Peteris Alberts

Peteris Alberts
IVC · R&D

PhD

About

76
Publications
7,330
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2,091
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September 1976 - July 1982
Karolinska Institutet
Position
  • Researcher

Publications

Publications (76)
Article
Melanoma is a global problem due to the rising numbers of skin melanoma cases. Current treatment guidelines for patients with stage IIA melanoma recommend only observation after surgery. In this report, the authors describe a patient with stage IIA skin melanoma treated with surgery and Rigvir virotherapy. Two years after the patient discovered a b...
Article
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The oncolytic ECHO-7 virus Rigvir was registered in Latvia in 2004 and later in Georgia, Armenia and Uzbekistan. No severe adverse events have been observed. During drug development good laboratory practice (GLP) pre-clinical toxicology studies are generally required by regulatory agencies. Since such studies had previously not been performed the a...
Article
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Primary malignant melanoma of the uterine cervix is a rare disease with poor prognosis and high recurrence rate. We used Rigvir® as adjuvant therapy for a stage IVA patient. Tolerability, overall and progression‐free survival are good.
Article
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I would like to make the following corrections to the publication by McCarthy et al [...]
Article
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Melanoma is an aggressive skin cancer form with a grave prognosis. Current results suggest that oncolytic virus treatment of melanoma has a high therapeutic potential. ECHO-7 (Rigvir) is the first oncolytic virus registered in Latvia. A female patient was diagnosed with stage IIIB melanoma in December 2012, over 9.4 years ago. After the first excis...
Article
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Adrenal gland melanoma is an extremely rare diagnosis with less than 20 cases reported. The criteria for diagnosing adrenal gland melanoma include involvement of only one adrenal gland, presence of melanin pigment in the histological examination of the tumor tissue, no primary melanoma tumor in any other organ, and no history of resection of pigmen...
Article
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Objective: Uveal melanoma is a rare intraocular malignancy. Half of the patients diagnosed will develop metastases within 10 to 30 years, most commonly in the liver. Although there has been a significant development in the treatment of melanoma, no effective treatment to prevent or treat metastases of uveal melanoma is available. Oncolytic viruses...
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Purpose: To describe a case of choroidal melanoma treated with Rigvir® virotherapy in an adjuvant setting. Observations: A female patient born in 1956 presented with a small choroidal melanoma in October 2007. 34 months after transpupillary thermotherapy the state of her eye worsened until tumor growth was visualized. Despite photodynamic therap...
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Full-text available
Rationale: Of all the parts of the larynx, the glottis has the highest frequency of cancer. With disease progression, the vocal cord movement is affected and for advanced stages its anatomical and functional preservation is rarely achievable, if at all. Patient concerns: Here we describe a 72-year-old patient who presented with hoarseness for a...
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A 35‐year‐old male patient was diagnosed with stage IIC skin melanoma that rapidly progressed after surgery. Treatment was continued with radiotherapy, which did not stop further spread of disease and the patient was put on a combination of nivolumab and Rigvir. Subsequently, the progression has slowed. A 35‐year‐old male patient was diagnosed with...
Article
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Patient: Male, 59 Final Diagnosis: Chromophobe renal cell carcinoma, stage IV Symptoms: Discomfort in the right hypochondrium Medication: Oncolytic virus Rigvir Clinical Procedure: Nephro-adrenalectomy Specialty: Oncology Objective Unusual or unexpected effect of treatment Background Renal cell carcinoma is the most commonly diagnosed primary mal...
Article
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Oncolytic viruses are a fast-developing cancer treatment field. Numerous viruses have been tested in clinical trials and three are approved. The first, Rigvir, is an immunomodulator with anti-tumour effect for treatment of cutaneous melanoma, local treatment of skin and subcutaneous metastases of melanoma, for prevention of relapse and metastasis a...
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Colorectal cancer is one of the most commonly diagnosed cancers worldwide. The treatment consists of surgical resection, systemic chemotherapy, and new biological agents. One more recently emerging treatment option is oncolytic virotherapy. Although the use of the new treatment methods shows improved overall and progression-free survival, in genera...
Article
Full-text available
Background: The role of oncolytic viruses in cancer treatment is increasingly studied. The first oncolytic virus (Rigvir®, ECHO-7) was registered in Latvia over a decade ago. In a recent retrospective study Rigvir® decreased mortality 4.39-6.57-fold in stage IB-IIC melanoma patients. The aims of the present study are to test the effect of Rigvir® o...
Article
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Melanoma is considered an aggressive malignancy with a tendency of forming metastasis in the brain. Less than 10% of all melanoma cases present with unknown primary tumor location. This diagnose is yet to be fully understood, because there are only theoretical assumptions about the nature of the disease. Melanoma brain metastases have many severe s...
Article
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Oncolytic virotherapy is a recent addition to cancer treatment. Here, we describe positive treatment outcomes in three patients using Rigvir virotherapy. One of the patients is diagnosed with melanoma stage IV M1c, one with small cell lung cancer stage IIIA, and one with histiocytic sarcoma stage IV. The diagnoses of all patients are verified by hi...
Article
Full-text available
An oncolytic, nonpathogenic ECHO-7 virus adapted for melanoma that has not been genetically modified (Rigvir) is approved and registered for virotherapy, an active and specific immunotherapy, in Latvia since 2004. The present retrospective study was carried out to determine the effectiveness of Rigvir in substage IB, IIA, IIB and IIC melanoma patie...
Patent
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Specifically useful stereoisomers of 1,3-dioxane derivatives are described and their use in the treatment of a disease or condition dependent on PPAR modulation, such as diabetes, cancer, inflammation, neurodegenerative disorders and infections as well as their use in the treatment of a disease related to TP, such as cardiovascular diseases.
Article
This study aimed to characterize the in vitro effect of EV-077, a compound that antagonises the binding of prostanoids and isoprostanes to the thromboxane receptor (TP) and inhibits the thromboxane synthase (TS), on platelet aggregation of patients with type-2 diabetes and coronary artery disease (CAD) on chronic aspirin treatment. The effect of EV...
Article
Purpose: This study was performed to determine the oral pharmacokinetics (PK) of EV-077 and its effects on pharmacodynamic (PD) markers. EV-077 blocks prostanoid-induced and isoprostane-induced cellular activation, and is in development for the treatment of vascular inflammation and associated complications of type-2 diabetes.. Methods: This sin...
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The present review focuses on the roles of thromboxane A2 (TxA2) in arterial thrombosis, atherogenesis, vascular stent-related ischemic events and renal proteinuria. Particular emphasis is laid on therapeutic interventions targeting the TxA2 (TP) receptors and TxA2 synthase (TS), including dual TP-receptor antagonists and TS inhibitors. Their signi...
Data
Food intake in B100/48 (n = 7) and B48 (n = 8) mice. Error bars indicate SD. (18.20 MB TIF)
Article
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Free fatty acids released from adipose tissue affect the synthesis of apolipoprotein B-containing lipoproteins and glucose metabolism in the liver. Whether there also exists a reciprocal metabolic arm affecting energy metabolism in white adipose tissue is unknown. We investigated the effects of apoB-containing lipoproteins on catecholamine-induced...
Article
The need for treatment of obesity and obesity-related diseases, such as type 2 diabetes, has been intensified by the epidemic rise of obesity. Recent advances make possible continuous monitoring of metabolically relevant functions in animals to identify novel thermogenic and anorectic compounds. This unit describes non-invasive in vivo calorimetric...
Article
The aims were to compare the temperature dependence of the metabolic rate in young ob/ob mice with that in mature ob/ob and db/db mice and to examine the effect on the metabolic substrate preference of leptin and etomoxir in ob/ob, C57BL/6J (wild-type), and db/db mice. In vivo oxygen consumption and carbon dioxide production were continuously measu...
Article
The need for treatment of obesity and obesity-related diseases, such as type 2 diabetes, has been intensified by the epidemic rise of obesity (Mokdad et al., 2001). Fortunately, several new therapeutic targets have been identified, including biogenic amines, neuroactive peptides, lipase and amylase inhibitors, as well as induction of thermogenesis...
Article
The present study was performed to compare glucocorticoid levels in obese KKA (y) and ob/ob mice with those in normal C57BL/6J mice, and the effect of high-fat diet on glucocorticoids in KKA (y) and ob/ob mice. Liver, mesenteric and epididymal adipose tissue corticosterone and 11-dehydrocorticosterone concentrations as well as circulating corticost...
Article
Background In rodents, the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) converts inactive 11-dehydrocorticosterone (DHC) into active corticosterone. The mRNA and activity of 11β-HSD1 have been shown to be present in batch-incubated pancreatic islets from the ob/ob mouse. In other tissues, 11β-HSD1 expression has been demonstrated to be...
Article
The present study was performed to compare glucocorticoid levels in obese KKA(y) and ob/ob mice with those in normal C5713L/6J mice, and the effect of high-fat diet on glucocorticoids in KKA(y) and ob/ob mice. Liver, mesenteric and epididymal adipose tissue corticosterone and 11-dehydrocorticosterone concentrations as well as circulating corticoste...
Article
The need for treatment of obesity and obesity-related diseases, such as type 2 diabetes, has been intensified by the epidemic rise of obesity. Recent advances make possible continuous monitoring of metabolically relevant functions in animals to identify novel thermogenic and anorectic compounds. This unit describes non-invasive in vivo calorimetric...
Article
BACKGROUND: In rodents, the enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) converts inactive 11-dehydrocorticosterone (DHC) into active corticosterone. The mRNA and activity of 11beta-HSD1 have been shown to be present in batch-incubated pancreatic islets from the ob/ob mouse. In other tissues, 11beta-HSD1 expression has been demon...
Article
Full-text available
11 beta-Hydroxysteroid dehydrogenase type 1 (11 beta-HSD1) has been proposed as a new target for type 2 diabetes drugs. The aim of the present study was to assess the effects of inhibition of 11 beta-HSD1 on blood glucose levels, glucose tolerance, and insulin sensitivity in mouse models of type 2 diabetes. BVT.2733 is an isoform-selective inhibito...
Article
Full-text available
Current pharmacological treatments for Type II (non-insulin-dependent) diabetes mellitus have various limitations. New treatments are needed to reduce long-term risks for diabetic complications and mortality. We tested a new principle for lowering blood glucose. It is well known that glucocorticoids in excess cause glucose intolerance and insulin r...
Article
The present study was done to characterize a new compound, PNU-171990, 2-diisopropyl aminoethyl 1-phenylcyclopentane carboxylate hydrochloride, with functional smooth muscle selectivity at least as high as tolterodine. In vitro homogenates of guinea pig cerebral cortex, parotid gland, heart, urinary bladder, and Chinese hamster ovary (CHO) cells ex...
Article
Novel antidiabetic arylsulfonamidothiazoles are presented that exert action through selective inhibition of the 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) enzyme, thereby attenuating hepatic gluconeogenesis. The diethylamide derivative 2a was shown to potently inhibit human 11beta-HSD1 (IC(50) = 52 nM), whereas the N-methylpiperazinam...
Article
To establish an in vivo model to screen new muscarinic antagonists for the treatment of overactive urinary bladder and to calculate the respective ID(50) values. The conscious rat cystometry model was modified to determine a complete dose-response curve in each animal. Spontaneous micturition was induced by infusion of room-temperature saline into...
Article
The aim of this study was to investigate the distribution of alpha1- and alpha2-adrenoceptors in the urethra and urinary bladder of the female pig, cat, guinea-pig and rat. The binding distributions of an alpha1-adrenoceptor ligand (3H-prazosin) and an alpha2-adrenoceptor ligand (3H-rauwolscine) were determined using in vitro autoradiography. Autor...
Article
The aim of this study was to test alpha-adrenergic reference agonists for tissue selectivity in the urethra and to pharmacologically characterize the functional alpha-adrenoceptor type of the female rabbit urethra in vivo. The effect of alpha-adrenergic agonists and antagonists on the urethral pressure was compared with that on blood pressure and h...
Article
The aim of the present study is to characterise the contraction-mediating functional alpha-adrenoceptor of the female pig urethra. Alpha-adrenoceptor reference agonists were used to contract the isolated female pig urethra. The relative intrinsic activity was noradrenaline (1.0), phenylephrine (0.91), methoxamine (0.74), (+/-)-3'-(2-amino-1-hydroxy...
Article
The present study was performed to test whether high dose agonist (phenylpropanolamine) administration twice a day causes desensitization of urethral alpha-adrenoceptors in vivo. Urethral pressure was measured on five consecutive days of phenylpropanolamine treatment of the unanaesthetized, conscious dog, and the method is described in detail. Phen...
Article
The subtype of the functional presynaptic autoreceptor in adrenergic nerves of the male guinea-pig urethra was pharmacologically characterised. The urethra was incubated with 3H-noradrenaline and superfused with Tyrode solution in vitro and the fractional secretion of 3H-noradrenaline evoked by 300 electrical shocks at 5 Hz was measured. alpha-Adre...
Article
The experiments were done to investigate the presence and subtype of functionally presynaptic muscarinic receptors in cholinergic nerves of the guinea pig urinary bladder. Bladder strips were incubated with 3H-choline and superfused with Tyrode's solution containing eserine. Secreted 3H-acetylcholine was separated from 3H-choline. The electrically...
Article
: The subtype of the functional presynaptic autoreceptor in adrenergic nerves of the male guinea-pig urethra was pharmacologically characterised. The urethra was incubated with 3H-noradrenaline and superfused with Tyrode solution in vitro and the fractional secretion of 3H-noradrenaline evoked by 300 electrical shocks at 5 Hz was measured. α-Adreno...
Article
1. Presynaptic alpha 2-adrenoceptors in a few tissues have recently been pharmacologically classified in functional studies. 2. Autoreceptors are of alpha 2A-subtype in rabbit occipito-parietal cortex, rat cerebral cortex, vas deferens, submandibular gland, kidney, guinea-pig ileum submucosal arterioles and urethra. 3. Heteroreceptors are of alpha...
Article
1.1. Presynaptic α2-adrenoceptors in a few tissues have recently been pharmacologically classified in functional studies.2.2. Autoreceptors are of α2A-subtype in rabbit occipito-perietal cortex, rat cerebral cortex, vas deferens, submandibular gland, kidney, guinea-pig ileum submucosal arterioles and urethra.3.3. Heteroreceptors are of α2A-subtype...
Article
1. The following experiments were carried out to investigate the presence and type of functional presynaptic receptors in adrenergic nerves of the guinea-pig urethra. 2. The urethra from male guinea-pigs was incubated with [3H]-noradrenaline and superfused with Tyrode solution in vitro. The fractional secretion of [3H]-noradrenaline evoked by 300 e...
Article
Acetylcholine esterase inhibitors block cholinergic neurotransmission. This blockade can be reversed by oximes. However, a universally effective esterase reactivator does not exist. A new H-oxime, HLö 7, was tested on rat diaphragm strips. Electrically evoked contractions were blocked by di-2-propyl fluorophosphate (DFP), tabun, sarin and soman. Wh...
Article
The guinea-pig ileum longitudinal muscle-myenteric plexus preparation, pre-incubated with [3H]choline, was mounted in an organ bath and superfused with Tyrode's solution. [3H]Acetylcholine secretion was evoked by 150 electrical shocks at 0.5 Hz. N6,2'-O-Dibutyryladenosine 3',5'-cyclic monophosphate (dibutyryl cyclic AMP) enhanced the [3H]acetylchol...
Article
The guinea-pig ileum longitudinal muscle-myenteric plexus preparation, preincubated with 3H-choline or 3H-noradrenaline, was mounted in an organ bath and superfused with Tyrode's solution. Alaproclate (2-(4-chlorophenyl)-1,1-dimethyl 2-aminopropanoate) (0.01-0.5 mmol/l) reduced (IC50 = 0.1 mmol/l) and at about 0.5 mmol/l completely blocked the elec...
Article
: The guinea-pig ileum longitudinal muscle-myenteric plexus preparation, preincubated with 3H-choline or 3H-noradrenaline, was mounted in an organ bath and superfused with Tyrode's solution. Alaproclate (2-(4-chlorophenyl)-1,1-dimethyl 2-aminopropanoate) (0.01-0.5 mmol/l) reduced (IC50 = 0.1 mmol/l) and at about 0.5 mmol/l completely blocked the el...
Article
1. Secretion of [3H]acetylcholine was studied in the guinea-pig ileum longitudinal muscle-myenteric plexus preparation. The transmitter stores of the cholinergic nerves were labelled by pre-incubation with [3H]choline. The preparation was mounted in an organ bath and superfused with Tyrode solution containing hemicholinium-3 and eserine. [3H]Acetyl...
Article
Guinea-pig isolated vas deferens, in which the stores of noradrenaline (NA) had been labelled by preincubation with [3H]NA, was used to study the effects of substitution of chloride with other anions, on transmitter secretion evoked by electrical stimulation of postganglionic sympathetic nerves. Chloride was omitted from the Tyrode's solution and s...
Chapter
Acetylcholine (ACh) secretion from guinea-pig ileum myenteric plexus is affected by muscarinic agents (1, 4, 5, 6, 9, 11). The secretion is also influenced by inhibitors of phosphodiesterase (3, 10, 12). Addition of 8-Br cyclic AMP enhanced the secretion of [3H]-ACh from guinea-pig ileum myenteric plexus, while the 8-Br analog of cyclic GMP was wit...
Article
Unlabelled: In guinea-pig isolated vas deferens moderate cooling (within the range 16-41 degrees C) improved, while further cooling depressed, sympathetic neuromuscular transmission. Moderate cooling: (a) enhanced the contractile responses both to electrical nerve stimulation and (although less strongly) to exogenous noradrenaline or to the adenos...
Article
Secretion of 3H-noradrenaline was evoked by electrical field stimulation (1 Hz, 300 shocks) in guinea-pig ileum myenteric plexus. The role of cyclic nucleotides in the presynaptic receptor-mediated control of 3H-noradrenaline secretion was studied. The secretion of 3H-noradrenaline was maximally enhanced to the same extent, viz. 300-400% of control...
Article
A muscarinic cholinergic ligand, N-methyl-N-(1-methyl-4-pyrrolidino-2-butynyl)-acetamide (Compound BM-5), was shown to act simultaneously as a presynaptic antagonist and as a postsynaptic agonist at peripheral and central muscarinic synapses. In the presence of eserine it enhanced release of [3H]acetylcholine evoked by electrical stimulation in the...
Article
The pharmacological properties of acetylarsenocholine, an arsenic analogue of acetylcholine, were investigated. Acetylarsenocholine behaved as a cholinergic ligand both in the central and peripheral nervous system. It bound to nicotinic receptors in rat medulla-pons with a KD of 15 microM and to muscarinic receptors in rat cerebral cortex with a KD...
Article
The transmitter stores of cholinergic and noradrenergic neurons in guinea-pig ileum myenteric plexus were labelled by preincubation with 3H-choline or 3H-noradrenaline (3H-NA), respectively. Secretion of transmitter was evoked by electrical field stimulation. In the presence (but not in the absence) of eserine (10 microM) the secretion of 3H-acetyl...
Article
The stores of acetylcholine (ACh) of the cholinergic neurons of guinea-pig myenteric plexus were labelled by preincubation with 3H-(methyl)-choline, to examine the dependence of the secretory mechanisms in these nerves, and of their muscarinic 'autoinhibition', on the extracellular calcium concentration. The curves describing the secretion of label...
Article
1. The myenteric plexus-longitudinal muscle preparation of the guinea-pig ileum was incubated with [³H]choline (1·125-1·5 μM), and then superfused with Tyrode solution containing hemicholinium-3 (10 μM). Secretion of [³H]acetylcholine ([³H]ACh) was evoked either (a) by electrical field stimulation (0·5-15 Hz, 150 shocks per period, 0·5 msec), used...
Article
The acetylcholine (ACh) stores of cholinergic neurons of the myenteric plexus of guinea-pig ileum were labelled by preincubation with 3H-(methyl)-choline. The secretion of labelled transmitter evoked by electrical field stimulation at 1 Hz in the presence of eserine increased by 55% after addition of 0.5 mM 8-Br adenosine 3', 5'-cyclic monophosphat...
Article
The muscarinic acetylcholine (ACh) receptor from rat brain has been partially purified and characterized. The molecular weight of the smallest subunit of the receptor protein obtained by a chaotropic agent is 30,000 dalton, while the protein found in sodium dodecyl sulphate polyacrylamide gels has a molecular weight of 80,000 dalton. The isoelectri...
Article
The transmitter stores of cholinergic and noradrenergic neurons in guinea-pig ileum myenteric plexus were labelled by preincubation with 3H-choline or 3H-noradrenaline (3H-NA), respectively. Secretion of transmitter was evoked by electrical field stimulation. In the presence (but not in the absence) of eserine (10 μM) the secretion of 3H-acetylchol...
Chapter
This chapter describes the alpha-adrenoceptor mediated inhibition of noradrenaune secretion. The concept that α2-adrenoceptors located on noradrenergic nerve terminals mediate negative feedback control of the noradrenaline concentration in the neuro-effector gaps has become widely accepted. It is found that if α-adrenoceptors control the secretion...
Article
1. Mechanisms controlling the secretion of [(3)H]noradrenaline from the noradrenergic nerves of guinea-pig isolated vas deferens, prelabelled by incubation with [(3)H]noradrenaline, were studied using (a) different modes of (extramural or transmural) electrical nerve stimulation (a total of 300 shocks of varying strength, and a duration of 2 msec)...
Article
The effects of 3′,5′-cyclic nucleotide phosphodiesterase (PDE) inhibitors and of 8-Br 3′,5′-cyclic nucleotide analogs on nerve-muscle transmission were studied in the guinea-pig vas deferens preincubated with 3H-noradrenaline. 8-Br cyclic AMP and the PDE inhibitors 3-isobutyl-1-methylxanthine (IBMX) and 3-propionyl-4-hydrazinopyrazolopyridine (SQ 2...
Article
Full-text available
A protein capable of binding atropine and (3H)propylbenzilylcholine mustard was solubilized and purified (200-fold) from rat brain. Pronase and trypsin, but not phospholipases, diminished the binding capacity of the solubilized receptor. The molecular weight of the salt-solubilized receptor as determined by gel filtration in the absence of detergen...

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