Immune Regulatory Function of Cancer-Associated Fibroblasts in Non-small Cell Lung Cancer

Background Cancer-associated fibroblasts (CAFs) are key components of the tumor microenvironment and significantly contribute to immune evasion. We investigated the effects of CAFs on the immune function of CD4+ and CD8+ T cells in non-small cell lung cancer (NSCLC). Methods We isolated CAFs and normal fibroblasts (NFs) from tumors and normal lung tissues of NSCLC patients, respectively. CAFs were co-cultured with activated T cells to evaluate their immune regulatory function. We investigated the effect of CAF conditioned medium (CAF-CM) on the cytotoxicity of T cells. CAFs were also co-cultured with activated peripheral blood mononuclear cells and further incubated with cyclooxygenase-2 (COX2) inhibitors to investigate the potential role of COX2 in immune evasion. Results CAFs and NFs were isolated from the lung tissues (n=8) and lymph nodes (n=3) of NSCLC patients. Immune suppressive markers, such as COX2 and programmed death-ligand 1 (PD-L1), were increased in CAFs after co-culture with activated T cells. Interestingly, CAFs promoted the expression of programmed death-1 in CD4+ and CD8+ T cells, and strongly inhibited T cell proliferation in allogenic and autologous pairs of CAFs and T cells. CAF-CM decreased the cytotoxicity of T cells. COX2 inhibitors partially restored the proliferation of CD4+ and CD8+ T cells, and downregulated the expression of COX2, prostaglandin E synthase, prostaglandin E2, and PD-L1 in CAFs. Conclusion CAFs promote immune evasion by suppressing the function of CD4+ and CD8+ T cells via their effects on COX2 and PD-L1 in NSCLC. The immunosuppressive function of CAFs could be alleviated by COX2 inhibitors

Lattice effects on the current-voltage characteristics of superconducting arrays

The lattice effects on the current-voltage characteristics of two-dimensional arrays of resistively shunted Josephson junctions are investigated. The lattice potential energies due to the discrete lattice structure are calculated for several geometries and directions of current injection. We compare the energy barrier for vortex-pair unbinding with the lattice pinning potential, which shows that lattice effects are negligible in the low-current limit as well as in the high-current limit. At intermediate currents, on the other hand, the lattice potential becomes comparable to the barrier height and the lattice effects may be observed in the current-voltage characteristics.Comment: 5 pages including 5 figures in two columns, to appear in Phys. Rev.

Boundary Effects on Dynamic Behavior of Josephson-Junction Arrays

The boundary effects on the current-voltage characteristics in two-dimensional arrays of resistively shunted Josephson junctions are examined. In particular, we consider both the conventional boundary conditions (CBC) and the fluctuating twist boundary conditions (FTBC), and make comparison of the obtained results. It is observed that the CBC, which have been widely adopted in existing simulations, may give a problem in scaling, arising from rather large boundary effects; the FTBC in general turn out to be effective in reducing the finite-size effects, yielding results with good scaling behavior. To resolve the discrepancy between the two boundary conditions, we propose that the proper scaling in the CBC should be performed with the boundary data discarded: This is shown to give results which indeed scale well and are the same as those from the FTBC.Comment: RevTex, Final version to appear in Phys. Rev.

(1S,2R,3R,6R,7S,8R,10S,11S)-13-{[4-(4-Chloro­phen­yl)piperazin-1-yl]meth­yl}-10-hy­droxy-4,9-dimethyl-3,8,15-trioxatetra­cyclo­[10.3.0.02,4.07,9]penta­decan-14-one

The title compound, C25H33ClN2O5, was synthesized from 9α-hy­droxy­parthenolide (9α-hy­droxy-4,8-dimethyl-12-methyl­ene-3,14-dioxatricyclo­[9.3.0.02,4]tetra­dec-7-en-13-one), which was isolated from the chloro­form extract of the aerial parts of Anvillea radiata. The mol­ecule is built up from fused five- and ten-membered rings with two additional ep­oxy ring systems and a chloro­phenyl­piperazine group as a substituent. The ten-membered ring adopts an approximate chair–chair conformation, while the piperazine ring displays a chair conformation and the five-membered ring shows an envelope conformation with the C atom closest to the hy­droxy group forming the flap. The mol­ecular conformation is stabilized by an intra­molecular O—H⋯N hydrogen bond between the hy­droxy group and a piperazine N atom. The crystal structure is stabilized by weak C—H⋯O inter­actions

10α-Hy­droxy-13-{[4-(2-hy­droxy­phen­yl)piperazin-1-yl]meth­yl}-4,9-dimethyl-3,8,15-trioxatetra­cyclo­[10.3.0.02,4.07,9]penta­decan-14-one

The title compound, C25H34N2O6, was synthesized from 9α-hy­droxy­parthenolide (9α-hy­droxy-4,8-dimethyl-12-methyl­ene-3,14-dioxatricyclo­[9.3.0.02,4]tetra­dec-7-en-13-one), which was isolated from the chloro­form extract of the aerial parts of Anvillea radiata. The ten-membered ring adopts an approximate chair–chair conformation, while the piperazine ring displays a near regular chair conformation and the five-membered ring an envelope conformation with the C atom closest to the hy­droxy group forming the flap. The mol­ecular conformation is stabilized by an O—H⋯N hydrogen bond, which generates an S(7) loop, and the crystal structure features weak C—H⋯O inter­actions

Case report: Spontaneous abortion of monoamniotic twins at the third trimester of pregnancy in Camelus dromedarius

Monoamniotic twins develop when a blastocyst spontaneously splits its progenitor cells, and each group of progenitor cells independently grows to become an individual. It is the rarest type of twin pregnancy and usually has significant developmental or congenital abnormalities, a higher rate of abortion, perinatal morbidity, and mortality. There is no information regarding monoamniotic twins in livestock species. Here, we reported a spontaneous abortion of monoamniotic twins in a dromedary camel at 278 days of gestation. Gonadorelin acetate (100 μg) was injected intramuscularly to induce ovulation in the recipient. A 7 days-old embryo produced by somatic cell nuclear transfer was transferred transcervically to the recipient. Early pregnancy was confirmed by an elevated level of serum progesterone followed by ultrasonography at 22 and 44 days after embryo transfer. A single sac was observed on 22 days while twins were evident 44 days after embryo transfer. Pregnancy was periodically monitored by the tail-up phenomenon. A ruptured fetal sac was observed on the ground having two fetuses. On autopsy, full-grown fetuses were found. Their bodies were separated. There was no congenital anomaly or any malformation in the fetuses. According to the reported chronology in human twins, we hypothesized that the blastocyst splitted before 13 days as it was monoamniotic and not conjoined. If the embryo splits within 4 to 8 days, it develops two amniotic sacs, and splitting after 13 days develops conjoined fetuses. To the authors’ knowledge, this is the first reported case of monoamniotic twin abortion in dromedary camels. This report will increase awareness among practicing veterinarians and camel breeders about twin abortions

Health effects from exposure to dental diagnostic X-ray

The purpose of this review is to summarize the results of studies on of the association between exposure to dental X-rays and health risk. To perform the systematic review, We searched the PUBMED, EMBASE, and MEDLINE databases for papers published before December 15, 2016. A total of 2 158 studies, excluding duplicate studies, were found. Two reviewers independently evaluated the eligibility of each study. The final 21 studies were selected after application of exclusion criteria. In terms of health outcomes, there were 10 studies about brain tumors, 5 about thyroid cancer, 3 about tumors of head and neck areas, and 3 related to systemic health. In brain tumor studies, the association between dental X-ray exposure and meningioma was statistically significant in 5 of the 7 studies. In 4 of the 5 thyroid-related studies, there was a significant correlation with dental diagnostic X-rays. In studies on head and neck areas, tumors included laryngeal, parotid gland, and salivary gland cancers. There was also a statistically significant correlation between full-mouth X-rays and salivary gland cancer, but not parotid gland cancer. Health outcomes such as leukemia, low birth weight, cataracts, and thumb carcinomas were also reported. In a few studies examining health effects related to dental X-ray exposure, possibly increased risks of meningioma and thyroid cancer were suggested. More studies with a large population and prospective design are needed to elaborate these associations further

The ASTRO-H X-ray Observatory

The joint JAXA/NASA ASTRO-H mission is the sixth in a series of highly successful X-ray missions initiated by the Institute of Space and Astronautical Science (ISAS). ASTRO-H will investigate the physics of the high-energy universe via a suite of four instruments, covering a very wide energy range, from 0.3 keV to 600 keV. These instruments include a high-resolution, high-throughput spectrometer sensitive over 0.3-2 keV with high spectral resolution of Delta E < 7 eV, enabled by a micro-calorimeter array located in the focal plane of thin-foil X-ray optics; hard X-ray imaging spectrometers covering 5-80 keV, located in the focal plane of multilayer-coated, focusing hard X-ray mirrors; a wide-field imaging spectrometer sensitive over 0.4-12 keV, with an X-ray CCD camera in the focal plane of a soft X-ray telescope; and a non-focusing Compton-camera type soft gamma-ray detector, sensitive in the 40-600 keV band. The simultaneous broad bandpass, coupled with high spectral resolution, will enable the pursuit of a wide variety of important science themes.Comment: 22 pages, 17 figures, Proceedings of the SPIE Astronomical Instrumentation "Space Telescopes and Instrumentation 2012: Ultraviolet to Gamma Ray

Addressing overdiagnosis and overtreatment in cancer: a prescription for change

A vast range of disorders—from indolent to fast-growing lesions—are labelled as cancer. Therefore, we believe that several changes should be made to the approach to cancer screening and care, such as use of new terminology for indolent and precancerous disorders. We propose the term indolent lesion of epithelial origin, or IDLE, for those lesions (currently labelled as cancers) and their precursors that are unlikely to cause harm if they are left untreated. Furthermore, precursors of cancer or high-risk disorders should not have the term cancer in them. The rationale for this change in approach is that indolent lesions with low malignant potential are common, and screening brings indolent lesions and their precursors to clinical attention, which leads to overdiagnosis and, if unrecognised, possible overtreatment. To minimise that potential, new strategies should be adopted to better define and manage IDLEs. Screening guidelines should be revised to lower the chance of detection of minimal-risk IDLEs and inconsequential cancers with the same energy traditionally used to increase the sensitivity of screening tests. Changing the terminology for some of the lesions currently referred to as cancer will allow physicians to shift medicolegal notions and perceived risk to reflect the evolving understanding of biology, be more judicious about when a biopsy should be done, and organise studies and registries that offer observation or less invasive approaches for indolent disease. Emphasis on avoidance of harm while assuring benefit will improve screening and treatment of patients and will be equally effective in the prevention of death from cancer