Statins and colorectal cancer

Statins are naturally occurring compounds that inhibit the enzyme 3-hydroxy-3-methyl-glutaryl-CoA reductase. Through their beneficial management of the body’s lipid metabolism, they are widely used medicinal drugs employed extensively in the primary and secondary prevention of cardiovascular disease. In addition, many studies to date have shown the therapeutic advantages derived from using statins in conditions such as endometriosis, osteoporosis, polycystic ovary syndrome and rheumatic disease. Due to the steady increase of cancer morbidity rates, as demonstrated by epidemiological data, the putative role of statins in treating or preventing cancer has been ever more frequently investigated; including for colorectal cancer. This paper attempts to bring together current knowledge/ evidence on statin therapy targeted at the development, disease course and treatment of colorectal cancer, both in terms of epidemiological findings and clinical observations. Because of the reported link between metabolic disorders and the development of colorectal cancer, particular focus is given to the effects of statins on signalling pathways involving insulin-like growth factors (IGFs)

Przyczyny i konsekwencje upadków w chorobie Parkinsona – badanie prospektywne

Background and purpose Falls are common events in Parkinson disease (PD) but only a few prospective studies have focused on causes and consequences of falls in PD patients. The aim of the study was prospective analysis of direct causes and consequences of falls in PD patients in comparison to the control group. Material and methods One hundred PD patients and 55 age-matched controls were enrolled in the study. The diagnostic workup in all patients included neurological examination, Unified Parkinson's Disease Rating Scale, magnetic resonance imaging, electroencephalography, ultrasonography, otolaryngological, ophthalmological and autonomic function examination. During 12 months of follow-up, falls were registered in both groups, direct causes were classified according to the St. Louis and Olanow classification, and consequences were established. Results Falls occurred in 54% of PD patients and in 18% of control subjects. Analysis of direct causes of falls revealed that sudden falls were the most common (31%), followed by episodes of freezing and festination (19.6%), neurological and sensory disturbances (mostly vertigo) (12%), environmental factors (12%), postural instability (11%), orthostatic hypotension (4%), and severe dyskinesia (3.6%); 6.19% of falls were unclassified; 22% of patients had the same etiology of subsequent falls. In PD patients, intrinsic factors were dominant, whereas in the control group intrinsic and extrinsic factors occurred with the same frequency. Every third fall intensified fear of walking. 34% of falls caused injuries; among them bruises of body parts other than the head were most frequent. Conclusions Intrinsic factors are the most common causes of falls in PD. Every third fall intensifies fear of walking and causes injuries.Wstęp i cel pracy Upadki są częstymi objawami choroby Parkinsona (ChP). Dotychczas jednak tylko w kilku badaniach oceniano przyczyny i konsekwencje upadków w ChP. Celem badania była prospektywna analiza przyczyn bezpośrednich oraz konsekwencji upadków u pacjentów z ChP w porównaniu z grupą kontrolną. Materiał i metody Do badania zostało włączonych 100 chorych na ChP oraz 55 dobranych pod względem wieku osób z grupy kontrolnej. U wszystkich chorych przeprowadzono badanie neurologiczne, ocenę za pomocą Unified Parkinson's Disease Rating Scale, badanie za pomocą rezonansu magnetycznego, elektroencefalografię i ultrasonografię, badanie otolaryngologiczne i okulistyczne oraz badanie czynności autonomicznych. Podczas 12-miesięcznej obserwacji upadki rejestrowano w obu badanych grupach. Przyczyny bezpośrednie upadków podzielono zgodnie z klasyfikacją St. Louis i Olanowa, określano także konsekwencje upadków. Wyniki Upadki wystąpiły u 54% chorych na ChP i 18% osób z grupy kontrolnej. Najczęstsze były upadki nagłe (31%), następnie epizody zamrożeń i dreptania (19,6%), zaburzenia neurologiczne i czuciowe (zawroty głowy) (12%), czynniki zewnętrzne (12%), niestabilność postawy (11%), niedociśnienie ortostatyczne (4%), nasilone dyskinezy (3,6%). Upadki niesklasyfikowane stanowiły 6,19%. U 22% chorych etiologia kolejnych upadków była jednakowa. U chorych na ChP dominowały czynniki wewnętrzne, a w grupie kontrolnej częstości czynników wewnętrznych i zewnętrznych były podobne. Co trzeci upadek nasilał lęk przed chodzeniem, 34% upadków powodowało obrażenia, najczęściej sduczenia. Wnioski Czynniki wewnętrzne są najczęstszymi przyczynami upadków w ChP. Co trzeci upadek nasila lęk przed chodzeniem oraz powoduje obrażenia

Causes and consequences of falls in Parkinson disease patients in a prospective study

Background and purpose: Falls are common events in Parkinson disease (PD) but only a few prospective studies have focused on causes and consequences of falls in PD patients. The aim of the study was prospective analysis of direct causes and consequences of falls in PD patients in comparison to the control group. Material and methods: One hundred PD patients and 55 age-matched controls were enrolled in the study. The diagnostic workup in all patients included neurological examination, Unified Parkinson’s Disease Rating Scale, magnetic resonance imaging, electroencephalography, ultrasonography, otolaryngological, ophthalmological and autonomic function examination. During 12 months of follow-up, falls were registered in both groups, direct causes were classified according to the St. Louis and Olanow classification, and consequences were established. Results: Falls occurred in 54% of PD patients and in 18% of control subjects. Analysis of direct causes of falls revealed that sudden falls were the most common (31%), followed by episodes of freezing and festination (19.6%), neurological and sensory disturbances (mostly vertigo) (12%), environmental factors (12%), postural instability (11%), orthostatic hypotension (4%), and severe dyskinesia (3.6%); 6.19% of falls were unclassified; 22% of patients had the same etiology of subsequent falls. In PD patients, intrinsic factors were dominant, whereas in the control group intrinsic and extrinsic factors occurred with the same frequency. Every third fall intensified fear of walking. 34% of falls caused injuries; among them bruises of body parts other than the head were most frequent. Conclusions: Intrinsic factors are the most common causes of falls in PD. Every third fall intensifies fear of walking and causes injuries

Statyny w raku jelita grubego

Statyny należą do związkow chemicznych pochodzenia naturalnego, wykazujących aktywność inhibicyjną wobec enzymu redukatazy 3-hydroksy-3-metylo-glutarylo-CoA. Tym samym, poprzez wywieranie korzystnego efektu na gospodarkę lipidową organizmu, należą do powszechnie stosowanych lekow w prewencji pierwotnej i wtornej chorob układu sercowo-naczyniowego. Ponadto w wielu dotychczasowych badaniach podejmowano temat korzyści terapii statynami w takich schorzeniach jak: endometrioza, osteoporoza, zespoł policystycznych jajnikow i choroby reumatyczne. Z uwagi na niekorzystne dane epidemiologiczne, wskazujące na stały wzrost zachorowalności na nowotwory złośliwe, coraz częściej podejmowane są badania na temat ewentualnej pozytywnej roli statyn w profilaktyce i leczeniu chorob onkologicznych, w tym raka jelita grubego. W prezentowanej pracy autorzy podjęli probę syntezy dotychczasowej wiedzy na temat znaczenia terapii statynami w rozwoju, przebiegu i leczeniu raka jelita grubego, z uwzględnieniem danych epidemiologicznych oraz obserwacji klinicznych. Z uwagi na udokumentowany związek występowania zaburzeń metabolicznych z rozwojem raka jelita grubego szczegolny nacisk położono na analizę udziału statyn w szlakach sygnałowych związanych z insulinopodobnymi czynnikami wzrostu

Solid-Phase Synthesis of Arylpiperazine Derivatives and Implementation of the Distributed Drug Discovery (D3) Project in the Search for CNS Agents

We have successfully implemented the concept of Distributed Drug Discovery (D3) in the search for CNS agents. Herein, we demonstrate, for the first time, student engagement from different sites around the globe in the development of new biologically active compounds. As an outcome we have synthesized a 24-membered library of arylpiperazine derivatives targeted to 5-HT1A and 5-HT2A receptors. The synthesis was simultaneously performed on BAL-MBHA-PS resin in Poland and the United States, and on BAL-PS-SynPhase Lanterns in France. The D3 project strategy opens the possibility of obtaining potent 5-HT1A/5-HT2A agents in a distributed fashion. While the biological testing is still centralized, this combination of distributed synthesis with screening will enable a D3 network of students world-wide to participate, as part of their education, in the synthesis and testing of this class of biologically active compounds

Aktywność rybocyklibu i hormonoterapii u chorych na zaawansowanego, luminalnego HER2-ujemnego raka piersi w praktyce klinicznej — opisy przypadków

Selektywne inhibitory kinaz zależnych od cyklin CDK4 i CDK 6 (iCDK4/6, cyclin-dependent kinase inhibitors) — palbocyklib, rybocyklib i abemacyklib — stanowią nową grupę leków zmniejszających proliferację przez zahamowanie przejścia komórek w cyklu komórkowym z fazy G1 do S. Leki te są obecnie standardem postępowania u chorych na miejscowo zaawansowanego lub uogólnionego raka piersi z ekspresją receptorów estrogenowych (ER, estrogen receptor) i progesteronowych (PR, progesterone receptor) bez nadekspresji receptora naskórkowego czynnika wzrostu typu 2 (HER2, human epidermal growth factor receptor type 2) w skojarzeniu z jednym z inhibitorów aromatazy lub fulwestrantem w pierwszej linii leczenia lub po niepowodzeniu wcześniejszej hormonoterapii. W niniejszym opracowaniu przedstawiono opisy przypadków chorych na raka piersi leczonych rybocyklibem w skojarzeniu z hormonoterapią w ramach programu rozszerzonego dostępu (MAP, managed access program)

Antioxidative assessment of new trans-palladium (II) complexes in head and neck cancer

Background: Head and neck neoplasms stand for 6% of all malignant neoplasms worldwide. Chemotherapy has limited use due to the biological properties of the tumor (in the majority of cases moderately and poorly differentiated squamous cell carcinoma). The fundamental molecule used in treatment is cisplatin and its derivates, that can be associated with fluorouracil. The new chemotherapeutic agents are not in common use during the treatment of head and neck malignancies. However, the use of low molecular weight complexes Pd (II) carries the potential of being more effective in therapy. Material and Methods: Fifty-one patients, 30 men and 21 women (aged 52.9 ± 12.1 years) with head and neck cancer were included in the study. Fifty-one healthy subjects, 31 men and 20 women, (aged 54.1 ± 14.7 years) years formed the control group. Antioxidant enzymes, superoxide dismutase, and catalase activities in erythrocytes were examined. Results: An increased level of antioxidant enzymes was seen in the blood samples from patients with head and neck cancer after incubation with Pd (II) complex. In the group we obtained a statistically significant result p = <0.001. Discussion: That project may contribute to the development of new, more efficient head and neck cancer treatment strategies. In our opinion, the results can be used in the future to develop a valuable prognostic marker of the disease. This is important because the initial phase of cancer is asymptomatic. The search for factors involved in pathogenesis translates into economic benefits and makes therapy more effectiveness through the reduction of treatment expenses

Satisfaction and discontent of Polish patients with biological therapy of rheumatic diseases : results of a multi-center questionnaire study

Objectives: Biologics are medications widely applied in the management of inflammatory rheumatic diseases. The drugs were found to be effective but their application is associated with some disadvantages. Medication with biologics is relatively expensive, and in Poland, it is carried out in specialized centers. The study was designed to evaluate various aspects of satisfaction and dissatisfaction of Polish patients treated with biologics. Material and methods: An anonymous questionnaire was distributed in 23 Polish rheumatological centers involved in the treatment; 1212 returned questionnaires were used for analysis. Responses were received from 606 patients with rheumatoid arthritis, 427 with ankylosing spondylitis, 117 psoriatic arthritis, and 62 adult patients with juvenile idiopathic arthritis (in whom administration of the drugs had been introduced before they were 18 years old). The investigated group constituted about one-fifth of all rheumatic patients on biologics in Poland. Results: A beneficial or very beneficial influence of the medication on the state of physical health was found mostly in patients with rheumatoid arthritis (51.3 and 30.5%) and ankylosing spondylitis (51.0 and 36.8%). Family life was improved by the treatment especially in patients with ankylosing spondylitis (40.7 and 35.6% beneficial and very beneficial, respectively), sleep quality and sexual life mostly in those with ankylosing spondylitis (beneficial/very beneficial influence 41.5/38.4, and 38.7/23.9, respectively). There was a rather small influence of biological treatment on the financial situation of the patients. In general, satisfaction with the treatment was evaluated as positive or very positive in 88% of all investigated patients. In a significant part of the patients, transportation to the medical center was considered as a disadvantage of the treatment. About one-third of the patients considered laboratory and imaging tests to be done before initiation of the medication as a difficulty, and for about 40% waiting time for qualification for the medication was a significant disadvantage. The route of drug administration was without importance for 4/5 of the patients. Conclusions: Summing up, the results were similar in the patients suffering from various diseases although those with psoriatic arthritis felt the highest satisfaction (possibly due to the positive aesthetic effect), and those with ankylosing spondylitis had significant improvement in sexual life (probably due to younger age). Relatively low satisfaction was found in patients with juvenile idiopathic arthritis. There was a small influence of medication on financial status of the patients. Application of biologics has few disadvantages and most of them are associated with the organization of health services (waiting time for the tests, transportation to the medical centers)