Malignus emlotumor? Gyulladásos emloelváltozás? Ritka benignus kórkép?

Case-report: Rosai-Dorfman disease, also known as sinus histiocytosis with massive lymphadenopathy is a rare, benign non-Langerhans cell histiocytosis, that typically involves the lymph nodes, but may also involve extranodal sites. We present a 58- years- old female patient who complained of a palpable mass in her left breast surrounded by 15-20 livid cutaneous lesions, resembling malignant breast cancer with cutaneous metastasis. Despite of core biopsy of the tumor and excisional biopsy one of the lesions, correct diagnosis of RDD was achieved only by complete pathological examination of the whole lesion after surgical excision. Conclusion: Rosai-Dorfman disease confined to the breast is extremely rare, that clinically may mimic breast cancer.

Limited water stress modulates expression of circadian clock genes in Brachypodium distachyon roots.

Organisms have evolved a circadian clock for the precise timing of their biological processes. Studies primarily on model dicots have shown the complexity of the inner timekeeper responsible for maintaining circadian oscillation in plants and have highlighted that circadian regulation is more than relevant to a wide range of biological processes, especially organ development and timing of flowering. Contribution of the circadian clock to overall plant fitness and yield has also long been known. Nevertheless, the organ- and species-specific functions of the circadian clock and its relation to stress adaptation have only recently been identified. Here we report transcriptional changes of core clock genes of the model monocot Brachypodium distachyon under three different light regimes (18:6 light:dark, 24:0 light and 0:24 dark) in response to mild drought stress in roots and green plant parts. Comparative monitoring of core clock gene expression in roots and green plant parts has shown that both phase and amplitude of expression in the roots of Brachypodium plants differ markedly from those in the green plant parts, even under well-watered conditions. Moreover, circadian clock genes responded to water depletion differently in root and shoot. These results suggest an organ-specific form and functions of the circadian clock in Brachypodium roots.

Tumoragnosztikus célzott terápia ­ tropomiozin-receptor-tirozinkináz gátlása a gyakorlatban.

Tumor agnostic therapies target specific genomic alterations regardless of tumor localization and histological subtype. Neurotrophic tropomyosin receptor tyrosine kinase (NTRK) gene fusions are important driver gene targets in both pediatric and adult tumors. The first generation TRK inhibitors provide a rapid, effective, and long-lasting antitumor effect with a favorable side effect profile through selective inhibition of TRK fusion proteins. In the case report, we present a case of a young adult female patient with soft tissue sarcoma, in whom the multiple recurrent lower limb tumor disseminated after 3 years, but the systemic treatments used did not show a meaningful therapeutic response. Molecular diagnostic method confirmed the translocation of a very rare driver oncology target, the neurotrophic tropomyosin receptor tyrosine kinase 3 gene. We used convenient and safe inhibitor of tropomyosin receptor tyrosine kinase larotrectinib therapy with good efficacy and excellent quality of life. Larotrectinib was the first and only systemic therapy to which this metastatic soft tissue tumor responded.

Novel targeted therapeutic option in oncology: tropomyosin receptor tyrosine kinase inhibitors / Új célzott terápiás lehetoség az onkológiában: tropomiozin receptor-tirozin-kináz gátlók.

Összefoglaló. A molekuláris diagnosztikai módszerek folyamatos fejlodésének köszönhetoen egyre több onkogén genetikai eltérést azonosítanak. A neurotrofikus tropomiozin receptor-tirozin-kináz (NTRK-) génfúziók fontos precíziós onkológiai célpontok, melyek mindhárom NTRK-génben elofordulhatnak, onkogén-hajtóeroként viselkednek. A génfúziók különbözo molekuláris diagnosztikai módszerekkel azonosíthatók, melyek közül a legpontosabb, legköltségesebb és legidoigényesebb meghatározást az újgenerációs szekvenálási technika jelenti. A tropomiozin receptor-tirozin-kináz (TRK-) fúziós fehérjék szelektív gátlása személyre szabott onkológiai kezelési lehetoséget jelent a tumor típusától, lokalizációjától és a beteg életkorától függetlenül. Az elso generációs TRK-gátlók gyors, hatékony és tartós daganatellenes hatást biztosítanak kimutatott NTRK-fúzió-pozitív daganatok esetén, alacsony mellékhatásprofil mellett. Az elso generációs TRK-gátlók mellett jelentkezo 'on target' rezisztenciát a második generációs TRK-gátlók oldják fel. Szekvenciális tirozin-kináz-inhibitor-kezeléssel tartós betegségmentes túlélés érheto el. Orv Hetil. 2021; 162(34): 1362-1369. Summary. Due to the continuous development of molecular diagnostic methods, more and more oncogenic genetic abnormalities are being identified. Neurotrophic tropomyosin receptor tyrosine kinase (NTRK) gene fusions are important precision oncology targets that can occur in all three NTRK genes and act as oncogenic drivers. Gene fusions can be identified by a variety of molecular diagnostic technologies, of which next-generation sequencing is the most accurate, costly and time-consuming determination. Selective inhibition of tropomyosin receptor tyrosine kinase (TRK) fusion proteins represents a personalized oncology treatment option regardless of tumour type, localization and patient age. First-generation TRK inhibitors provide rapid, efffective and long-lasting antitumor activity in NTRK fusion-positive tumors with a low side-effect profile. On target resistance to first-generation TRK inhibitors is resolved by second-generation TRK inhibitors. Durable disease-free survival can be achieved with sequential tyrosine kinase inhibitor therapies. Orv Hetil. 2021; 162(34): 1362-1369.

[EGFR protein is a negative prognostic and predictive factor in wild-type RAS colorectal cancer]. / Az EGFR-protein-expresszió negatív prognosztikus és prediktív marker vad RAS típusú vastagbélrákban.

Negative predictive markers of the anti-EGFR antibody therapies are RAS or BRAF mutations, while left sidedness can be considered as a positive predictor. Here we analyzed 97 wild type RAS metastatic colorectal cancers looking for the prognostic and predictive roles of EGFR protein expression. We found that right-sided colorectal cancers are characterized by significantly higher EGFR protein expression as compared to left-sided ones, irrespective of the primary or metastatic tissue analysis. Furthermore, tumors with multiple organ involvement are characterized by significantly higher EGFR protein expression as compared to single organ ones. In the homogenous cetuximab treated cohort (n=90) we have found that lower than the applied EGFR protein expression cut-off was associated with favorable survival. In the multivariate analysis only sidedness proved to be a strong independent predictor, however sidedness is an EGFR-dependent predictor of anti-EGFR therapy.

Using cannabis in oncology: facts and myths / Kannabisz használata az onkológiában: tények és tévhitek

Cannabis belongs to the highly prominent soft drugs; after coffee, tobacco and alcohol, it is considered to be the fourth most consumed psychoactive substance. The two most common cannabinoids are the strictly regulated psychotropic delta-9-tetrahydrocannabinol and the dietary supplement cannabidiol, which is non-psychoactive, only subject to reporting obligation and accessible in Hungary since 2004. In relation to the application of medical cannabis, especially in oncological indications, many misconceptions have arisen. In our review, we summarize the history of cannabis, the mechanism of action, the current evidences for application in oncological indications, the legal regulations, and highlight the potential concerns regarding cannabis administration. Orv Hetil. 2020; 161(25): 1035-1041.

Predictive Markers of First Line Pazopanib Treatment in Kidney Cancer.

Real-world evidence from clinical practices is fundamental for understanding the efficacy and tolerability of medicinal products. Patients with renal cell cancer were studied to gain data not represented by analyses conducted on highly selected patients participating in clinical trials. Our goal was to retrospectively collect data from patients with advanced renal tumours treated with pazopanib (PZ) to investigate the efficacy, frequency of side effects, and searching for predictive markers. Eighty-one patients who had received PZ therapy as first-line treatment were retrospectively evaluated. Overall survival (OS), progression-free survival (PFS) were assessed as endpoints. Median PFS and OS were 11.8 months (95% CI: 8.8-22.4); and 30.2 months (95% CI: 20.3-41.7) respectively. Severe side effects were only encountered in 11 (14%) patients. The presence of liver metastasis shortened the median PFS (5.5 vs. 14.8 months, p = 0.003). Median PFS for patients with or without side effects was 25.6 vs. 7.3 months, respectively (p = 0.0001). Patients younger than 65 years had a median OS of 41.7 months vs. 25.2 months for those over 65 years of age (p = 0.008). According to our results absence of liver metastases, younger age (<65 years) and presence of side effects proved to be independent predictive markers of better PFS and OS.

EGFR Protein Expression in KRAS Wild-Type Metastatic Colorectal Cancer Is Another Negative Predictive Factor of the Cetuximab Therapy.

The selection of colorectal cancer patients for anti-epidermal growth factor receptor (EGFR) antibody therapy is based on the determination of their RAS mutation status-a strongly negative predictive factor-since the protein target, EGFR, is not a reliable predictor of therapeutic response. In this study, we revisited the EGFR protein issue using a cohort of 90 patients with KRAS exon2 wild-type colorectal cancer who have been treated with cetuximab therapy. Twenty-nine of these patients had metastatic tissue available for analysis. The level of EGFR protein expression in the patients was determined by immunohistochemistry and evaluated by H-score (HS) methodology. Progression-free survival (PFS) and overall survival (OS) of the patients were determined according to the EGFR-HS ranges of both the primary and metastatic tissues using Kaplan-Meyer statistics. In the case of primary tumors, EGFR scores lower than HS = 200 were associated with significantly longer OS. In the case of metastatic tissues, all levels lower than the EGFR-HS range chosen were associated with significantly longer OS. These results are explained by the fact that metastatic tissues rarely maintained the expression levels of the primary tumors. On the other hand, high EGFR expression levels in either primary tumors or metastatic tissues were associated with multiple metastatic disease. This suggests a negative prognostic role of EGFR expression. However, in a multivariate analysis, one-sidedness remained a strong independent predictive factor of survival. Previous studies demonstrated that the EGFR expression level depends on sidedness. Therefore, a subgroup analysis of the left- and right-sided cases was performed on both primary and metastatic tissues. In the case of metastic tissues, an analysis confirmed a better OS in low EGFR protein-expressing cases than in high EGFR protein-expressing cases. Collectively, these data suggest that EGFR protein expression is another negative predictive factor of the efficacy of cetuximab therapy of KRAS exon2 wild-type colorectal cancer.

Gene mining in halophytes: functional identification of stress tolerance genes in Lepidium crassifolium.

Extremophile plants are valuable sources of genes conferring tolerance traits, which can be explored to improve stress tolerance of crops. Lepidium crassifolium is a halophytic relative of the model plant Arabidopsis thaliana, and displays tolerance to salt, osmotic and oxidative stresses. We have employed the modified Conditional cDNA Overexpression System to transfer a cDNA library from L. crassifolium to the glycophyte A. thaliana. By screening for salt, osmotic and oxidative stress tolerance through in vitro growth assays and non-destructive chlorophyll fluorescence imaging, 20 Arabidopsis lines were identified with superior performance under restrictive conditions. Several cDNA inserts were cloned and confirmed to be responsible for the enhanced tolerance by analysing independent transgenic lines. Examples include full-length cDNAs encoding proteins with high homologies to GDSL-lipase/esterase or acyl CoA-binding protein or proteins without known function, which could confer tolerance to one or several stress conditions. Our results confirm that random gene transfer from stress tolerant to sensitive plant species is a valuable tool to discover novel genes with potential for biotechnological applications.

Interleukin-1ß (187-207)-induced hyperthermia is inhibited by interleukin-1ß (193-195) in rats.

Interleukin-1ß (IL-1ß) is a pro-inflammatory cytokine, which plays an important role in the immune response and signal transduction both in the periphery and the central nervous system (CNS). Various diseases of the CNS, including neurodegenerative disorders, vascular lesions, meningo-encephalitis or status epilepticus are accompanied by elevated levels of IL-1ß. Different domains within the IL-lß protein are responsible for distinct functions. The IL-lß domain in position 208-240 has pyrogenic properties, while the domain in position 193-195 exerts anti-inflammatory effects. Previous studies provide little evidence about the effect of the domain in position 187-207 on the body temperature. Therefore, the aim of the present study was to investigate the action of IL-1ß (187-207) and its interaction with IL-1ß (193-195) on the body temperature. IL fragments were administered intracerebroventricularly and the body temperature was measured rectally in male Wistar rats. IL-1ß (187-207) induced hyperthermia, while IL-1ß (193-195) did not influence the core temperature considerably. In co-administration, IL-1ß (193-195) completely abolished the IL-1ß (187-207)-induced hyperthermia. The non-steroid anti-inflammatory drug metamizole also reversed completely the action of IL-1ß (187-207). Our results provide evidence that the IL-lß domain in position 187-207 has hyperthermic effect. This effect is mediated through prostaglandin E2 stimulation and other mechanisms may also be involved in the action of IL-1ß (187-207). It also suggests that IL-lß domain in position 187-207 and IL-1ß (193-195) fragment may serve as novel target for treatment of disorders accompanied with hyperthermia.

[Our experience with targeted therapy in glioblastoma multiforme]. / Glioblastoma multiforméban szenvedo betegek célzott terápiás kezelésével szerzett tapasztalataink.

Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor in adults. The current standard therapy includes surgical resection or biopsy, followed by a combination of radiation and chemotherapy with temozolomide. After progression or recurrence there is only one recommended effective therapy, bevacizumab. Bevacizumab is a monoclonal VEGF inhibitor antibody, inhibiting the angiogenesis in highly vascularized tumors. Resent studies focused on adjuvant treatment with targeted therapy in newly diagnosed tumors. Our purpose is to evaluate the data from patients treated in our department investigate the clinical response and side effects profile and to compare these data with the international results. The applied protocol was well tolerated and side effects corresponded to the already reported ones. The median PFS and survival data correlate with those in the literature. The AVAglio study demonstrated that the addition of bevacizumab to the adjuvant therapy increased PFS significantly.

The role of NPY in the mediation of orexin-induced hypothermia.

The mediation of orexin-A-induced hypothermia was investigated. Different doses of orexin-A (140-560 pmol) were administered intracerebroventricularly (i.c.v.) to adult male rats, and the colon temperature was used as an index of the thermoregulatory action. Orexin-A decreased both the basal colon temperature and the lipopolysaccharide-induced fever and exhibited a bell-shaped dose-response curve. I.c.v. pretreatment with neuropeptide Y (NPY) antiserum 24 h before orexin administration significantly decreased the hypothermic effect of orexin-A. These data strengthen the hypothesis that this appetite-regulating peptide might also play a role in thermoregulation, and its hypothermic effect seems to be mediated at least partially by NPY.