Carbon-11-thymidine and FDG to measure therapy response

This study was performed to determine if PET imaging with 11C-thymidine could measure tumor response to chemotherapy early after the initiation of treatment. Imaging of deoxyriboneucleic acid biosynthesis, quantitated with 11C-thymidine, was compared with measurements of tumor energetics, obtained by imaging with 18F-fluorodeoxyglucose (FDG). METHODS: We imaged four patients with small cell lung cancer and two with high-grade sarcoma both before and approximately 1 wk after the start of chemotherapy. Thymidine and FDG studies were done on the same day. Tumor uptake was quantified by standardized uptake values (SUVs) for both tracers by the metabolic rate of FDG and thymidine flux constant (K(TdR)) using regions of interest placed on the most active part of the tumor. RESULTS: In the four patients with clinical response to treatment, both thymidine and FDG uptake markedly declined 1 wk after therapy. Thymidine measurements of SUV and K(TdR) declined by 64% +/- 15% and 84% +/- 33%, respectively. FDG SUV and the metabolic rate of FDG declined by 51% +/- 9% and 63% +/- 23%, respectively. In the patient with metastatic small cell lung cancer who had disease progression, the thymidine SUV decreased by only 8% (FDG not done). In a patient with abdominal sarcoma and progressive disease, thymidine SUV was essentially unchanged (declined by 3%), whereas FDG SUV increased by 69%. CONCLUSION: Images show a decline in both cellular energetics and proliferative rate after successful chemotherapy. In the two patients with progressive disease, thymidine uptake was unchanged 1 wk after therapy. In our limited series, K(TdR) measurements showed a complete shutdown in tumor proliferation in patients in whom FDG showed a more limited decrease in glucose metabolism.     

The Clinical Significance of Phosphorylated Heat Shock Protein 27 (HSPB1) in Pancreatic Cancer

Pancreatic cancer is one of most aggressive forms of cancer. After clinical detection it exhibits fast metastatic growth. Heat shock protein 27 (HSP27; HSPB1) has been characterized as a molecular chaperone which modifies the structures and functions of other proteins in cells when they are exposed to various stresses, such as chemotherapy. While the administration of gemcitabine, an anti-tumor drug, has been the standard treatment for patients with advanced pancreatic cancer, accumulating evidence shows that HSP27 plays a key role in the chemosensitivity to gemcitabine. In addition, phosphorylated HSP27 induced by gemcitabine has been associated with the inhibition of pancreatic cancer cell growth. In this review, we summarize the role of phosphorylated HSP27, as well as HSP27, in the regulation of chemosensitivity in pancreatic cancer.     

A handy tool for history keeping of Geant4 tracks - J4HistoryKeeper

The Particle Flow Analysis (PFA) is currently under intense studies as the most promising way to achieve precision jet energy measurements required at the future linear e⁺e⁻ collider. In order to optimize detector configurations and to tune up the PFA it is crucial to identify factors that limit the PFA performance and clarify the fundamental limits on the jet energy resolution that remain even with the perfect PFA and an infinitely granular calorimeter. This necessitates a tool to connect each calorimeter hit in particle showers to its parent charged track, if any, and eventually all the way back to its corresponding primary particle, while identifying possible interactions and decays along the way. In order to realize this with a realistic memory space, we have developed a set of C++ classes that facilitates history keeping of particle tracks within the framework of Geant4. This software tool, hereafter called J4HistoryKeeper, comes in handy in particular when one needs to stop this history keeping for memory space economy at multiple geometrical boundaries beyond which a particle shower is expected to start. In this paper this software tool is described and applied to a generic detector model to demonstrate its functionality.     

Application of Zen sitting principles to microscopic surgery seating

This paper describes the application of an alternative seating concept for surgeons that reflects the research of Zen sitting postures, which require Zazen meditators to maintain fixed postures for long durations. The aim of this alternative approach is to provide sitters with a seat pan with sacral support(1) that provides a more even distribution of seat pressures, induces forward pelvic rotation and improves lumbar, buttock and thigh support. This approach was applied to the development of a chair for microscopic surgery. The experimental chair is a seat pan that closely matches the three-dimensional contours of the user's buttocks. Seat comfort was evaluated by comparing both changes in pelvic tilt and seat pressure distributions using Regionally-Differentiated Pressure Maps (RDPM) with subjective ratings of surgeons while operating in prototype and conventional chairs. Findings include that the sacral support of the prototype chair prevents backward pelvic rotation, as seen in zazen (Zen sitting postures). Preliminary data suggests that the prototype provided greater sitting comfort and support for constrained operating postures than did the conventional chair. These findings support the selective application of concave-shaped seat pans that conform to users' buttocks and reflect Zen sitting principles.     

Palladium on Carbon‐Catalyzed Aqueous Transformation of Primary Alcohols to Carboxylic Acids Based on Dehydrogenation under Mildly Reduced Pressure

The catalytic dehydrogenation of alcohols to carbonyl products is a green sustainable oxidation with no production of waste except for hydrogen, which can be an energy source. Additionally, a reusable heterogeneous catalyst is valuable from the viewpoint of process chemistry and water is a green solvent. We have accomplished the palladium on carbon (Pd/C)‐catalyzed dehydrogenation of primary alcohols to carboxylic acids in water under a mildly reduced pressure (800 hPa). The reduced pressure can be easily controlled by the vacuum controller of the rotary evaporator to remove the excess of generated hydrogen, which causes the reduction (reverse reaction) of aldehydes to alcohols (starting materials) and other undesirable side reactions. The present method is applicable to the reaction of various aliphatic and benzylic alcohols to the corresponding carboxylic acids, and the Pd/C could be reused at least 5 times.

     

Granular-lattice (Avellino) corneal dystrophy

Smooth muscle differentiation in the ovary is rare, and its histopathologic spectrum, including ovarian smooth muscle metaplasia (SMM), has not been well described. The clinicopathologic findings in 48 ovaries with SMM from 40 women are reported. The average age of women with ovarian SMM was 55.6 years (range, 34 to 86 years). Foci of SMM were semiquantitatively characterized as 1+ in 46% (1 to 3 foci), 2+ in 37% (4 to 6 foci), and 3+ in 17% (> 6 foci). SMM was bilateral in 8 (23%) of the 35 patients who had bilateral oophorectomies. SMM was intimately associated with another ovarian process in 28 (58%) cases, including ovarian cysts (11), endometriosis (3), granulosa cell tumors (3), extensive stromal luteinization (1), ovarian fibroma (1), adhesions (1), and folliculogenesis (8). Ovaries with 2+ to 3+ SMM were associated with another ovarian lesion significantly more often than those with 1+ SMM (p < 0.01). Most women with ovarian SMM (86%) also had uterine leiomyomas. Significant endometrial pathology was present in 13 (37%) of 35 simultaneously removed uteri. In conclusion, SMM occurs most often in perimenopausal or postmenopausal women, most of whom also have uterine leiomyomas. Ovarian SMM is usually confined to a few microscopic fields, is bilateral in < 25% of patients, and is often associated with other ovarian lesions.     

Enhanced cellular uptake of lactosomes using cell-penetrating peptides

Polymeric micelles that are composed of synthetic polymers are generally size controllable and can be easily modified for various applications. Lactosomes (A₃B-type) are biodegradable polymeric micelles composed of an amphipathic polymer, including three poly(sarcosine) blocks and a poly(l-lactic acid) block. Lactosomes accumulate in tumors in vivo through the enhanced permeability and retention (EPR) effect, even on frequently administering them. However, lactosomes cannot be efficiently internalized by cells. To improve cellular uptake of lactosomes, cell-penetrating peptide (CPP)-modified lactosomes were prepared. Seven CPPs (including EB1 and Pep1) were used, and most of them improved the cellular uptake efficiency of lactosomes. In particular, EB1- and Pep1-modified lactosomes were efficiently internalized by cells. In addition, by using CPP-modified and photosensitizer-loaded lactosomes, we demonstrated the photoinduced killing of mammalian cells, including human cancer cells. Accumulation of the EB1-modified lactosomes in NCI-N87 tumors was shown by in vivo imaging. Thus, this study demonstrated that the CPP-modified lactosome is a promising drug carrier.     

Transition-Metal-Catalyzed Highly Regio- and Stereoselective Co-Polymerization of Dialkynylbenzene with Benzenedithiol Leading to Poly（Phenylene Vinylene Sulfide）

Co-polymerization of dialkynylbenzene with benzenedithiol proceeds regio- and stereoselectively in the presence of transition metal catalysts, affording the corresponding poly（phenylene vinylene sulfide） in good yield. In the presence of palladium acetate as catalyst, Markovnikov addition takes place selectively, whereas chlorotris（triphenylphosphine）rhodium-catalyzed reaction affords anti-Markovnikov adduct with excellent regio- and stereoselectivity.