Advancements of ALK inhibition of non-small cell lung cancer: a literature review.

Background And Objective: The therapeutic landscape for non-small cell lung cancer (NSCLC) has evolved considerably in the last few years. The targeted drugs and molecular diagnostics have been developed together at a fast pace. This narrative review explores the evolution of anaplastic lymphoma kinase (ALK) targeting therapies from discovering the ALK protein, molecular tests, present clinical trial data and future perspectives.

The Role of MET Inhibitor Therapies in the Treatment of Advanced Non-Small Cell Lung Cancer.

: Non-small cell lung cancer (NSCLC) is the second most common cancer globally. The mesenchymal-epithelial transition (MET) proto-oncogene can be targeted in NSCLC patients. : We performed a literature search on PubMed in December 2019 for studies on MET inhibitors and NSCLC.

Recurrent uterine serous carcinoma with a germline pathogenic variant treated using olaparib: A case report.

A germline pathogenic variant in was secondarily found through genomic sequencing of uterine serous carcinoma. Clinical response to olaparib was observed in recurrent uterine serous carcinoma with a germline mutation. Here, we report, for the first time, a long-term clinical response to olaparib in a patient with uterine serous carcinoma and a germline pathogenic variant.

Magnetic resonance imaging of the breast: role in the evaluation of ductal carcinoma in situ.

Ductal carcinoma in situ (DCIS) is a precursor mammary lesion whose malignant cells do not extend beyond the basement membrane and presents a risk of progression to malignant disease. Its early detection increased with screening mammography. The objective of this study was to review the literature on the main presentations of DCIS on magnetic resonance imaging (MRI), through searches of the Medline/PubMed, Latin-American and Caribbean Center on Health Sciences Information (Lilacs), and Scientific Electronic Library Online (SciELO) databases.

Task-dependent recurrent dynamics in visual cortex.

The capacity for flexible sensory-action association in animals has been related to context-dependent attractor dynamics outside the sensory cortices. Here, we report a line of evidence that flexibly modulated attractor dynamics during task switching are already present in the higher visual cortex in macaque monkeys. With a nonlinear decoding approach, we can extract the particular aspect of the neural population response that reflects the task-induced emergence of bistable attractor dynamics in a neural population, which could be obscured by standard unsupervised dimensionality reductions such as PCA.

Population Code Dynamics in Categorical Perception.

Categorical perception is a ubiquitous function in sensory information processing, and is reported to have important influences on the recognition of presented and/or memorized stimuli. However, such complex interactions among categorical perception and other aspects of sensory processing have not been explained well in a unified manner. Here, we propose a recurrent neural network model to process categorical information of stimuli, which approximately realizes a hierarchical Bayesian estimation on stimuli.

Effects of androgens on the development of nuptial coloration and chromatophores in the bitterling Rhodeus ocellatus ocellatus.

Sexually mature male bitterlings, Rhodeus ocellatus ocellatus, exhibit distinct nuptial color, whereas females maintain a body color similar to that of juveniles. In the present study, body color and chromatophores were compared between male and female bitterlings, and the effects of androgens on body color and chromatophore densities were examined in females to clarify the role of androgen in the development of nuptial coloration and chromatophores. Males showed green, blue, and red color in specific regions of their skin and red color on the dorsal and caudal fins; females showed a subdued silver body color.

Immunochemical characteristics of a novel cell death receptor and a decoy receptor on granulosa cells of porcine ovarian follicles.

Previously, we prepared an IgM monoclonal antibody(PFG-1) which specifically recognized a cell-membraneglycoprotein (PFG-1 antigen; 55 kD, pI 5.9),immunohistochemically reacted with granulosa cells ofhealthy follicles but not of atretic follicles, andinduced granulosa cell apoptosis. In the presentstudy, an IgM monoclonal antibody (PFG-3) capable ofinducing granulosa cell apoptosis and an IgGmonoclonal antibody (PFG-4) not capable of inducingapoptosis were produced against granulosa cellsprepared from healthy antral follicles of porcineovaries.

Potent antinociceptive effects of TRK-820, a novel kappa-opioid receptor agonist.

TRK-820, a new type of 4,5-epoxymorphinan derivative, was investigated in vivo for antinociceptive activities and its selectivity on various opioid receptors in mice. TRK-820 given s.c.

Elevation of serum hepatic aminotransferases during treatment of rheumatoid arthritis with low-dose methotrexate. Risk factors and response to folic acid.

Sixty-six rheumatoid arthritis (RA) patients were analyzed retrospectively to assess the incidence and risk factors for elevation of serum hepatic aminotransferases during methotrexate (MTX) therapy. The effect of folate supplementation on serum ALT and RA activity was evaluated prospectively in 14 patients who showed a sustained high serum level of ALT. The frequency of elevation of serum AST or ALT was 4-5 times greater than in patients taking other DMARDs.

Up-regulation of the alpha2,6-sialyltransferase messenger ribonucleic acid increases glycoconjugates containing alpha2, 6-linked sialic acid residues in granulosa cells during follicular atresia of porcine ovaries.

The sugar chains in cellular glycoconjugates have many biological functions. Extensive morphological development and remodeling occur in the ovary of female animals. This caused us to study glycobiological characteristics of ovarian cells, particularly granulosa cells that undergo apoptosis during follicular atresia.

Rational drug design and synthesis of a highly selective nonpeptide delta-opioid agonist, (4aS*,12aR*)-4a-(3-hydroxyphenyl)-2-methyl- 1,2,3,4,4a,5,12,12a-octahydropyrido[3,4-b]acridine (TAN-67).

We designed highly selective non-peptide agonists for the delta-opioid receptor. On the basis of the "message-address" concept in this field and the accessory site hypothesis, a novel class of heterocycle-fused octahydroisoquinoline derivatives were synthesized. One of these compounds [(4aS*,12aR*)-4a-(3-hydroxyphenyl)-2-methyl-1,2,3,4,4a,5,12, 12a -octahydropyrido[3,4-b]acridine, TAN-67 (2)] showed high selectivity for the delta-opioid receptor (Ki = 1.

Clinical significance of immunoglobulin A antiphospholipid antibodies: possible association with skin manifestations and small vessel vasculitis.

Objective: To clarify whether immunoglobulin A (IgA) antiphospholipid antibodies (aPL) are an independent risk factor for specific manifestations of collagen vascular diseases.

Methods: We determined IgG, IgM, and IgA anticardiolipin antibodies (aCL) and lupus anticoagulant (LAC) in 77 patients with various collagen diseases. Fifty-four patients who had positive results for either or both antibody classes were compared to 23 patients with systemic lupus erythematosus who had none of these antibodies.

[Clinical relapse of rheumatoid arthritis (escape phenomenon) during low-dose methotrexate therapy].

Objective: To clarify the incidence and background of clinical relapse (escape phenomenon) during low-dose methotrexate therapy for rheumatoid arthritis.

Methods: Seventy one patients with rheumatoid arthritis (RA) were analyzed. They were started on therapy with methotrexate (MTX) between April 1, 1991 and May 30, 1995.

Discovery of a structurally novel opioid kappa-agonist derived from 4,5-epoxymorphinan.

A new type of kappa-agonist, 17-cyclopropylmethyl-3, 14 beta-dihydroxy-4,5 alpha-epoxy-6 beta-[N-methyl-trans-3-(3-furyl) acrylamido]morphinan hydrochloride (1, TRK-820), was discovered by a new working hypothesis. The "message-address concept" for opioid antagonists and the "accessory site" for general antagonists were applied to design TRK-820. A unique structural feature of TRK-820, which is different from other prototypical kappa-opioid receptor agonists, is the existence of the 4,5-epoxymorphinan structure with a tyrosine-glysine moiety for endogenous opioid peptides such as dynorphins.

[Evaluation of sensitivity and specificity of confirmatory assays for lupus anticoagulant (LA) detection].

To evaluate the sensitivity and specificity of confirmatory assays for LA detection, we performed the platelet neutralization procedure (PNP), diluted Russell's viper venom time (dRVVT) confirmatory assay (the ratio of LA-screen and LA-confirm:S/C), and specific hexagonal phase neutralization test (StaLA) on, plasma samples 43 LA-positive in either the ratio of dilute APTT and APTT(dAPTT/APTT) or dRVVT(LA-screen). The sensitivity and the specificity were evaluated by 4 different analyses based on, 1) maximal plasma dilution, 2) correlation between the screening assays and these confirmatory assays, 3) ratio of LA-positive in the confirmatory assays, and 4) receiver operation characteristic (ROC) method. All 4 analyses showed that sensitivity was in the order of PNP > S/C > Staclot-LA.

[Sex difference of free erythrocyte protoporphyrin (FEP) level. III. Effect of estradiol on porphyrin metabolism, especially in FEP, in lead poisoned rats].

An experimental study of sex hormone on FEP level in rats was conducted to clarify sex difference of FEP level. A total of 42 male Donryu rats were divided into 7 groups; group I (control 1; olive oil injection without castration), group II (control 2; olive oil alone), group III (EL; estradiol in olive oil, 50 micrograms/kg.BW), group IV (EH; estradiol in olive oil, 250 micrograms/kg.

Development of skill of children in the performance of the family computer game "Super Mario Brothers".

The development of skill of children in the performance of a family computer game (Super Mario Brothers) was investigated among three groups of different age: kindergarten children (6 years old) and primary school children (9 and 12 years old). The skill to perform the game with either hand was evaluated by the mean scores gained by the children. In the normal (right and dominant) situation, the mean score improved significantly with advancement of age.

[Midluteal progesterone/estradiol ratio as an indicator of pregnancy potential].

In an effort to determine the reliability of the midluteal progesterone(P)/estradiol(E2) ratio as an index of the potential for conception, we measured the midluteal P and E2 levels in 76 infertile women who had been treated at our infertility clinic. This parameter in conception cycles was compared with that in non-conception cycles. Eighty cycles of the 76 women were classified into two groups, depending upon whether pregnancy occurred or not.

[Role of progesterone in the ovulatory process of PMSG/hCG treated immature female rats].

To determine exactly when progesterone (P) acts as a most important mediator in the ovulatory process, a dose of 10mg/kg of RU486, an antiprogesterone, was administered to PMSG/hCG treated immature female rats (22 days old) at 0 (RU0 groups), 2 (RU2 group), 4,6,8 or 10 hours after an hCG injection, respectively. In the RU0 groups, the ovulatory effect of P was investigated at 0.2 (P2 group), 4 (P4 group), 6 or 8 hours after the hCG injection.

[Effect of RU 486 on glycogen metabolism in endometrium].

To elucidate the effect of the antiprogesterone steroid RU 486 (RU) on endometrial glycogen metabolism, a dose of 30 mg/kg of the agent was administered to pregnant rats on Day 2 (group 1) or Day 4 (group 2) of pregnancy, and glycogen content, glycogen synthetase (GS) and glycogen phosphorylase (GP) activities in the endometrium were investigated on Day 6. In addition, serum ovarian steroid hormones and the number of implantation sites were evaluated. The glycogen content in the endometrium in group 1 and group 2 decreased significantly (p less than 0.

Effect of RU 486 on luteal function in the early pregnant rat.

A dose of 30 mg RU 486/kg, an antiprogesterone, was administered to pregnant rats on Day 2 (Group 1) or Day 4 (Group 2) of pregnancy. RU 486 significantly changed serum progesterone and oestradiol concentrations and luteal 3 beta-HSD and 20 alpha-HSD activities in Group 1, and implantation was significantly inhibited. The luteal 3 beta-HSD activity in Group 2 rats on Day 6 was significantly (P less than 0.