Toward the Total Synthesis of Spirastrellolide A. Part 2: Conquest of the Northern Hemisphere

North and South: The unique biological activity of the natural product spirastrellolide A renders it an attractive lead for anticancer agents. The southern hemisphere (C1–C25) and the northern hemisphere (including the chlorinated [5,6,6]-bis-spiroacetal entity and the lateral C42–C47 chain) are prepared by concise and efficient routes. Consequently, the entire carbon framework of this potent phosphatase inhibitor, which contains 21 chiral centers, is prepared in an optically active form, and an important step toward structure determination by total synthesis is achieved

Toward the Total Synthesis of Spirastrellolide A. Part 1: Strategic Considerations and Preparation of the Southern Domain

North and South: The unique biological activity of the natural product spirastrellolide A renders it an attractive lead for anticancer agents. The southern hemisphere (C1–C25) and the northern hemisphere (including the chlorinated [5,6,6]-bis-spiroacetal entity and the lateral C42–C47 chain) are prepared by concise and efficient routes. Consequently, the entire carbon framework of this potent phosphatase inhibitor, which contains 21 chiral centers, is prepared in an optically active form, and an important step toward structure determination by total synthesis is achieved

Poorly differentiated loco-regionally advanced naso – and oropharyngeal carcinoma: results of neoadjuvant chemotherapy followed by radiotherapy

Over the years 1986–1997, at the Centre of Oncology in Kraków, 82 patients (28 women, 54 men; mean age: 50.8 years) with poorly differentiatied naso- and oropharyngeal carcinoma with metastases to regional nodes (stage III and IV) received neoadjuvant chemotherapy followed by teleradiotherapy. The primary tumour was located in the nasopharynx in 57 patients (69.5%), in the tonsil – in 24 (29.3%), and in the base of the tongue (one patient). Chemotherapy cycles consisted of cisplatin in a dose of 100 mg/m2 administered intravenously on the first day, and 5-f1uorouracil in a dose of 1000 mg/m2 over days 1 to 5. Forty-seven (57.3%) patients received 3 cycles, 25 (30.5%) patients – 2 cycles, 8 (9.8%) patients – 1 cycle. After chemotherapy, patients received conventionally fractionated (200 cGy 5x a week) radiotherapy to the primary tumour (50–65 Gy) and regional nodes (50–70 Gy). The therapy was generally well tolerated, however two patients developed fatal late complications. Improvement in therapy results was observed when comparised with a historical group. Five-year overall survival was 52%. The degree of regression (PR + CR), following neoadjuvant chemotherapy, which appeared to depend on the number of chemotherapy cycles, is the main prognostic factor for this group of patients

A használatalapú biztosítás múltja, jelene és jövője

[Cp*RuCl]₄ (1) has previously been shown to be the precatalyst of choice for stereochemically unorthodox trans-hydrometalations of internal alkynes. Experimental and computational data now prove that the alkyne primarily acts as a four-electron donor ligand to the catalytically active metal fragment [Cp*RuCl] but switches to adopt a two-electron donor character once the reagent R₃MH (M = Si, Ge, Sn) enters the ligand sphere. In the stereodetermining step the resulting loaded complex evolves via an inner-sphere mechanism into a ruthenacyclopropene which swiftly transforms into the product. In accord with the low computed barriers, spectral and preparative data show that the reaction is not only possible but sometimes even favored at low temperatures. Importantly, such trans-hydrometalations are distinguished by excellent levels of regioselectivity when unsymmetrical alkynes are used that carry an −OH or −NHR group in vicinity of the triple bond. A nascent hydrogen bridge between the protic substituent and the polarized [Ru–Cl] unit imposes directionality onto the ligand sphere of the relevant intermediates, which ultimately accounts for the selective delivery of the R₃M– group to the acetylene C-atom proximal to the steering substituent. The interligand hydrogen bonding also allows site-selectivity to be harnessed in reactions of polyunsaturated compounds, since propargylic substrates bind more tightly than ordinary alkynes; even the electronically coupled triple bonds of conjugated 1,3-diynes can be faithfully discriminated as long as one of them is propargylic. Finally, properly positioned protic sites lead to a substantially increased substrate scope in that they render even 1,3-enynes, arylalkynes, and electron-rich alkynylated heterocycles amenable to trans-hydrometalation which are otherwise catalyst poisons

First insight into microbial community composition in a phosphogypsum waste heap soil

The aim of this study was to investigate the soil microbial communities of a phosphogypsum waste heap. The soil microbial community structures can differ over time, as they are affected by the changing environmental conditions caused by a long-term exposure to different kinds of pollutions, like is the case of soil in the post-production waste area in Wiślinka (in the northern part of Poland) currently undergoing restoration. Our analyses indicated that the most abundant phyla were Proteobacteria, Acidobacteria, and Actinobacteria, and generally such an abundance is common for most of the studied soils. The most dominant class were Alphaproteobacteria, with their participation in 33.46% of the total reads. Among this class, the most numbered order was Sphingomonadales, whereas among this order the Sphingomonadaceae family was the most abundant one. The Sphingomonadaceae family is currently in the center of interest of many researchers, due to the ability of some of its members to utilize a wide range of naturally occurring organic compounds and many types of environmental contaminants. This kind of knowledge about microbial populations can support efforts in bioremediation and can improve monitoring changes in the contaminated environments

75. Validity of accelerated hyperfractionated conformal radiation therapy and monitoring of treatment results in patients with advanced NSCLC. Assessment of tolerance and early failure

AimThe assessment of the early failure and toxicity of treatment for the advanced NSCLC using the accelerated hyperfractional conformal irradiationMaterial13 patients (12 men, 1woman, aged 50 – 74), in good performance status/70–90 points of Karnofsky scale/were treated.Patients have been irradiated with 15 MV or 6 MV photon two times a day with 6 hours break using 1.25 Gy fraction to total dose 50 Gy. PTV ranged from 599 to 1104 cm3 (mean 858 cm3).MethodsThe mean tumor dimension before and 6 weeks after finishing treatment with the use of CT have been assessed.Results3 early failure have been observed, all outside of PTV. The 2/3 of that recurrence have been recognized by CT. These patients have been ordered to chemotherapy. The mean tumor dimension was equal to 2,38 cm 6 weeks after finishing of treatment. This means 44% regression of the mean tumor dimension. No side effects and deteriorations of performance status have been observed.All patients have finished the treatment, all are in follow up, alive.ConclusionsThe accelerated hyperfractioned regimen can be carried out in outpatients service if PTV is smaller than 1000 cm3.Observed early recurrence two months of follow up are connected with a progression of a tumor outside of irradiated volume

The Use of Muscle Relaxants After Chemotherapy and Radiotherapy

Paweł Radkowski,1– 3 Michał Jacewicz,2 Iwona Podlińska,2 Maria Derkaczew2 1Department of Anaesthesiology and Intensive Care, Regional Specialist Hospital in Olsztyn, Olsztyn, Poland; 2Department of Anaesthesiology and Intensive Care, Faculty of Medicine, Collegium Medicum University of Warmia and Mazury in Olsztyn, Olsztyn, Poland; 3Department of Anaesthesiology and Intensive Care, Hospital zum Heiligen Geist in Fritzlar, Fritzlar, GermanyCorrespondence: Maria Derkaczew, Department of Anaesthesiology and Intensive Care, Faculty of Medicine, Collegium Medicum University of Warmia and Mazury in Olsztyn, Olsztyn, Poland, Email [email protected]: Patients after chemotherapy and radiotherapy while being operated can suffer from different systemic problems, which may complicate the anesthetic management. Some interactions between muscle relaxants and chemotherapeutics can occur.Aim: This article aims to present the use of muscle relaxants in cancer patients who have undergone chemotherapy and radiotherapy.Material and Methods: Our work is based on the available literature and the authors’ experience.Conclusion: Based on our observations and a thorough examination of the medical literature, it is advisable to exercise significant caution when employing muscle relaxants in individuals undergoing chemotherapy and radiotherapy. All muscle relaxants can behave differently after chemotherapy and radiotherapy, and for this reason, practitioners should familiarize themselves with the pharmacodynamics and pharmacokinetics of their chosen muscle relaxant.Keywords: muscle relaxant, chemotherapy, radiotherap

20 Typ z przewagą limfocytów ziarnicy złośliwej: Czy wymaga odmiennego leczenia?

WstępTyp z przewagą limfocytów ziarnicy złośliwej (LP-HD) jest wyróżniany jako odrębna postać histokliniczna. Ponadto wykazuje się duże morfologiczne podobieństwo do chłoniaka nieziarniczego z limfocytów B, który w rozpoznaniach LP-HD LP-HD może stanowić do 10%. Celem pracy jest ocena przebiegu klinicznego i wyniki leczenia chorych na LP-HD.MateriałW Krakowskim Centrum Onkologii w latach 1987–1996 leczono 53 chorych z rozpoznaniem LP-HD, 14 kobiet i 39 mężczyzn (M:K – 2,8:1). Wiek chorych wahał się od 14 do 73 lat, mediana 39 lat. W stopniu zaawansowania I+II było 31 chorych (58,5%), III+IV 22 chorych (41,5%). Objawy B stwierdzono u 13/53 chorych (24,5%), X 10/53 chorych (18,8%), E u 2/53 chorych (3,8%). U 2/31 chorych (6,5%) proces był zlokalizowany w układzie chłonnym przedprzeponowym. W grupie I+II, 1 chory był leczony wyłącznie chemicznie (CHT), 22 chorych leczono wyłącznie CHT, 3 chorych RT i 10 chorych CHT+RT. Czas obserwacji waha się od 16 do 132 miesięcy (mediana 66 miesięcy).WynikiW całej grupie uzyskano 78% 5 – letnich i 71% 10 – letnich przeżyć, w grupie I+II odpowiednio 90% i 78%. W grupie III+IV 5 i 10 – letnie przeżycia wyniosły 62%. Całkowitą regresję po I rzucie leczenia uzyskano u 100% chorych w grupie I+II 4/5 wznów (80%) stwierdzono w układzie chłonnym przedprzeponowym. Czas wystąpienia wznowy wahał się od 14 do 712 miesięcy (mediana 41 miesięcy). U jednego chorego stwierdzono transformację typu LP w LD.U 3/53 chorych (5,6%) stwierdzono w kontroli chłoniaka nieziarniczego (MALT żołądka, nieokreślony chłoniak o wysokim stopniu złośliwości, chłoniak z limfocytów T) w okresie od 13 do 35 miesięcy (mediana 28 miesięcy). W grupie III+IV przeżycie 5 – letnie wyniosło 69% u chorych leczonych CHT i 32% leczonych wyłącznie RT (p = 0,3).Wnioski1.Wyniki leczenia chorych na LP-HD w naszym materiale nie odbiegają od wyników leczenia chorych na klasyczną postać ziarnicy. Ograniczenie zakresu RT w grupie I+II i CHT w grupie III+IV może mieć wpły na pogorszenie wyników leczenia.2.Mimo odrębności morfologicznych typ LP-HD powinien być leczony jak klasyczna postać ziarnicy złośliwej