Sarginių limfmazgių nustatymo metodai, operuojant krūties vėžį: literatūros apžvalga

Introduction. Detecting metastases is an important part of successful breast cancer treatment. Usually, the tumor tissue first spreads to the sentinel lymph nodes. Removal of the latter during surgery and histological examination allows to assess the patient’s di­sease stage, prognosis and treatment. The literature provides more than one approach or a combination of them, allowing us to accurately identify the breast’s sentinel lymph nodes and avoid removing all axillary lymph nodes. Purpose. To review the methods of intraoperative detection of breast sentinel lymph nodes presented in the literature. Research material and methods. Publications were searched using the specialized information search system Google Scholar. Keywords used in the search: breast sentinel lymph nodes, intraoperative detection. After evaluating the exclusion criteria, the review was based on 25 scientific publications. Results. 4 individual measures and 2 combinations of them can be used to detect sentinel breast lymph nodes during surgery. The materials used can be injected in 6 different ways. Conclusions. The combination of technetium-99m radiocolloid and methylene blue can be evaluated as the best method for intraoperative detection of sentinel lymph nodes in breast cancer patients. On the other hand, due to radiation and operating costs, more attention is being paid to the use of indocyanine green, superparamagnetic iron oxide, methylene blue dye, and the detection of metastases without surgery. Superficial methods of injecting the substance should be combined with deep ones due to the possibility of detecting extra-axillary sentinel lymph nodes of the breast. Ultimately, all decisions must be made on a case-by-case basis.Įvadas. Svarbi krūties vėžio sėkmingo gydymo dalis – nustatyti metastazes. Piktybiniai navikai įprastai pirmiausia išplinta į sritinius limfmazgius. Šių limfmazgių pašalinimas operacijos metu ir histologinis tyrimas leidžia įvertinti paciento ligos stadiją, ligos prognozę ir parinkti tinkamą gydymą. Mokslinėje literatūroje aprašomas ne vienas metodas ar jų derinys, padedantys nustatyti sarginius limfmazgius operuojant krūties vėžį ir leidžiantys išvengti visų pažasties limfmazgių pašalinimo. Tikslas. Apžvelgti mokslinėje literatūroje nurodytus metodus krūties sarginiams limfmazgiams intraoperaciškai nustatyti. Tyrimo medžiaga ir metodai. Publikacijų paieška atlikta naudojant specializuotą informacijos paieškos sistemą Google Scholar. Paieškai naudoti reikšminiai žodžių junginiai: „krūties sarginiai limfmazgiai“ (angl. breast sentinel lymph nodes) ir „intraoperacinis nustatymas“ (angl. intraoperative detection). Įvertinus atmetimo kriterijais, apžvalgoje remtasi 25 mokslinėmis publikacijomis. Rezultatai. Atliekant operaciją, sarginiams krūties limfmazgiams nustatyti gali būti panaudoti keturi individualūs metodai ir du jų deriniai. Naudojamos medžiagos gali būti injekuotos šešiais skirtingais būdais. Išvados. Patikimiausiu metodu sarginiams krūties limfmazgiams intraoperaciškai nustatyti laikytina technecio-99m radioaktyviojo koloido ir metileno mėlio kombinacija. Vis dėlto dėl patiriamos radiacijos ir didelių eksploatavimo kaštų ieškoma naujų, pigesnių ir techniškai paprastesnių sarginių limfmazgių nustatymo būdų. Tai galėtų būti indocianino žaliojo, superparamagnetinio geležies oksido, metileno mėlio naudojimas ir metastazių nustatymas neoperuojant. Paviršiniai medžiagos injekcijos būdai turėtų būti derinami su giliaisiais, siekiant aptikti ne tik pažastyje esančius sarginius krūties limfmazgius. Galutiniai sprendimai turi būti priimami atsižvelgiant į konkretų klinikinį atvejį

The Calcineurin Antagonist, RCAN1-4 is Induced by Exhaustive Exercise in Rat Skeletal Muscle

International audienceThe aim of this work was to study the regulation of the calcineurin antagonist regulator of calcineurin 1 (RCAN1) in rat skeletal muscles after exhaustive physical exercise, which is a physiological modulator of oxidative stress. Three skeletal muscles, namely extensor digitorum longus (EDL), gastrocnemius, and soleus, were investigated. Exhaustive exercise increased RCAN1-4 protein levels in EDL and gastrocnemius, but not in soleus. Protein oxidation as an index of oxidative stress was increased in EDL and gastrocnemius, but remained unchanged in soleus. However, lipid peroxidation was increased in all three muscles. CuZnSOD and catalase protein levels were increased at 3 h postexercise in soleus, whereas they remained unchanged in EDL and gastrocnemius. Calcineurin enzymatic activity declined in EDL and gastrocnemius but not in soleus, and its protein expression was decreased in all three muscles. The level of PGC1-α protein remained unchanged, whereas the protein expression of the transcription factor NFATc4 was decreased in all three muscles. Adiponectin expression was increased in all three muscles. RCAN1-4 expression in EDL and gastrocnemius muscles was augmented by the oxidative stress generated from exhaustive exercise. We propose that increased RCAN1-4 expression and the signal transduction pathways it regulates represent important components of the physiological adaptation to exercise-induced oxidative stress

Cellular Heterogeneity and Cooperativity in Glioma Persister Cells Under Temozolomide Treatment

Factor de impacto: 6,684 Q1.We have observed a drug-tolerant/persister state in a human glioblastoma (GBM) cell line after exposure to temozolomide, the standard-of-care chemotherapeutic agent for GBM. We used a multicolor lentiviral genetic barcode labeling to follow cell population evolution during temozolomide treatment. We observed no change in the distribution of the different colored populations of cells in persister or resistant cells suggesting that pre-existing minor subpopulations, which would be expected to be restricted to a single color, were not amplified/selected during the response to the drug. We have previously identified four genes (CHI3L1, FAT2, KLK5, and HB-EGF) that were over-expressed during the persister stage. Single-cell analysis of these four genes indicated that they were expressed in different individual cells ruling out the existence of a single persister-specific clone but suggesting rather a global answer. Even so, the transitory silencing of CHI3L1, FAT2, or KLK5 influenced the expression of the other three genes and the survival of U251 cells in absence of temozolomide. Since proteins encoded by the four genes are all localized in the extracellular matrix or interact within the extracellular compartment, we propose that cellular interactions and communications are important during the persister stage before the acquisition of chemo-resistance. Thus, persisters might be a new therapeutically relevant target in GBM.This research was founded by a grant from the “Ligue contre le Cancer-Grand Ouest” and a Région Pays de la Loire special fund (ERRATA program).S

Intense exercise training induces adaptation in expression and responsiveness of cardiac β-adrenoceptors in diabetic rats

<p>Abstract</p> <p>Background</p> <p>Informations about the effects of intense exercise training on diabetes-induced myocardial dysfunctions are lacking. We have examined the effects of intense exercise training on the cardiac function of diabetic rats, especially focusing on the Langendorff β-adrenergic responsiveness and on the β-adrenoceptors protein expression.</p> <p>Methods</p> <p>Control or Streptozotocin induced-diabetic male Wistar rats were randomly assigned to sedentary or trained groups. The training program consisted of 8 weeks running on a treadmill (10° incline, up to 25 m/min, 60 min/day) and was considered to be intense for diabetic rats.</p> <p>Results</p> <p>This intense exercise training amplified the <it>in vivo </it>diabetes-induced bradycardia. It had no effect on Langendorff basal cardiac contraction and relaxation performances in control and diabetic rats. In diabetic rats, it accentuated the Langendorff reduced responsiveness to β-adrenergic stimulation. It did not blunt the diabetes-induced decrease of β1-adrenoceptors protein expression, displayed a significant decrease in the β2-adrenoceptors protein expression and normalized the β3-adrenoceptors protein expression.</p> <p>Conclusions</p> <p>Intense exercise training accentuated the decrease in the myocardial responsiveness to β-adrenergic stimulation induced by diabetes. This defect stems principally from the β2-adrenoceptors protein expression reduction. Thus, these results demonstrate that intense exercise training induces specific effects on the β-adrenergic system in diabetes.</p

PRAF3 induces apoptosis and inhibits migration and invasion in human esophageal squamous cell carcinoma

<p>Abstract</p> <p>Background</p> <p>Prenylated Rab acceptor 1 domain family member 3 (PRAF3) is involved in the regulation of many cellular processes including apoptosis, migration and invasion. This study was conducted to investigate the effect of PRAF3 on apoptosis, migration and invasion in human esophageal squamous cell carcinoma (ESCC).</p> <p>Methods</p> <p>The expression of <it>PRAF3 </it>mRNA and protein in primary ESCC and the matched normal tissues (57cases) was determined by quantitative RT-PCR and Western blot. Immunohistochemical analysis of PRAF3 expression was carried out in paraffin-embedded sections of ESCC and correlated with clinical features. The role of PRAF3 in apoptosis, migration and invasion was studied in ESCC cell lines of Eca109 and TE-1 through the adenovirus mediated PRAF3 gene transfer. The effect of PRAF3 on apoptosis was analyzed by annexin V-FITC assay. The regulation of PRAF3 on migration was determined by transwell and wounding healing assay, while the cellular invasion was analyzed by matrigel-coated transwell assay.</p> <p>Results</p> <p>We found that the expression of PRAF3 was significantly down-regulated in ESCC tissue compared with the matched normal tissue and was correlated with the clinical features of pathological grade, tumor stage and lymph node metastasis. Moreover, overexpression of PRAF3 induced cell apoptosis through both caspase-8 and caspase-9 dependent pathways, and inhibited cell migration and invasion by suppressing the activity of both MMP-2 and MMP-9 in human ESCC cell lines.</p> <p>Conclusions</p> <p>Our data suggest that PRAF3 plays an important role in the regulation of tumor progression and metastasis and serves as a tumor suppressor in human ESCC. We propose that PRAF3 might be used as a potential therapeutic agent for human ESCC.</p

Gene expression profiling in sinonasal adenocarcinoma

<p>Abstract</p> <p>Background</p> <p>Sinonasal adenocarcinomas are uncommon tumors which develop in the ethmoid sinus after exposure to wood dust. Although the etiology of these tumors is well defined, very little is known about their molecular basis and no diagnostic tool exists for their early detection in high-risk workers.</p> <p>Methods</p> <p>To identify genes involved in this disease, we performed gene expression profiling using cancer-dedicated microarrays, on nine matched samples of sinonasal adenocarcinomas and non-tumor sinusal tissue. Microarray results were validated by quantitative RT-PCR and immunohistochemistry on two additional sets of tumors.</p> <p>Results</p> <p>Among the genes with significant differential expression we selected <it>LGALS4, ACS5, CLU, SRI and CCT5 </it>for further exploration. The overexpression of <it>LGALS4, ACS5, SRI</it>, <it>CCT5 </it>and the downregulation of <it>CLU </it>were confirmed by quantitative RT-PCR. Immunohistochemistry was performed for LGALS4 (Galectin 4), ACS5 (Acyl-CoA synthetase) and CLU (Clusterin) proteins: LGALS4 was highly up-regulated, particularly in the most differentiated tumors, while CLU was lost in all tumors. The expression of ACS5, was more heterogeneous and no correlation was observed with the tumor type.</p> <p>Conclusion</p> <p>Within our microarray study in sinonasal adenocarcinoma we identified two proteins, LGALS4 and CLU, that were significantly differentially expressed in tumors compared to normal tissue. A further evaluation on a new set of tissues, including precancerous stages and low grade tumors, is necessary to evaluate the possibility of using them as diagnostic markers.</p

Antagonizing retinoic acid receptors increases myeloid cell production by cultured human hematopoietic stem cells

Activities of the retinoic acid receptor (RAR)α and RARγ are important to hematopoiesis. Here, we have investigated the effects of receptor selective agonists and antagonists on the primitive human hematopoietic cell lines KG1 and NB-4 and purified normal human hematopoietic stem cells (HSCs). Agonizing RARα (by AGN195183) was effective in driving neutrophil differentiation of NB-4 cells and this agonist synergized with a low amount (10 nM) of 1α,25-dihydroxyvitamin D(3) to drive monocyte differentiation of NB-4 and KG1 cells. Treatment of cultures of human HSCs (supplemented with stem cell factor ± interleukin 3) with an antagonist of all RARs (AGN194310) or of RARα (AGN196996) prolonged the lifespan of cultures, up to 55 days, and increased the production of neutrophils and monocytes. Slowing down of cell differentiation was not observed, and instead, hematopoietic stem and progenitor cells had expanded in number. Antagonism of RARγ (by AGN205728) did not affect cultures of HSCs. Studies of CV-1 and LNCaP cells transfected with RAR expression vectors and a reporter vector revealed that RARγ and RARβ are activated by sub-nM all-trans retinoic acid (EC(50)–0.3 nM): ~50-fold more is required for activation of RARα (EC(50)–16 nM). These findings further support the notion that the balance of expression and activity of RARα and RARγ are important to hematopoietic stem and progenitor cell expansion and differentiation