I. Bernard Weinstein's research while affiliated with Columbia University and other places

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Publications (650)


Cell Culture Studies on the Biologic Effects of Tumor Promoters
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March 2019

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I.Bernard Weinstein

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Increased anxiety-related behaviour in Hint1 knockout mice

February 2011

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62 Reads

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59 Citations

Behavioural Brain Research

Several reports have implicated a role for the histidine triad nucleotide-binding protein-1 (Hint1) in psychiatric disorders. We have studied the emotional behaviour of male Hint1 knockout (Hint1 KO) mice in a battery of tests and performed biochemical analyses on brain tissue. The behavioural analysis revealed that Hint1 KO mice exhibit an increased emotionality phenotype compared to wildtype (WT) mice, while no significant differences in locomotion or general exploratory activity were noted. In the elevated plus-maze (EPM) test, the Hint1 KO animals entered the open arms of the apparatus less often than WT littermates. Similarly, in the dark-light box test, Hint1 KO mice spent less time in the lit compartment and the number of entries were reduced, which further confirmed an increased anxiety-related behaviour. Moreover, the Hint1 KO animals showed significantly more struggling and less floating behaviour in the forced swim test (FST), indicating an increased emotional arousal in aversive situations. Hint1 is known as a protein kinase C (PKC) interacting protein. Western blot analysis showed that PKCγ expression was elevated in Hint1 KO compared to WT mice. Interestingly, PKCγ mRNA levels of the two groups did not show a significant difference, implying a post-transcriptional PKCγ regulation. In addition, PKC enzymatic activity was increased in Hint1 KO compared to WT mice. In summary, our results indicate a role for Hint1 and PKCγ in modulating anxiety-related and stress-coping behaviour in mice.





Citations (78)


... Research on the CNS function of HINT1 has revealed that the protein interacts specifically with the C-terminus of the µ-opioid receptor. The absence of HINT1 leads to decreased receptor desensitization and the inhibition of PKC-mediated µ-opioid receptor phosphorylation [17]. This can result in enhanced basal and morphine-induced antinociception, improved morphine tolerance, and increased sensitivity to the effects of amphetamine and apomorphine. ...

Reference:

The HINT1 Gene rs2526303 Polymorphism and Its Association with Personality Traits in Cigarette Smokers
Role of mPKCI, a Novel μ-Opioid Receptor Interactive Protein, in Receptor Desensitization, Phosphorylation, and Morphine-Induced Analgesia
  • Citing Article
  • November 2004

Molecular Pharmacology

... We should emphasize that in the present study, we used high concentrations of Exisulind (300-600 Amol/L), but the plasma levels in humans is 20 to 50 Amol/L (27). However, in vivo Exisulind undergoes enterohepatic recirculation and with chronic exposure, the tissue levels in the intestine and intestinal tumors may be higher. ...

Select Cyclic Nucleotide Phosphodiesterase Inhibitors in Colon Tumor Chemoprevention and Chemotherapy
  • Citing Chapter
  • January 2004

... 8 Acyclic retinoid (ACR; also known as all-trans-3,7,11,15-tetramethyl-2,4,6,10,14-hexadecapentaenoic acid, peretinoin, and NIK-333) is an orally administrated vitamin A derivative that binds to cellular retinoic acidbinding protein with the same affinity as all-trans retinoic acid, 9 and selectively induces RAR-β-dependent signaling. 10 Animal studies have shown that ACR exhibits substantial chemopreventive activity against chemically induced or metabolic syndrome-associated HCC. 11,12 In addition to the genomic regulation of retinoid signaling pathways, non-genomic effects of ACR, such as retinoid X receptor (RXR)-α hyper-phosphorylation inhibition 13 and aberrant lipid desaturation 14,15 may also be responsible for its anti-HCC activity. ...

Acyclic retinoid activates retinoic acid receptor beta and induces transcriptional activation of p21(CIP1) in HepG2 human hepatoma cells
  • Citing Article
  • March 2004

Molecular Cancer Therapeutics

... It has been reported that the main active components of tea polyphenols are flavanols, commonly known as tea catechins, which include (À)-epigallocatechin-3-gallate (EGCG), (À)-epicate- chin-3-gallate (ECG), (À)-epigallocatechin (EGC) and (À)-epicatechin (EC) (Camouse et al., 2005; Fu et al., 2008; Mukhtar and Ahmad, 2000; Yang and Landau, 2000). Although researchers have found that the main active component of tea, EGCG, may inhibit the activity and induce apoptosis of cancer cells (Jagtap et al., 2009; Lang et al., 2009; Liu et al., 2008; Masuda et al., 2001; Tan and Spivack, 2009; Weinstein et al., 2003), it is unclear if daily intake of green tea would interfere with the pharmacokinetics and pharmacodynamics of a chemotherapy regimen used by cancer patients. Therefore, it is important to evaluate the effects of green tea at daily dose on the bioavailability and the net therapeutic potential of co-administered chemical drugs. ...

EGCG targets the epidermal growth factor (EGF) and HER-2 receptors in human cancer cells.
  • Citing Conference Paper
  • September 2003

ACS National Meeting Book of Abstracts

... Importantly, due to the lack of characterization and/or standardization for many preparations of black cohosh, the results and conclusions drawn from this study are limited to the specific water/ethanol extract of black cohosh used and the dose regimen described. The extraction method has been shown to play a critical role in the chemical profile and biological activity of black cohosh extract (Jiang et al., 2008). While our study utilized a water/ethanol extract, many of the previous studies in the OVX rat model used an isopropanolic extract. ...

Extraction Methods Play a Critical Role in Chemical Profile and Biological Activities of Black Cohosh
Natural Product Communications

Natural Product Communications

... In both DSM-V and DSM-V-TR [14], it has been acknowledged that nicotine withdrawal can occur in adolescent smokers even prior to daily tobacco use, and that significant symptoms of nicotine withdrawal can occur in nondaily smokers. In the clinic [7,15], people frequently report symptoms of withdrawal after their first cigarette, and most smokers report the experience of withdrawal symptoms even before progressing to daily smoking. These findings collectively indicate that nicotine can induce acute dependence in animals. ...

Encyclopedia of Cancer
  • Citing Chapter
  • January 2011

... The oncogenes KRAS , BRAF , NRAS and PIK3CA were among the top ranking context essential genes ( Figure 1C). Cells with mutations in these genes are well known to become selectively dependent on them through oncogene addiction indicating that we correctly identified context-dependent essentiality (Weinstein and Joe, 2008) . Gene set enrichment analysis (Sergushichev, 2016) further revealed that TFs (Gene Ontology Consortium, 2015) were indeed overrepresented among the most context-dependent essential genes (NES = 1.45, ...

Oncogene addiction versus oncogene amnesia: Perhaps more than just a bad habit? - Response
  • Citing Article
  • May 2008

Cancer Research

... Furthermore, in the same manner as seen by Nishimura and coauthors (2006) in human hepatoma cells, the migration of Res286 was significantly reduced. Additionally, others have shown that this drug reduces the expression of genes that induce angiogenesis (VEGF) [50], invasion (MMP-2, MMP-9) [3,17], and Table 1 Median dose effect analysis was also employed to characterize the interactions between DHMEQ and TMZ. For concomitant treatment, different doses of DHMEQ were combined with 250 μM TMZ and treated for 48 h. ...

Effects of a novel NF‐κB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), on growth, apoptosis, gene expression, and chemosensitivity in head and neck squamous cell carcinoma cell lines
  • Citing Article
  • February 2006

Head & Neck

... Furthermore, S. aqueum methanolic leaf extract was found to have high DPPH radical scavenging activity, as S. aqueum fruits have an IC 50 of 0.006 mg/mL (Sobeh et al., 2018). Syzygium samarangense, which is known as wax apple, had reordered antioxidant activity where the IC 50 of methanolic pulp and seed power in scavenging DPPH radicals were 0.072 mg/mL and 0.078 mg/mL, respectively (Simirgiotis et al., 2008). Similarly, the DPPH radical scavenging activity of S. samarangense leaf extracts was reported to have an IC 50 of 0.094 mg/ mL, 0.074 mg/mL, and 0.929 mg/mL using n-Hexane, athel acetate, and methanol as solvents, respectively (Budiono et al., 2019). ...

Cytotoxic chalcones and antioxidants from the fruits of Syzygium samarangense (Wax Jambu)
  • Citing Article
  • March 2008

Food Chemistry

... Studies by Liu et al. (2021) [18] have shown that the HINT1 protein is involved in various stages of addiction and may attenuate morphine addiction behaviour and withdrawal symptoms. In addition, studies using HINT1 knockout mice suggest that HINT1 may play a role in antidepressant and anxiety-like behaviours [19,20]. A study by Jackson et al. (2011) [21] found that genetic variation in the HINT1 gene is protective against nicotine dependence (ND), and the levels of the HINT1 protein in the nucleus accumbens are changed after prolonged exposure to nicotine, suggesting a role for HINT1 in nicotine-mediated responses. ...

Increased anxiety-related behaviour in Hint1 knockout mice
  • Citing Article
  • February 2011

Behavioural Brain Research