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Purpose: Appendectomy is the standard treatment of acute appendicitis. However, recent advancements have introduced medical treatment as a potential alternative. Within this context, it's important to recognize the rare occurrence of appendiceal tumors, often incidentally discovered during histopathological examination following appendectomy. Consequently, there's a concern about the possibility of overlooking appendiceal neoplasms, particularly in cases where conservative treatment for acute appendicitis is considered., Methods: The files of patients who underwent surgery for acute appendicitis between January 2015 and December 2023 and were diagnosed with neoplasia in their pathology reports were retrospectively registered. Demographic characteristics of the patients, laboratory and imaging features, details of the surgery performed, preoperative and intraoperative suspicion of neoplasm and data from pathology reports were collected and analyzed., Results: A total of 6446 patients were operated for acute appendicitis. Neoplasia was detected in the histopathological examination of 93 patients (1.44%). Acute appendicitis was diagnosed in 51.6% of the patients by computed tomography. Neoplasm suspicion was present in 9.7% of patients in preoperative imaging methods and in 6.5% of patients intraoperatively. Only appendectomy was performed in 94.5% of patients. The most common appendiceal neoplasm is neuroendocrine tumors (40.9%), followed by appendiceal mucinous neoplasm (29%), sessile serrated adenoma (15%), and adenocarcinoma (6.5%)., Conclusion: Although appendiceal neoplasms are relatively rare in proportion, they represent a significant numerical value due to the density of cases. Therefore, this information should be taken into consideration when evaluating treatment options for acute appendicitis., Competing Interests: Declarations. Consent to participate: Informed consent was obtained from all individual participants of the study. Competing interest: The authors declare no competing interests. Human and animal rights: All procedures performed in this study involving human participants were in accordance with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This article does not contain any study with animals performed by any of the authors., (© 2024. The Author(s), under exclusive licence to Royal Academy of Medicine in Ireland.)

Objective: This study aimed to investigate the effects of upper extremity home exercises on grip strength, range of motion, activity performance, and functionality in individuals with systemic sclerosis and to compare with patient education., Methods: A total of 46 individuals with systemic sclerosis (55.52±11.54 years) were included. Individuals were randomly assigned into intervention (n=23) and control (n=23) groups. Dynamometer, goniometer, Canadian Occupational Performance Measurement, Disabilities of the Arm, Shoulder, and Hand, Score for Assessment and Quantification of Chronic Rheumatic Affections of the Hands, and Duruoz Hand Index were used for evaluation., Results: Post-treatment, in terms of delta (Δ) values, hand grip and pinch strengths (p: 0.000-0.016), active (p: 0.000-0.032) and passive (p: 0.000-0.043) total range of motions, Canadian Occupational Performance Measurement performance and satisfaction, Disabilities of the Arm, Shoulder, Score for Assessment and Quantification of Chronic Rheumatic Affections of the Hands, and Duruoz Hand Index (p: 0.000) were in favor of the intervention group., Conclusion: Upper extremity home exercises increase grip strength, range of motion, activity performance, and functionality in patients with systemic sclerosis. We recommend that rehabilitation programs include not only hand exercises but also upper extremity exercises.

The aim of the study was to examine the relationship between pelvic floor functions and sexual functions in women with fibromyalgia. The study included 204 women with fibromyalgia, mean aged 43.43 ± 8.61 years. All patients who met the inclusion criteria and applied to the rheumatology outpatient clinic were included in the study. The study was conducted between September 2020 and June 2022. The Female Sexual Function Scale (FSFI) was used to evaluate sexual function, Pelvic Floor Distress Scale-20 (PFDI-20), Pelvic Floor Impact Questionnaire (PFIQ-7) and Pelvic Organ Prolapse/Incontinence Sexual Function Assessment (PSIQ-12) were used to evaluate pelvic floor problems. The relationship between sexual dysfunction and other parameters was analyzed using Spearman correlation analysis. There was a weak negative correlation between many sub-parameters of FSFI and scores of PFDI-20, PFIQ-7, PSIQ-12 (r:-0.165--0.377 p: 0.02-0.00). According to the results of this study, sexual dysfunction was negatively affected by pelvic floor dysfunction and symptoms related to bladder, bowel, and pelvic organs in women with fibromyalgia. These results may suggest that sexual function and pelvic floor problems in women with fibromyalgia should be considered together and an approach should be planned for such problems in treatment programs.

EGFR is one of the important mediators of the signaling cascade that determines key roles in various biological processes such as growth, differentiation, metabolism and apoptosis in the cell in response to external and internal stimuli. In recent years, it has been proven that although this enzyme activity is tightly regulated in normal cells, if the enzyme activity cannot be controlled, it can lead to malignancy. EGFR is also considered a prominent macromolecule in targeted cancer chemotherapy. For this purpose, a comprehensive modeling studies were conducted against EGFR protein and novel molecules containing 5-[(1 H -1,2,4-triazol-1-yl)methyl]-3 H -1,2,4-triazole-3-thione structure were suggested to be synthesized. Among the synthesized molecules, compounds 7c , 8c , 8f and 8g were determined to have significant IC 50 values. Compound 8g was found to have the IC 50 value closest to the very well-known EGFR inhibitor Gefitinib with its noncompetitive inhibition form. K i value of compound 8g was calculated as 0.00232 µM.Communicated by Ramaswamy H. Sarma.

Background The coronavirus disease 2019 (COVID-19) epidemic was recognized as a pandemic by the World Health Organization on March 2020. There have been significant changes in our lives due to the measures used to prevent the spread of the COVID-19 pandemic. Dementia patients are one of the most vulnerable groups who have difficulties in adapting to this situation. Our study aimed to compare the admission rate to the hospital and dementia characteristics of dementia patients in the COVID-19 pandemic and pre-pandemic periods. Methods Dementia patients admitted to the neurology outpatient clinic during the pandemic and pre-pandemic periods were included in the study. In these two periods, age, gender, dementia type, stage, age of onset, mini-mental state examination, reason for admission, vitamin B12, vitamin D, folic acid levels, brain imaging, electroencephalogram results were analysed retrospectively. Dementia characteristics and vitamin levels were compared. Results Two hundred and two dementia patients were included in the study. When the reasons for admission to the hospital were examined, the number of applications with the complaint of forgetfulness was highest in the pre-COVID period (53.1%); this rate was 37.8% in the COVID period. Also, 9.5% of patients were admitted for a drug prescription or medication report during the COVID period, while this rate was 1.6% in the pre-COVID period. Brain imaging was performed on 91 patients in the pre-COVID period, while 42 patients underwent imaging in the COVID period. Conclusions Although this study was performed with a limited population, it indicates that the COVID-19 pandemic indirectly affects the clinical conditions of people living with dementia., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Morkavuk et al.)

Background: Over the past 15 years, 300 out of 6000 breeds of all farm animal species identified by the Food and Agriculture Organization of the United Nations (FAO) have gone extinct. Among cattle, many Podolian breeds are seriously endangered in various European areas. Podolian cattle include a group of very ancient European breeds, phenotypically close to the aurochs ancestors (Bos primigenius). The aim of the present study was to assess the genetic diversity of Podolian breeds and to reconstruct their origin., Methodology: The mitochondrial DNA (mtDNA) control-regions of 18 Podolian breeds have been phylogenetically assessed. Nine non-Podolian breeds have been also included for comparison., Conclusion: The overall analysis clearly highlights some peculiarities in the mtDNA gene pool of some Podolian breeds. In particular, a principal component analysis point to a genetic proximity between five breeds (Chianina, Marchigiana, Maremmana, Podolica Italiana and Romagnola) reared in Central Italy and the Turkish Grey. We here propose the suggestive hypothesis of a dual ancestral contribution to the present gene pool of Podolian breeds, one deriving from Eastern European cattle; the other arising from the arrival of Middle Eastern cattle into Central Italy through a different route, perhaps by sea, ferried by Etruscan boats. The historical migration of Podolian cattle from North Eastern Europe towards Italy has not cancelled the mtDNA footprints of this previous ancient migration.

Although FGF5 mRNA was previously found expressed in some melanoma cell lines in contrast to normal human melanocytes, neither its contribution to melanoma growth nor its expression in melanoma tissue has been investigated. Here we demonstrate that ectopic overexpression of FGF5 in human melanoma cells with low endogenous FGF5 expression increased clonogenicity and invasion but not short-term growth in vitro . Silencing of FGF5 in melanoma cells with high endogenous FGF5 expression had the opposite effect on clonogenicity. FGF overexpression led to increased signaling along the MAPK and NFAT axis but had no effect on STAT3 signaling. In an in vivo experiment in immunocompromised mice, human melanoma xenografts overexpressing FGF5 showed enhanced tumor growth, a higher Ki-67 proliferation index, decreased apoptosis and enhanced angiogenesis. Immunohistochemistry performed on a tissue microarray demonstrated FGF5 protein expression in more than 50% of samples of melanoma and benign nevi. These data suggest that FGF5 has oncogenic potential in melanoma cells and contributes to melanoma growth in a subset of patients. This highlights the importance of further evaluating FGF5 as potential biomarker and therapy target in melanoma., Competing Interests: CONFLICTS OF INTEREST The authors declare no conflicts of interest.

Synovial fibroblasts are key cells orchestrating the inflammatory response in arthritis. Here we demonstrate that loss of miR-146a, a key epigenetic regulator of the innate immune response, leads to increased joint destruction in a TNF-driven model of arthritis by specifically regulating the behavior of synovial fibroblasts. Absence of miR-146a in synovial fibroblasts display a highly deregulated gene expression pattern and enhanced proliferation in vitro and in vivo. Deficiency of miR-146a induces deregulation of tumor necrosis factor (TNF) receptor associated factor 6 (TRAF6) in synovial fibroblasts, leading to increased proliferation. In addition, loss of miR-146a shifts the metabolic state of fibroblasts towards glycolysis and augments the ability of synovial fibroblasts to support the generation of osteoclasts by controlling the balance of osteoclastogenic regulatory factors receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG). Bone marrow transplantation experiments confirmed the importance of miR-146a in the radioresistant mesenchymal compartment for the control of arthritis severity, in particular for inflammatory joint destruction. This study therefore identifies microRNA-146a as an important local epigenetic regulator of the inflammatory response in arthritis. It is a central element of an anti-inflammatory feedback loop in resident synovial fibroblasts, who are orchestrating the inflammatory response in chronic arthritis. MiR-146a restricts their activation, thereby preventing excessive tissue damage during arthritis., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Acyclovir is a synthetic guanosine analog, which is a potent and highly selective inhibitor of the DNA polymerases of several herpes viruses. Acyclovir is known as a relatively safe drug with few significant adverse effects, of which nephrotoxicity seems to be the most dreaded one. On the other hand, inflammation and phlebitis at the injection site have been reported to be the most frequent side effects of intravenous acyclovir administration. Although exceptionally rare, there have been case reports of bullous eruption occurring after intravenous acyclovir therapy, a similar of which we have also observed. Here, we present a case of localized bullous eruption and phlebitis associated with intravenous acyclovir treatment in a patient with metastatic breast cancer. Our case distinctively demonstrated two consequential juxtaposing vesiculobullous lesions and phlebitis manifesting as erythema along the course of a vein after intravenous acyclovir injection. We emphasize this hardly known side effect and importance of early recognition and appropriate management of unpredictable side effects of widely used medications.

Multiple sclerosis (MS) is the most common autoimmune disease affecting the central nervous system. It is characterized by auto-reactive T cells that induce demyelination and neuronal degradation. Treatment options are still limited and several MS medications need to be administered by parenteral application but are modestly effective. Oral active drugs such as fingolimod have been weighed down by safety concerns. Consequently, there is a demand for novel, especially orally active therapeutics. Nature offers an abundance of compounds for drug discovery. Recently, the circular plant peptide kalata B1 was shown to silence T-cell proliferation in vitro in an IL-2-dependent mechanism. Owing to this promising effect, we aimed to determine in vivo activity of the cyclotide [T20K]kalata B1 using the MS mouse model experimental autoimmune encephalomyelitis (EAE). Treatment of mice with the cyclotide resulted in a significant delay and diminished symptoms of EAE by oral administration. Cyclotide application substantially impeded disease progression and did not exhibit adverse effects. Inhibition of lymphocyte proliferation and the reduction of proinflammatory cytokines, in particular IL-2, distinguish the cyclotide from other marketed drugs. Considering their stable structural topology and oral activity, cyclotides are candidates as peptide therapeutics for pharmaceutical drug development for treatment of T-cell-mediated disorders.

Idiopathic pulmonary fibrosis (IPF) is a life-threatening disease with limited treatment options. Additionally, the lack of a complete understanding of underlying immunological mechanisms underscores the importance of discovering novel options for therapeutic intervention. Since the PI3K/PTEN pathway in myeloid cells influences their effector functions, we wanted to elucidate how sustained PI3K activity induced by cell-type specific genetic deficiency of its antagonist PTEN modulates IPF, in a murine model of bleomycin-induced pulmonary fibrosis (BIPF). We found that myeloid PTEN deficient mice (PTEN(MyKO)), after induction of BIPF, exhibit increased TGF-β1 activation, mRNA expression of pro-collagens and lysyl oxidase as well as augmented collagen deposition compared to wild-type littermates, leading to enhanced morbidity and decreased survival. Analysis of alveolar lavage and lung cell composition revealed that PTEN(MyKO) mice exhibit reduced numbers of macrophages and T-cells in response to bleomycin, indicating an impaired recruitment function. Interestingly, we found dysregulated macrophage polarization as well as elevated expression and release of the pro-fibrotic cytokines IL-6 and TNF-α in PTEN(MyKO) mice during BIPF. This might point to an uncontrolled wound healing response in which the inflammatory as well as tissue repair mechanisms proceed in parallel, thereby preventing resolution and at the same time promoting extensive fibrosis.

The PI3K signaling cascade in APCs has been recognized as an essential pathway to initiate, maintain, and resolve immune responses. In this study, we demonstrate that a cell type-specific loss of the PI3K antagonist phosphatase and tensin homolog (PTEN) in myeloid cells renders APCs toward a regulatory phenotype. APCs deficient for PTEN exhibit reduced activation of p38 MAPK and reduced expression of T cell-polarizing cytokines. Furthermore, PTEN deficiency leads to upregulation of markers for alternative activation, such as Arginase 1, with concomitant downregulation of inducible NO synthase in APCs in vitro and in vivo. As a result, T cell polarization was dysfunctional in PTEN(-/-) APCs, in particular affecting the Th17 cell subset. Intriguingly, mice with cell type-specific deletions of PTEN-targeting APCs were protected from experimental autoimmune encephalomyelitis, which was accompanied by a pronounced reduction of IL-17- and IL-22-producing autoreactive T cells and reduced CNS influx of classically activated monocytes/macrophages. These observations support the notion that activation of the PI3K signaling cascade promotes regulatory APC properties and suppresses pathogenic T cell polarization, thereby reducing the clinical symptoms and pathology of experimental autoimmune encephalomyelitis., (Copyright © 2015 by The American Association of Immunologists, Inc.)

Introduction: Autoreactive T cells are a central element in many systemic autoimmune diseases. The generation of these pathogenic T cells is instructed by antigen-presenting cells (APCs). However, signaling pathways in APCs that drive autoimmune diseases, such as rheumatoid arthritis, are not understood., Methods: We measured phenotypic maturation, cytokine production and induction of T cell proliferation of APCs derived from wt mice and mice with a myeloid-specific deletion of PTEN (myeloid PTEN(-/-)) in vitro and in vivo. We induced collagen-induced arthritis (CIA) and K/BxN serum transfer arthritis in wt and myeloid-specific PTEN(-/-) mice. We measured the cellular composition of lymph nodes by flow cytometry and cytokines in serum and after ex vivo stimulation of T cells., Results: We show that myeloid-specific PTEN(-/-) mice are almost protected from CIA. Myeloid-specific deletion of PTEN leads to a significant reduction of cytokine expression pivotal for the induction of systemic autoimmunity such as interleukin (IL)-23 and IL-6, leading to a significant reduction of a Th17 type of immune response characterized by reduced production of IL-17 and IL-22. In contrast, myeloid-specific PTEN deficiency did not affect K/BxN serum transfer arthritis, which is independent of the adaptive immune system and solely depends on innate effector functions., Conclusions: These data demonstrate that the presence of PTEN in myeloid cells is required for the development of CIA. Deletion of PTEN in myeloid cells inhibits the development of autoimmune arthritis by preventing the generation of a pathogenic Th17 type of immune response.

Dendritic cell (DC)-mediated inflammation induced via TLRs is promoted by MAPK-activated protein kinase (MK)-2, a substrate of p38 MAPK. In this study we show an opposing role of MK2, by which it consolidates immune regulatory functions in DCs through modulation of p38, ERK1/2-MAPK, and STAT3 signaling. During primary TLR/p38 signaling, MK2 mediates the inhibition of p38 activation and positively cross-regulates ERK1/2 activity, leading to a reduction of IL-12 and IL-1α/β secretion. Consequently, MK2 impairs secondary autocrine IL-1α signaling in DCs, which further decreases the IL-1α/p38 but increases the anti-inflammatory IL-10/STAT3 signaling route. Therefore, the blockade of MK2 activity enables human and murine DCs to strengthen proinflammatory effector mechanisms by promoting IL-1α-mediated Th1 effector functions in vitro. Furthermore, MK2-deficient DCs trigger Th1 differentiation and Ag-specific cytotoxicity in vivo. Finally, wild-type mice immunized with LPS in the presence of an MK2 inhibitor strongly accumulate Th1 cells in their lymph nodes. These observations correlate with a severe clinical course in DC-specific MK2 knockout mice compared with wild-type littermates upon induction of experimental autoimmune encephalitis. Our data suggest that MK2 exerts a profound anti-inflammatory effect that prevents DCs from prolonging excessive Th1 effector T cell functions and autoimmunity., (Copyright © 2015 by The American Association of Immunologists, Inc.)

Background & Aims: Intrahepatic granuloma formation and fibrosis characterize the pathological features of Schistosoma mansoni infection. Based on previously observed substantial anti-fibrotic effects of 24-nor-ursodeoxycholic acid (norUDCA) in Abcb4/Mdr2(-/-) mice with cholestatic liver injury and biliary fibrosis, we hypothesized that norUDCA improves inflammation-driven liver fibrosis in S. mansoni infection., Methods: Adult NMRI mice were infected with 50 S. mansoni cercariae and after 12 weeks received either norUDCA- or ursodeoxycholic acid (UDCA)-enriched diet (0.5% wt/wt) for 4 weeks. Bile acid effects on liver histology, serum biochemistry, key regulatory cytokines, hepatic hydroxyproline content as well as granuloma formation were compared to naive mice and infected controls. In addition, effects of norUDCA on primary T-cell activation/proliferation and maturation of the antigen-presenting-cells (dendritic cells, macrophages) were determined in vitro., Results: UDCA as well as norUDCA attenuated the inflammatory response in livers of S. mansoni infected mice, but exclusively norUDCA changed cellular composition and reduced size of hepatic granulomas as well as TH2-mediated hepatic fibrosis in vivo. Moreover, norUDCA affected surface expression level of major histocompatibility complex (MHC) class II of macrophages and dendritic cells as well as activation/proliferation of T-lymphocytes in vitro, whereas UDCA had no effect., Conclusions: This study demonstrates pronounced anti-inflammatory and anti-fibrotic effects of norUDCA compared to UDCA in S. mansoni induced liver injury, and indicates that norUDCA directly represses antigen presentation of antigen presenting cells and subsequent T-cell activation in vitro. Therefore, norUDCA represents a promising drug for the treatment of this important cause of liver fibrosis., (Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Objective: Local bone destruction in rheumatic diseases, which often leads to disability and severely reduced quality of life, is almost exclusively mediated by osteoclasts. Therefore, it is important to understand pathways regulating the generation of osteoclasts. Here, we analysed the impact of the Phosphoinositide-3-Kinase (PI3K)/Phosphatase and tensin homolog (PTEN) axis on osteoclast generation and bone biology under basal and inflammatory conditions., Methods: We analysed osteoclastogenesis of wildtype (wt) and PTEN(-/-) cells in vitro and in vivo, pit resorption and qPCR of osteoclasts in vitro. Mice with a myeloid cell-specific deletion of PTEN and wt littermate mice were investigated by bone histomorphometry and clinical and histological assessment in the human tumour necrosis factor (TNF)-transgenic (hTNFtg) arthritis model., Results: We show that myeloid-specific PTEN(-/-) mice display increased osteoclastogenesis in vitro and in vivo compared to wt mice. Loss of PTEN did not affect the generation or survival of osteoclast precursor cells. However, PTEN deficiency greatly enhanced receptor activator of nuclear factor κ-B ligand (RANKL)-induced expression of the master transcription factor of osteoclastogenesis, nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), resulting in markedly increased terminal differentiation of osteoclasts in vitro. We also observed increased osteoclastogenesis under inflammatory conditions in the hTNFtg mouse model of arthritis, where hTNFtg/myeloid-specific PTEN(-/-) mice displayed enhanced local bone destruction as well as osteoclast formation in the inflamed joints. The extent of synovial inflammation, however, as well as recruitment of osteoclast precursor cells was not different between wt and myeloid-specific PTEN(-/-) mice., Conclusions: These data demonstrate that loss of PTEN and, therefore, sustained PI3-Kinase signalling in myeloid cells especially, elevates the osteoclastogenic potential of myeloid cells, leading to enhanced inflammatory local bone destruction. Therefore, although our study allows no direct translational conclusion since we used a conditional knockout approach, the therapeutic targeting of the PI3-Kinase pathway may be of benefit in preventing structural joint damage., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

The activation of innate immune cells triggers numerous intracellular signaling pathways, which require tight control to mount an adequate immune response. The PI3K signaling pathway is intricately involved in innate immunity, and its activation dampens the expression and release of proinflammatory cytokines in myeloid cells. These signaling processes are strictly regulated by the PI3K antagonist, the lipid phosphatase, PTEN, a known tumor suppressor. Importantly, PTEN is responsible for the elevated production of cytokines such as IL-6 in response to TLR agonists, and deletion of PTEN results in diminished inflammatory responses. However, the mechanisms by which PI3K negatively regulates TLR signaling are only partially resolved. We observed that Arginase I expression and secretion were markedly induced by PTEN deletion, suggesting PTEN(-/-) macrophages were alternatively activated. This was mediated by increased expression and activation of the transcription factors C/EBPβ and STAT3. Genetic and pharmacologic experimental approaches in vitro, as well as in vivo autoimmunity models, provide convincing evidence that PI3K/PTEN-regulated extracellular Arginase I acts as a paracrine regulator of inflammation and immunity., (Copyright © 2014 by The American Association of Immunologists, Inc.)

Sepsis still remains a major cause for morbidity and mortality in patients. The molecular mechanisms underlying the disease are still enigmatic. A great number of therapeutic approaches have failed and treatment strategies are limited to date. Among those few admitted for clinical intervention, intensive insulin treatment has proven to be effective in the reduction of disease related complications in critically ill patients. Insulin effectively reduces glucose levels and thereby contributes to protection. On the other hand insulin is a potent signaling pathway activator. One of those is the PI3K signaling axis. Activation of PI3K is known to limit pro-inflammatory gene expression. Here we can show that in a mouse model of insulin hypersensitivity induced by the deletion of the PI3K antagonist PTEN, specifically in hepatic tissue, significant protection is conferred in murine models of lethal endotoxemia and sepsis. Acute inflammatory responses are diminished, glucose metabolism normalized and vascular activation is reduced. Furthermore we investigated the hepatic gene expression profile of relevant anti-inflammatory genes in PTEN deficient mice and found marked upregulation of PPARγ and HO-1. We conclude from our data that insulin hypersensitivity via sustained activation of the PI3K signaling pathway exerts protective effects in acute inflammatory processes.

The present study investigates extracts of Neuolaena lobata, an anti-protozoan ethnomedicinal plant of the Maya, regarding its anti-neoplastic properties. Firstly, extracts of increasing polarity were tested in HL-60 cells analyzing inhibition of cell proliferation and apoptosis induction. Secondly, the most active extract was further tested in anaplastic large cell lymphoma (ALCL) cell lines of human and mouse origin. The dichloromethane extract inhibited proliferation of HL-60, human and mouse ALCL cells with an IC50 of ~2.5, 3.7 and 2.4 µg/ml, respectively and arrested cells in the G2/M phase. The extract induced the checkpoint kinases Chk1 and Chk2 and perturbed the orchestrated expression of the Cdc25 family of cell cycle phosphatases which was paralleled by the activation of p53, p21 and downregulation of c-Myc. Importantly, the expression of NPM/ALK and its effector JunB were drastically decreased, which correlated with the activation of caspase 3. Subsequently also platelet derived growth factor receptor β was downregulated, which was recently shown to be transcriptionally controlled by JunB synergizing with ALK in ALCL development. We show that a traditional healing plant extract downregulates various oncogenes, induces tumor suppressors, inhibits cell proliferation and triggers apoptosis of malignant cells. The discovery of the 'Active Principle(s)' is warranted.