scholarly journals Post-chemotherapy maintenance treatment by nicotinamide riboside, a poly ADP ribose polymerase 1 inhibitor, in BRCA mutated advanced ovarian cancer – A perspective

2021 ◽  
Vol 0 ◽  
pp. 1-4
Author(s):  
Mukul Arvind Gharote ◽  
Amruta Ashok Deshpande
Keyword(s):  
Maintenance Treatment ◽  
Indian Subcontinent ◽  
Advanced Ovarian Cancer ◽  
Current Evidence ◽  
High Dose ◽  
Maintenance Chemotherapy ◽  
Vitamin B3 ◽  
Nicotinamide Riboside ◽  
Toxic Potential ◽  
Parp 1

Poly ADP ribose polymerase 1 (PARP-1) inhibitors are approved for post-chemotherapy maintenance in BRCA mutated ovarian carcinoma. Various PARP-1 inhibitors such as olaparib, rucaparib, niraparib, and veliparib are approved for this indication. These PARP-1 inhibitors are costly as well as having toxic potential, anemia, and neutropenia is the major side effects. Most of the middle-aged women in Indian subcontinent are anemic and prescription of PARP-1 inhibitors is tricky in such conditions, besides their cost is at times unaffordable as maintenance chemotherapy. Hence, we need an affordable yet lesser toxic PARP-1 inhibitor to solve this problem. Nicotinamide, a vitamin B3 amide can be re-purposed as PARP-1 inhibitor. Nicotinamide, albeit at a higher dose, can be efficacious as well as economical in its use as maintenance chemotherapy. It has toxic potential but the toxicity is both rare and manageable. We need a clinical trial for this purpose. Following perspective is on the current evidence on high dose nicotinamide and it is re-purposing as PARP-1 inhibitor.

scholarly journals Equilibrative Nucleoside Transporters Mediate the Import of Nicotinamide Riboside and Nicotinic Acid Riboside into Human Cells

2021 ◽  
Vol 22 (3) ◽  
pp. 1391
Author(s):  
Andrey Kropotov ◽  
Veronika Kulikova ◽  
Kirill Nerinovski ◽  
Alexander Yakimov ◽  
Maria Svetlova ◽  
...  
Keyword(s):  
Nicotinic Acid ◽  
Mammalian Cells ◽  
Experimental Models ◽  
The Body ◽  
Nucleoside Transporters ◽  
Hek293 Cells ◽  
Nucleoside Transporter ◽  
Vitamin B3 ◽  
Animal Cells ◽  
Nicotinamide Riboside

Nicotinamide riboside (NR), a new form of vitamin B3, is an effective precursor of nicotinamide adenine dinucleotide (NAD+) in human and animal cells. The introduction of NR into the body effectively increases the level of intracellular NAD+ and thereby restores physiological functions that are weakened or lost in experimental models of aging and various pathologies. Despite the active use of NR in applied biomedicine, the mechanism of its transport into mammalian cells is currently not understood. In this study, we used overexpression of proteins in HEK293 cells, and metabolite detection by NMR, to show that extracellular NR can be imported into cells by members of the equilibrative nucleoside transporter (ENT) family ENT1, ENT2, and ENT4. After being imported into cells, NR is readily metabolized resulting in Nam generation. Moreover, the same ENT-dependent mechanism can be used to import the deamidated form of NR, nicotinic acid riboside (NAR). However, NAR uptake into HEK293 cells required the stimulation of its active utilization in the cytosol such as phosphorylation by NR kinase. On the other hand, we did not detect any NR uptake mediated by the concentrative nucleoside transporters (CNT) CNT1, CNT2, or CNT3, while overexpression of CNT3, but not CNT1 or CNT2, moderately stimulated NAR utilization by HEK293 cells.

Short-term corticosteroid therapy in childhood asthma

1976 ◽  
Vol 14 (8) ◽  
pp. 31-32
Keyword(s):  
Sodium Cromoglycate ◽  
Corticosteroid Therapy ◽  
Childhood Asthma ◽  
Maintenance Treatment ◽  
High Dose ◽  
Severe Exacerbation ◽  
Short Term ◽  
At Home

Attacks of asthma in most children are relatively mild, but in a few they are severe and potentially fatal.1 The severity of attacks can be reduced by β-adrenoceptor stimulants, theophylline compounds and sodium cromoglycate, but when these are not effective it may be necessary to give a corticosteroid continuously. For those children who develop a severe exacerbation despite maintenance treatment, or those who get infrequent but often severe attacks that do not respond to bronchodilators, a short high-dose course of a corticosteroid can be given, and many practitioners choose to give this to their patients at home.2 However since no trials of such treatment have been performed the benefit remains unproven.

Association study of genetic polymorphisms in GABRD with treatment response and dose in methadone maintenance treatment

2021 ◽  
Author(s):  
Xiaohu Xie ◽  
Jun Gu ◽  
Dingding Zhuang ◽  
Xiaoyu Chen ◽  
Yun Zhou ◽  
...  
Keyword(s):  
Treatment Response ◽  
Methadone Maintenance Treatment ◽  
Maintenance Treatment ◽  
Methadone Maintenance ◽  
Methadone Treatment ◽  
Heroin Addiction ◽  
High Dose ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Delta Subunit

Aim: This study determined if gene variants in the GABA receptor delta subunit ( GABRD) are associated with treatment response and dose in methadone maintenance treatment (MMT) for heroin addiction. Materials & methods: A total of 286 MMT patients were recruited and divided into response and nonresponse groups based on retention time in therapy. A total of 177 responders were classified into low dose and high dose subgroups according to the stabilized methadone dose. Four (single nucleotide polymorphisms) SNPs (rs13303344, rs4481796, rs2376805 and rs2229110) in GABRD were genotyped using the TaqMan SNP assay. Logistic regression was used to assess the genetic effects of the SNPs in MMT. Results: No significant associations were observed between the SNPs and treatment response or dose, except the frequency of haplotype ACGC at the four SNPs significantly differed between responders and nonresponders. Conclusion: The results indicated that GABRD variants may play a small role in modulating methadone treatment response.

Maximal Cytoreductive Surgery and High Dose Cisplatin Chemotherapy for Advanced Ovarian Cancer

2010 ◽  
Vol 19 (4) ◽  
pp. 375-381 ◽  
Author(s):  
Kazunori Ochiai ◽  
Satoshi Takakura ◽  
Seiji Isonishi ◽  
Hiroshi Sasaki ◽  
Yoshiteru Terashima
Keyword(s):  
Ovarian Cancer ◽  
Cytoreductive Surgery ◽  
Advanced Ovarian Cancer ◽  
High Dose

Cyclophosphamide (CTX) and high-dose 4-Epidoxorubicin (EPI) in advanced ovarian cancer (OC) treatment

1994 ◽  
pp. 469-472
Author(s):  
G. Cartei ◽  
M. Signor ◽  
E. Vigevani ◽  
M. Giovannoni ◽  
A. Sibau ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Advanced Ovarian Cancer ◽  
High Dose

scholarly journals High-Dose Chemotherapy with Bendamustin and Melphalan Improves the Rate of Complete Remission in Myeloma Patients in First Remission Compared to Standard Melphalan Alone

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 39-40
Author(s):  
Sarah Farag ◽  
Ulrike Bacher ◽  
Myriam Legros ◽  
Daniel Betticher ◽  
Jean-Marc Lüthi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Flow Cytometry ◽  
Complete Remission ◽  
Median Time ◽  
Maintenance Treatment ◽  
Induction Treatment ◽  
High Dose ◽  
First Line ◽  
Term Survival ◽  
Pulmonary Failure

Introduction: Consolidation of first-line induction treatment in myeloma (MM) patients (pts) with 200 mg/m2 melphalan chemotherapy (HDCT) and autologous stem cell transplantation (ASCT) was established as standard of care three decades ago. However, definite cure in myeloma patients remains exceptional due to residual disease escaping intensive treatment, and almost all patients will ultimately relapse at earlier or later time points following ASCT. Thus, improving efficacy of HDCT in MM remains an unresolved issue. Methods: We performed a phase-II randomized trial comparing standard 200 mg/m2 Melphalan (Mel) HDCT to experimental HDCT treatment with 200 mg/m2 bendamustine, a bifunctional alkylating agent, given at days -4 and -3, combined with 200 mg/m2 melphalan split on days -2 and -1 at 100 mg/m2 (BenMel) before ASCT in MM pts. Patients had up to four cycles of first-line induction treatment with bortezomib, lenalidomide and dexamethasone. After ASCT, pts received lenalidomide maintenance treatment for two years. The primary endpoint was to show a 15% improvement of the rate of complete remission (sCR+CR) after HDCT with BenMel compared to Mel alone. MRD assessment from the bone marrow was performed by multiparameter flow cytometry after hematological engraftment following HDCT/ASCT. MRD negativity was defined as clonal plasma cells below 10(-5). Results: We randomized 120 myeloma pts (60 patients in each arm), with high-risk genetic abnormalities present in 21.3% of the patients. The median age was 63 years (range 35-74). The sCR/CR rate after ASCT before initiation of lenalidomide maintenance treatment was better in the BenMel arm compared to Mel alone (70.0% vs 51.7%; p=.039). The post-ASCT remission rates in detail were sCR 40.0% vs 31.7% (p=.341); CR 30.0% vs 20.0% (p=.205); VGPR 16.7% vs 33.3% (p=.035); and PR 13.3% vs 15.0% (p=.793). MRD negativity assessed in the bone marrow by flow cytometry was observed in 26 (45.6%) of the BenMel treated pts compared to 22 (37.9%) of the Mel pts. Median time until neutrophil engraftment was 11 days after BenMel vs 12 days after Mel (p=.096), and median time until platelet engraftment was 13 days in both arms (p=0.367); all pts had full engraftment of both cell lineages. Prolonged hospitalization duration was seen in BenMel pts (median 19 vs 18 days; p=.006) due to the longer BenMel treatment administration. Fully reversible acute renal insufficiency occurred in three (5%) BenMel pts compared to none of the Mel pts (p=.250). No treatment-related mortality was seen in both groups. ICU admissions were necessary in 3 pts (5%) in the BenMel group (ARDS, septic shock, pulmonary failure), and 2 Mel treated pts (3.3%; due to pulmonary failure and decompensated cardiomyopathy). The PFS rates at 12 months were 95% in BenMel pts and 91% in Mel treated pts (p=.551). OS at 12 months was 96% for both groups (p=.262), and median PFS and OS were not reached in both groups. Conclusions: Our data confirm that high-dose bendamustine combined with melphalan HDCT before ASCT in MM patients is safe and well tolerated. In particular, bendamustine-associated renal toxicity was manageable and reversible in all patients, and hematopoietic engraftment was comparable to standard melphalan HDCT. HDCT with BenMel improves the sCR/CR rate compared to standard melphalan alone. Thus, BenMel HDCT before ASCT warrants further investigation aiming to improve the long-term survival rates of MM patients, eventually combined with new maintenance strategies in the post-transplant period. Figure 1 Disclosures No relevant conflicts of interest to declare.

Letrozole in the management of advanced ovarian cancer: an old drug as a new targeted therapy

2020 ◽  
Vol 30 (7) ◽  
pp. 1058-1064
Author(s):  
Claudia Marchetti ◽  
Francesca De Felice ◽  
Raffaella Ergasti ◽  
Giovanni Scambia ◽  
Anna Fagotti
Keyword(s):  
Ovarian Cancer ◽  
Maintenance Treatment ◽  
Advanced Ovarian Cancer ◽  
Standard Of Care ◽  
Low Grade ◽  
Toxicity Profile ◽  
Biologically Relevant ◽  
Cancer Management ◽  
Free Interval ◽  
Optimal Setting

At present, there is no standard of care on the use of letrozole in ovarian cancer management. We performed a systematic review of the available literature addressing this issue. Data demonstrated a role for letrozole in ovarian cancer, in both the primary and recurrent setting. Letrozole, which has a favorable toxicity profile, seems to assure a prolonged recurrence-free interval, particularly when used as maintenance treatment, in low grade serous ovarian cancer; in recurrent cases it had also led to prolonged disease control. However, the optimal setting and biologically relevant patient population needs to be defined in larger trials.

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