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  1. Alfaleh MA, Fahmy O, Al-Rabia MW, Abourehab MAS, Ahmed OAA, Fahmy UA, et al.
    Sci Rep, 2022 Nov 14;12(1):19446.
    PMID: 36376469 DOI: 10.1038/s41598-022-24151-3
    As a hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, Fluvastatin (FLV) is used for reducing low-density lipoprotein (LDL) cholesterol as well as to prevent cardiovascular problems. FLV showed cell line cytotoxicity and antitumor effect. Melittin (MEL) exhibits antineoplastic activity and is known to be promising as a therapeutic option for cancer patients. The aim of this work was to investigate the combination of FLV with MEL loaded hybrid formula of phospholipid (PL) with alpha lipoic acid (ALA) nanoparticles to maximize anticancer tendencies. This study examines the optimization of the prepared formulation in order to minimize nanoparticles size and maximize zeta potential to potentiate cytotoxic potentialities in colon cancer cells (Caco2), cell viability, cell cycle analysis and annexin V were tested. In addition to biological markers as P53, Bax, bcl2 and Caspase 3 evaluation The combination involving FLV PL ALA MEL showed enhanced cytotoxic potentiality (IC50 = 9.242 ± 0.35 µg/mL), about twofold lower, compared to the raw FLV (IC50 = 21.74 ± 0.82 µg/mL). According to studies analyzing cell cycle, optimized FLV PL ALA MEL was found to inhibit Caco2 colon cancer cells more significantly than other therapeutic treatments, wherein a higher number of cells were found to accumulate over G2/M and pre-G1 phases, whereas G0/G1/S phases witnessed the accumulation of a lower number of cells. The optimized formulation may pave the way for a novel and more efficacious treatment for colon cancer.
    Matched MeSH terms: Indoles/therapeutic use
  2. Navookarasu NT, Rahman AR, Abdullah I
    Int J Clin Pract, 1999 Jan-Feb;53(1):25-30.
    PMID: 10344062
    Despite their proven value in reducing morbidity and mortality in different grades of heart failure, angiotensin converting enzyme (ACE) inhibitors continue to be underused. One reason for this is clinicians' apprehension of first-dose hypotension. We conducted a double-blind, randomised, placebo-controlled parallel group study to investigate the effect of various ACE inhibitors on first-dose hypotension. Eighty unselected patients were randomised into five treatment groups: placebo, captopril 6.25 mg, enalapril 2.5 mg, perindopril 2 mg and lisinopril 2.5 mg. Blood pressure was measured at baseline, half hourly for two hours and hourly for three hours after drug treatment. The maximum drops in mean arterial pressure (in mmHg +/- SD) were placebo 5.89 +/- 2.65, perindopril 5.29 +/- 2.49, enalapril 13.28 +/- 3.31, lisinopril 15.04 +/- 5.74 and captopril 16.76 +/- 5.74 (all p < 0.05 vs placebo except for perindopril). Perindopril, unlike the other ACE inhibitors studied, did not produce first-dose hypotension following its initiation in patients with congestive heart failure.
    Matched MeSH terms: Indoles/therapeutic use
  3. Chia YC, Lim SH, Wang SJ, Cheong YM, Denaro J, Hettiarachchi J
    Headache, 2003 Oct;43(9):984-90.
    PMID: 14511275
    BACKGROUND/OBJECTIVE: Nonsteroidal anti-inflammatory drugs continue to be one of the most widely used therapies for migraine, but their efficacy in treating moderate to severe migraine headache has not been well documented. In contrast, the efficacy of triptans in this group of patients is well documented, although no systematic research is available that evaluates the effectiveness of switching to a triptan in patients who respond poorly to nonsteroidal anti-inflammatory drugs.

    METHODS: One hundred thirteen patients who met International Headache Society criteria for migraine and who did not experience satisfactory response to nonsteroidal anti-inflammatory drugs, received open-label treatment with a 40-mg dose of eletriptan for one migraine attack. Efficacy assessments were made at 1, 2, 4, and 24 hours postdose and consisted of headache and pain-free response rates, absence of associated symptoms, and functional response. Global ratings of treatment effectiveness and preference were obtained at 24 hours.

    RESULTS: The pain-free response rate at 2 hours postdose was 25% and at 4 hours postdose, 55%; the headache response rate at 2 hours was 66% and at 4 hours, 87%. At 2 hours postdose, relief of baseline associated symptoms was achieved by 41% of patients with nausea compared to 82% of patients at 4 hours; for patients with phonophobia, 67% were relieved at 2 hours and 93% at 4 hours, and for patients with photophobia, 70% were relieved at 2 hours and 91% at 4 hours. Functional response was achieved by 70% of patients by 2 hours postdose. The high level of acute response was maintained over 24 hours, with only 24% of patients experiencing a headache recurrence and only 10% using rescue medication. At 24 hours postdose, 74% of patients rated eletriptan as preferable to any previous treatment for migraine. The most frequent reasons cited for this treatment preference were faster headache improvement (83%) and functional response (78%). Overall, eletriptan was well tolerated; most adverse events were transient and mild to moderate in severity. No serious adverse events were reported.

    CONCLUSION: Results of this open-label trial found the 40-mg dose of eletriptan to have a high degree of efficacy and tolerability among patients who responded poorly to nonsteroidal anti-inflammatory drugs.

    Matched MeSH terms: Indoles/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: Indoles/therapeutic use*
  5. Lim NK, Aik OT, Meng LL, Htun TH, Razack AH
    J Coll Physicians Surg Pak, 2014 Mar;24 Suppl 1:S68-70.
    PMID: 24718014 DOI: 03.2014/JCPSP.S68S70
    Superior vena caval syndrome (SVCS) is a debilitating condition attributed to malignancy in more than 70% of cases. However, solitary head and neck metastases arising from renal cell carcinomas without evidence of disease elsewhere are rare. We report a case of renal cell carcinoma presenting as a rapidly growing right cervical lymph node with compression on the subclavian vein causing superior vena caval syndrome (SVCS). There was pulmonary embolism as well. Biopsy of the neck mass confirmed metastatic clear cell carcinoma with primary found in the (L) kidney. The patient had partial response to focussed radiotherapy to neck mass and Sunitinib (tyrosine kinase inhibitor) before succumbing to the disease.
    Matched MeSH terms: Indoles/therapeutic use
  6. Nazir M, Abbasi MA, Aziz-Ur-Rehman -, Siddiqui SZ, Ali Shah SA, Shahid M, et al.
    Pak J Pharm Sci, 2019 Nov;32(6):2585-2597.
    PMID: 31969290
    In the study presented here, the nucleophilic substitution reaction of 5-[3-(1H-indol-3-yl)propyl]-1,3,4-oxadiazol-2-ylhydrosulfide was carried out with different alkyl/aralkyl halides (5a-r) to form its different S-substituted derivatives (6a-r), as depicted in scheme 1. The structural confirmation of all the synthesized compounds was done by IR, 1H-NMR, 13C-NMR and CHN analysis data. Bacterial biofilm inhibitory activity of all the synthesized compounds was carried out against Bacillus subtilis and Escherichia coli. The anticancer activity of these molecules was ascertained using anti-proliferation (SRB) assay on HCT 116 Colon Cancer Cell lines while the cytotoxicity of these molecules was profiled for their haemolytic potential. From this investigation it was rational that most of the compounds exhibited suitable antibacterial and anticancer potential along with a temperate cytotoxicity.
    Matched MeSH terms: Indoles/therapeutic use
  7. Gobe GC, Ng KL, Small DM, Vesey DA, Johnson DW, Samaratunga H, et al.
    Biochem Biophys Res Commun, 2016 Apr 22;473(1):47-53.
    PMID: 26995091 DOI: 10.1016/j.bbrc.2016.03.048
    Apoptosis repressor with caspase recruitment domain (ARC), an endogenous inhibitor of apoptosis, is upregulated in a number of human cancers, thereby conferring drug resistance and giving a rationale for the inhibition of ARC to overcome drug resistance. Our hypothesis was that ARC would be similarly upregulated and targetable for therapy in renal cell carcinoma (RCC). Expression of ARC was assessed in 85 human RCC samples and paired non-neoplastic kidney by qPCR and immunohistochemistry, as well as in four RCC cell lines by qPCR, Western immunoblot and confocal microscopy. Contrary to expectations, ARC was significantly decreased in the majority of clear cell RCC and in three (ACHN, Caki-1 and 786-0) of the four RCC cell lines compared with the HK-2 non-cancerous human proximal tubular epithelial cell line. Inhibition of ARC with shRNA in the RCC cell line (SN12K1) that had shown increased ARC expression conferred resistance to Sunitinib, and upregulated interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF). We therefore propose that decreased ARC, particularly in clear cell RCC, confers resistance to targeted therapy through restoration of tyrosine kinase-independent alternate angiogenesis pathways. Although the results are contrary to expectations from other cancer studies, they were confirmed here with multiple analytical methods. We believe the highly heterogeneous nature of cancers like RCC predicate that expression patterns of molecules must be interpreted in relation to respective matched non-neoplastic regions. In the current study, this procedure indicated that ARC is decreased in RCC.
    Matched MeSH terms: Indoles/therapeutic use*
  8. Bonsu KO, Owusu IK, Buabeng KO, Reidpath DD, Kadirvelu A
    J Am Heart Assoc, 2017 Apr 01;6(4).
    PMID: 28365564 DOI: 10.1161/JAHA.116.004706
    BACKGROUND: Randomized control trials of statins have not demonstrated significant benefits in outcomes of heart failure (HF). However, randomized control trials may not always be generalizable. The aim was to determine whether statin and statin type-lipophilic or -hydrophilic improve long-term outcomes in Africans with HF.

    METHODS AND RESULTS: This was a retrospective longitudinal study of HF patients aged ≥18 years hospitalized at a tertiary healthcare center between January 1, 2009 and December 31, 2013 in Ghana. Patients were eligible if they were discharged from first admission for HF (index admission) and followed up to time of all-cause, cardiovascular, and HF mortality or end of study. Multivariable time-dependent Cox model and inverse-probability-of-treatment weighting of marginal structural model were used to estimate associations between statin treatment and outcomes. Adjusted hazard ratios were also estimated for lipophilic and hydrophilic statin compared with no statin use. The study included 1488 patients (mean age 60.3±14.2 years) with 9306 person-years of observation. Using the time-dependent Cox model, the 5-year adjusted hazard ratios with 95% CI for statin treatment on all-cause, cardiovascular, and HF mortality were 0.68 (0.55-0.83), 0.67 (0.54-0.82), and 0.63 (0.51-0.79), respectively. Use of inverse-probability-of-treatment weighting resulted in estimates of 0.79 (0.65-0.96), 0.77 (0.63-0.96), and 0.77 (0.61-0.95) for statin treatment on all-cause, cardiovascular, and HF mortality, respectively, compared with no statin use.

    CONCLUSIONS: Among Africans with HF, statin treatment was associated with significant reduction in mortality.

    Matched MeSH terms: Indoles/therapeutic use
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