sudesh K, Avşar G
    Int J Biol Macromol, 2018 Feb;107(Pt A):436-445.
    PMID: 28888547 DOI: 10.1016/j.ijbiomac.2017.09.011
    Carbon dioxide assisted particle formation combined with electrospraying using supercritical CO2 (scCO2) as an aid (Carbon Dioxide Assisted Nebulization-Electrodeposition, CAN-ED) was used to produce Bortezomib loaded poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) P(3HB-co-3HHx) nanoparticles for sustained release. The morphology and structure of the prepared nanoparticles were investigated by SEM, TEM and FT-IR spectroscopy. Average diameter of particles obtained was 155nm and the average core sizes of P(3HB-co-3HHx) nanoparticles were between 6 and 13nm. The drug loading capacity, drug release and stability of Bortezomib loaded P(3HB-co-3HHx) nanoparticles were analyzed. The maximum loading capacity was achieved at pH=6.0 in phosphate buffer (K2HPO4/KH2PO4). It was found that temperature did not affect the stability of Bortezomib loaded nanoparticles and it was good both at 37°C and 4°C. This study pointed out that CAN-ED is a green method to produce P(3HB-co-3HHx) nanoparticles for pH responsive targeting of Bortezomib especially to parts of the body where size exclusion is not crucial.
    Matched MeSH terms: Bortezomib/therapeutic use; Bortezomib/chemistry*
  3. Cheong CS, Tengku K Aziz TAH, Anuar NA, Bee PC, Chin EFM, Khairullah S, et al.
    Asian Pac J Cancer Prev, 2024 Feb 01;25(2):595-601.
    PMID: 38415546 DOI: 10.31557/APJCP.2024.25.2.595
    BACKGROUND: Multiple myeloma is the third most common hematologic malignancy in Malaysia. The introduction of novel agents over the past decades has improved patient outcome and survival substantially. However, these agents incur significant economic burden, thus leading to limited use in less developed countries. This study aims to report on the real-world treatment pattern and outcome of newly diagnosed multiple myeloma (NDMM) patients from a resource-constraint setting.

    METHODS: This is a retrospective study on NDMM patients diagnosed between 1 January 2008 and 31 December 2022 in a single academic center. Patients' demographic and treatment details were included for analysis of progression free survival (PFS) and overall survival (OS).

    RESULTS: One hundred and thirty-six NDMM patients with a median age of 64.0 years (ranged from 38 to 87 years old) were included. Bortezomib-containing regimens were the most commonly used induction agent, followed by thalidomide. Almost half of the patients (47.1%) achieved very good partial response (VGPR) or complete remission (CR), while 31.6% achieved partial response (PR). Bortezomib containing regimen was associated with significantly deeper and more rapid response, (p=0.001 and p=0.017, respectively) when compared to other agents. Only 22.8% of these patients proceeded to upfront autologous haematopoietic stem cell transplantation.  The median OS and PFS were 60.0 months and 25.0 months, respectively. Best initial response and upfront autologous stem cell transplantation (ASCT) were significantly associated with better PFS.

    CONCLUSION: Achieving at least a VGPR significantly associated with better outcome in NDMM patients. In a resource constrain country, we recommend incorporating bortezomib in the induction therapy followed with an upfront ASCT.

    Matched MeSH terms: Bortezomib/therapeutic use
  4. Tan D, Phipps C, Hwang WY, Tan SY, Yeap CH, Chan YH, et al.
    Lancet Haematol, 2015 Aug;2(8):e326-33.
    PMID: 26688485 DOI: 10.1016/S2352-3026(15)00097-6
    BACKGROUND: Patients with relapsed or refractory peripheral T-cell lymphoma have a poor prognosis after conventional chemotherapy. Approved novel agents have only modest single-agent activity in most subtypes of peripheral T-cell lymphoma. Panobinostat is a potent oral pan-deacetylase inhibitor. Findings of many preclinical studies have shown synergistic antilymphoma activity when panobinostat is combined with the proteasome inhibitor bortezomib. We aimed to study the effect of panobinostat and bortezomib in patients with relapsed or refractory peripheral T-cell lymphoma.

    METHODS: In this open-label, multicentre phase 2 trial, we recruited patients aged 21 years or older with relapsed or refractory peripheral T-cell lymphoma who had received at least one previous line of systemic therapy from five tertiary hospitals in Singapore, Malaysia, and South Korea. Patients received 20 mg oral panobinostat three times a week and 1·3 mg/m(2) intravenous bortezomib two times a week, both for 2 of 3 weeks for up to eight cycles. The primary endpoint was the proportion of patients who achieved an objective response in accordance with the International Working Group revised response criteria; analyses were by intention to treat. The study is completed and is registered with ClinicalTrials.gov, number NCT00901147.

    FINDINGS: Between Nov 9, 2009, and Nov 26, 2013, we enrolled 25 patients with various histological subtypes of peripheral T-cell lymphoma. Of 23 patients assessable for responses, ten (43%, 95% CI 23-63) patients had an objective response, of which five were complete responses. Serious adverse events were reported in ten (40%) of 25 patients. Common treatment-related grade 3-4 adverse events included thrombocytopenia (17 [68%]), neutropenia (ten [40%]), diarrhoea (five [20%]), and asthenia or fatigue (two [8%]). We recorded peripheral neuropathy of any grade in ten (40%) patients.

    INTERPRETATION: Combined proteasome and histone deacetylase inhibition is safe and feasible and shows encouraging activity for patients with peripheral T-cell lymphoma. Our findings validate those of preclinical studies showing synergism in the combination and represent a rational way forward in harnessing the full potential of novel agents in peripheral T-cell lymphoma.

    FUNDING: Novartis Pharmaceuticals, Janssen Pharmaceuticals, and Singhealth Foundation.

    Matched MeSH terms: Bortezomib/administration & dosage; Bortezomib/therapeutic use*
  5. Siddiqui R, Saleem S, Khan NA
    Exp Parasitol, 2016 Jun 18;168:16-24.
    PMID: 27327524 DOI: 10.1016/j.exppara.2016.06.006
    The treatment of Acanthamoeba infections remains problematic, suggesting that new targets and/or chemotherapeutic agents are needed. Bioassay-guided screening of drugs that are clinically-approved for non-communicable diseases against opportunistic eukaryotic pathogens is a viable strategy. With known targets and mode of action, such drugs can advance to clinical trials at a faster pace. Recently Bortezomib (proteasome inhibitor) has been approved by FDA in the treatment of multiple myeloma. As proteasomal pathways are well known regulators of a variety of eukaryotic cellular functions, the overall aim of the present study was to study the effects of peptidic and non-peptidic proteasome inhibitors on the biology and pathogenesis of Acanthamoeba castellanii of the T4 genotype, in vitro. Zymographic assays revealed that inhibition of proteasome had detrimental effects on the extracellular proteolytic activities of A. castellanii. Proteasome inhibition affected A. castellanii growth (using amoebistatic assays), but not viability of A. castellanii. Importantly, proteasome inhibitors affected encystation as determined by trophozoite transformation into the cyst form, as well as excystation, as determined by cyst transformation into the trophozoite form. The ability of proteasome inhibitor to block Acanthamoeba differentiation is significant, as it presents a major challenge in the successful treatment of Acanthamoeba infection. As these drugs are used clinically against non-communicable diseases, the findings reported here have the potential to be tested in a clinical setting against amoebic infections.
    Matched MeSH terms: Bortezomib
  6. Fatin Hanisah, F., Rona Asnida, N., Jemaima, C.H.
    Medicine & Health, 2018;13(2):217-222.
    MyJurnal
    Few cases of chalazia secondary to bortezomib are reported in literature. However, it is not a recognized ocular adverse effect. We hereby report a case of recurrent chalazia secondary to bortezomib. A 40-year-old male with light chain myeloma on ten weeks of chemotherapy with bortezomib was treated for left eye inflamed chalazion with bilateral meibominitis. Severe chalazia persisted despite treatment, which necessitated cessation of chemotherapy. The patient’s condition improved on oral doxycycline and chemotherapy was recommenced but his chalazia recurred, necessitating incision and curretage. His chalazia responded to oral azithromycin without further cessation of chemotherapy. Bortezomib’s association with chalazia has been characterized as a possible adverse drug reaction according to the World Health organization classification, and its recognization as an established adverse reaction to will allow earlier identification and appropriate co-management of the patient.

    Matched MeSH terms: Bortezomib
  7. Shrestha S, Poudel RS, Kc B, Poudel BK, Sapkota B, Sharma S, et al.
    PMID: 32266073 DOI: 10.1186/s40545-020-0203-0
    Objective: To assess the variation in price among different brands of anticancer medicines available in hospital pharmacies at Nepalese cancer hospitals.

    Methods: The price of different brands of the same anticancer medicines available in the hospital pharmacies of two cancer hospitals was assessed. Prices of different dosage forms such as a single tablet, capsule and vial were calculated. The difference in the maximum and minimum price of the same drug manufactured by different pharmaceutical industries was determined, and the percentage variation in price was calculated. The prices of medicines (brands) were also compared with the price determined by the government where available.

    Results: Price variation was assessed for 31 anticancer medicines belonging to six broad categories. Prices were found to vary maximally among the following medicines, each belonging to separate categories: among alkylating agents, the price of temozolomide 100 mg capsule varied 308%; among antimetabolite agents, the price of pemetrexed 500 mg injection varied 134%; among hormonal drugs, the price of letrozole 2.5 mg tablet varied 200%; among antibody class, the price of trastuzumab 440 mg injection varied 73%; among natural products, the price of irinotecan 100 mg injection varied 590%; and among miscellaneous agents, the price of bortezomib 2 mg injection varied 241%. There was a significant difference in the mean MRP of the alkylating agents with the antimetabolites (p-value 0.006) and the monoclonal antibody (p-value

    Matched MeSH terms: Bortezomib
  8. Kasinathan G
    BMJ Case Rep, 2020 Jul 23;13(7).
    PMID: 32709663 DOI: 10.1136/bcr-2020-235543
    Plasma cell leukaemia (PCL) is an aggressive haematological malignancy which is classified into primary (pPCL) and secondary PCL. A 39-year-old Indian man presented to the Department of Hematology with a 2-week history of fever and lethargy. Clinically, he was pale and febrile. Haemogram revealed bicytopenia with leucocytosis. The peripheral blood film portrayed rouleax formation with 45% of circulating plasma cells. Serum protein electrophoresis and immunofixation revealed IgG lambda paraproteinaemia of 48 g/L. Bone marrow aspirate, flow cytometry and trephine were consistent with IgG lambda pPCL. He was treated with six cycles of bortezomib, thalidomide and dexamethasone combination chemotherapy followed by high-dose melphalan conditioning and autologous stem cell transplant. Currently, he is in complete remission for the past 18 months and is on oral lenalidomide maintenance therapy. Prognosis is often dismal in pPCL with the median overall survival below 1 year if treatment is delayed.
    Matched MeSH terms: Bortezomib
  9. Abd-Aziz N, Stanbridge EJ, Shafee N
    Oncol Lett, 2015 Oct;10(4):2192-2196.
    PMID: 26622817
    Bortezomib is the first proteasomal inhibitor (PI) to be used therapeutically for treating relapse cases of multiple myeloma and mantle cell lymphoma. A proposed mechanism for its action is that it prevents the proteasomal degradation of proapoptotic proteins, leading to enhanced apoptosis. Although the α subunit of hypoxia-inducible factor (HIF)-1 is not degraded with bortezomib treatment, the heterodimeric HIF-1 fails to transactivate target genes. HIF-1 and HIF-2 are related hypoxia-inducible transcription factors that are important for the survival of hypoxic tumor cells. The majority of reports have focused on the effects of bortezomib on the transcriptional activities of HIF-1, but not HIF-2. The present study investigated the effects of bortezomib on HIF-2 activity in cancer cells with different levels of HIF-1α and HIF-2α subunits. HIF-α subunit levels were detected using specific antibodies, while HIF transcriptional activities were evaluated using immunodetection, reverse transcription-polymerase chain reaction and luciferase reporter assay. Bortezomib treatment was found to suppress the transcription and expression of CA9, a HIF-1-specific target gene; however, it had minimal effects on EPO and GLUT-1, which are target genes of both HIF-1 and HIF-2. These data suggest that bortezomib attenuates the transcriptional activity only of HIF-1, and not HIF-2. This novel finding on the lack of an inhibitory effect of bortezomib on HIF-2 transcriptional activity has implications for the improvement of design and treatment modalities of bortezomib and other PI drugs.
    Matched MeSH terms: Bortezomib
  10. Tay KC, Tan LT, Chan CK, Hong SL, Chan KG, Yap WH, et al.
    Front Pharmacol, 2019;10:820.
    PMID: 31402861 DOI: 10.3389/fphar.2019.00820
    Cancer, a complex yet common disease, is caused by uncontrolled cell division and abnormal cell growth due to a variety of gene mutations. Seeking effective treatments for cancer is a major research focus, as the incidence of cancer is on the rise and drug resistance to existing anti-cancer drugs is major concern. Natural products have the potential to yield unique molecules and combinations of substances that may be effective against cancer with relatively low toxicity/better side effect profile compared to standard anticancer therapy. Drug discovery work with natural products has demonstrated that natural compounds display a wide range of biological activities correlating to anticancer effects. In this review, we discuss formononetin (C16H12O4), which originates mainly from red clovers and the Chinese herb Astragalus membranaceus. The compound comes from a class of 7-hydroisoflavones with a substitution of methoxy group at position 4. Formononetin elicits antitumorigenic properties in vitro and in vivo by modulating numerous signaling pathways to induce cell apoptosis (by intrinsic pathway involving Bax, Bcl-2, and caspase-3 proteins) and cell cycle arrest (by regulating mediators like cyclin A, cyclin B1, and cyclin D1), suppress cell proliferation [by signal transducer and activator of transcription (STAT) activation, phosphatidylinositol 3-kinase/protein kinase-B (PI3K/AKT), and mitogen-activated protein kinase (MAPK) signaling pathway], and inhibit cell invasion [by regulating growth factors vascular endothelial growth factor (VEGF) and Fibroblast growth factor 2 (FGF2), and matrix metalloproteinase (MMP)-2 and MMP-9 proteins]. Co-treatment with other chemotherapy drugs such as bortezomib, LY2940002, U0126, sunitinib, epirubicin, doxorubicin, temozolomide, and metformin enhances the anticancer potential of both formononetin and the respective drugs through synergistic effect. Compiling the evidence thus far highlights the potential of formononetin to be a promising candidate for chemoprevention and chemotherapy.
    Matched MeSH terms: Bortezomib
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