Source:European Journal of Cancer, Volume 96
Author(s): Hope S. Rugo, Javier Cortes
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Cancer Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174
Σάββατο 12 Μαΐου 2018
The new world of biosimilars in oncology: Translation of data to the clinic
Source:European Journal of Cancer, Volume 96
Author(s): Hope S. Rugo, Javier Cortes
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Exceptional response to olaparib in BRCA2-altered urothelial carcinoma after PD-L1 inhibitor and chemotherapy failure
Source:European Journal of Cancer, Volume 96
Author(s): Andrea Necchi, Daniele Raggi, Patrizia Giannatempo, Alessandra Alessi, Gianluca Serafini, Maurizio Colecchia, Siraj M. Ali, Jon H. Chung
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Letter comments on EJC published paper: ‘No overdiagnosis in the Norwegian Breast Cancer Screening Program estimated by combining record linkage and questionnaire information in the Norwegian Women and Cancer study’
Source:European Journal of Cancer
Author(s): Per Henrik Zahl
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Re: No overdiagnosis in the Norwegian Breast Cancer Screening Program estimated by combining record linkage and questionnaire information in the Norwegian Women and Cancer Study
Source:European Journal of Cancer
Author(s): Eiliv Lund, Aurelie Nakamura, Jean-Christophe Thalabard
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Combined high dose rate brachytherapy and external beam radiotherapy for clinically localised prostate cancer
To report the clinical outcomes and treatment-related toxicities after combined high-dose-rate (HDR) brachytherapy (BRT) with external beam radiotherapy (EBRT) for patients with clinically localised high-risk prostate cancer.
https://ift.tt/2KSAU2F
An unusual finding in a desmoid-type fibromatosis of the pancreas: a case report and review of the literature
Desmoid-type fibromatoses are rare benign and fibrous tumors that account for approximately 0.03% of total neoplasms. Within this category of neoplasms, pancreatic desmoid-type fibromatosis is an extremely rar...
https://ift.tt/2KV7pxf
Resveratrol analogue, (E)- N -(2-(4-methoxystyryl) phenyl) furan-2-carboxamide induces G 2 /M cell cycle arrest through the activation of p53–p21 CIP1/WAF1 in human colorectal HCT116 cells
Abstract
Resveratrol, a naturally occurring polyphenolic antioxidant, is a potential chemoprophylactic agent for various cancers, including colorectal cancer. Although emerging evidence continually suggests that a number of resveratrol derivatives may be better cancer chemopreventive candidates than resveratrol, studies on the mechanism of action of these derivatives are limited. This is the first study which investigates the mechanism underlying the cytotoxic effect of a synthesized resveratrol analogue, (E)-N-(2-(4-methoxystyryl) phenyl) furan-2-carboxamide (CS) on colorectal cancer. Previously, our group reported a series of synthesized resveratrol analogues, which showed cytotoxicity against a panel of cancer cell lines, in particular on colon cancer cells. In this study, we further discovered that CS also exerts a potent suppressive effect on HCT116 colorectal cancer cells. In contrast, normal colon cells (CCD-112 Con) were not sensitive to CS up to 72 h post treatment. CS caused cytotoxicity in HCT116 cells through several apoptotic events including activation of the Fas death receptor, FADD, caspase 8, caspase 3, caspase 9, and cleaved PARP, which occurred alongside cell cycle arrest from the up-regulation of p53 and p21. The results show that CS causes apoptosis via the activation of an extrinsic pathway leading to caspase activation and cell cycle arrest from activated p53. These findings suggest that CS may be a potential candidate for development as an anti-tumor agent in the future.
https://ift.tt/2Igbqe3
Physical interaction of STAT1 isoforms with TGF-β receptors leads to functional crosstalk between two signaling pathways in epithelial ovarian cancer
The signal transducer and activator of transcription (STAT) and transforming growth factor-β (TGF-β) signaling pathways play important roles in epithelial ovarian cancer (EOC). However, the mechanism of crosst...
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PSMA-PET based radiotherapy: a review of initial experiences, survey on current practice and future perspectives
68Gallium prostate specific membrane antigen (PSMA) ligand positron emission tomography (PET) is an increasingly used imaging modality in prostate cancer, especially in cases of tumor recurrence after curative i....
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PSMA-PET based radiotherapy: a review of initial experiences, survey on current practice and future perspectives
68Gallium prostate specific membrane antigen (PSMA) ligand positron emission tomography (PET) is an increasingly used imaging modality in prostate cancer, especially in cases of tumor recurrence after curative i....
https://ift.tt/2wGpGv0
Glycolysis inhibition as a strategy for hepatocellular carcinoma treatment?
| Related Articles |
Glycolysis inhibition as a strategy for hepatocellular carcinoma treatment?
Curr Cancer Drug Targets. 2018 Apr 30;:
Authors: Alves A, Mamede AC, Alves M, Oliveira PF, Rocha SM, Botelho F, Maia CJ
Abstract
Hepatocellular carcinoma (HCC) is the most frequently detected primary malignant liver tumor, representing a worldwide public health problem due to its high morbidity and mortality rates. The HCC is commonly detected in advanced stage, precluding the use of treatments with curative intent. For this reason, it is crucial to find effective therapies for HCC. Cancer cells have a high dependence of glycolysis for ATP production, especially under hypoxic environment. Such dependence provides a reliable possible strategy to specifically target cancer cells based on the inhibition of glycolysis. HCC, such as other cancer types, presents a clinical well-known upregulation of several glycolytic key enzymes and proteins, including glucose transporters particularly glucose transporter 1 (GLUT1). Such enzymes and proteins constitute potential targets for therapy. Indeed, for some of these targets, several inhibitors were already reported, such as 2-Deoxyglucose, Imatinib or Flavonoids. Although the inhibition of glycolysis presents a great potential for an anticancer therapy, the development of glycolytic inhibitors as a new class of anticancer agents needs to be more explored. Herein, we propose to summarize, discuss and present an overview on the different approaches to inhibit the glycolytic metabolism in cancer cells, which may be very effective in the treatment of HCC.
PMID: 29749314 [PubMed - as supplied by publisher]
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Met is involved in TIGAR-regulated metastasis of non-small-cell lung cancer
Abstract
TIGAR is a p53 target gene that is known to protect cells from ROS-induced apoptosis by promoting the pentose phosphate pathway. The role of TIGAR in tumor cell invasion and metastasis remains elusive. Here we found that downregulation of TIGAR reduced the invasion and metastasis of NSCLC cells in vitro and in vivo. Immunohistochemical analysis of 72 NSCLC patients showed that TIGAR and Met protein expression was positively correlated with late stages of lung cancer. Besides, patients with high co-expression of TIGAR and Met presented a significantly worse survival. In addition, we found that Met signaling pathway is involved in TIGAR-induced invasion and metastasis. Our study indicates that TIGAR/Met pathway may be a novel target for NSCLC therapy. It is necessary to evaluate the expression of TIGAR before Met inhibitors are used for NSCLC treatment.
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Long noncoding RNA DANCR, working as a competitive endogenous RNA, promotes ROCK1-mediated proliferation and metastasis via decoying of miR-335-5p and miR-1972 in osteosarcoma
Abstract
Background
Accumulating evidences indicate that non-coding RNAs (ncRNAs) including long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) acting as crucial regulators in osteosarcoma (OS). Previously, we reported that Rho associated coiled-coil containing protein kinase 1 (ROCK1), a metastatic-related gene was negatively regulated by microRNA-335-5p (miR-335-5p) and work as an oncogene in osteosarcoma. Whether any long non-coding RNAs participate in the upstream of miR-335-5p/ROCK1 axial remains unclear.
Methods
Expression of differentiation antagonizing non-protein coding RNA (DANCR) and miR-335-5p/miR-1972 in osteosarcoma tissues were determined by a qRT-PCR assay and an ISH assay. Osteosarcoma cells' proliferation and migration/invasion ability changes were measured by a CCK-8/EDU assay and a transwell assay respectively. ROCK1 expression changes were checked by a qRT-PCR assay and a western blot assay. Targeted binding effects between miR-335-5p/miR-1972 and ROCK1 or DANCR were verified by a dual luciferase reporter assay and a RIP assay. In vivo experiments including a nude formation assay as well as a CT scan were applied to detect tumor growth and metastasis changes in animal level.
Results
In the present study, an elevated DNACR was found in osteosarcoma tissue specimens and in osteosarcoma cell lines, and the elevated DNACR was closely correlated with poor prognosis in clinical patients. Functional experiments illustrated that a depression of DANCR suppressed ROCK1-mediated proliferation and metastasis in osteosarcoma cells. The results of western blot assays and qRT-PCR assays revealed that DANCR regulated ROCK1 via crosstalk with miR-335-5p and miR-1972. Further cellular behavioral experiments demonstrated that DNACR promoted ROCK1-meidated proliferation and metastasis through decoying both miR-335-5p and miR-1972. Finally, the outcomes of in vivo animal models showed that DANCR promoted tumor growth and lung metastasis of osteosarcoma.
Conclusions
LncRNA DANCR work as an oncogene and promoted ROCK1-mediated proliferation and metastasis through acting as a competing endogenous RNA (ceRNA) in osteosarcoma.
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Met is involved in TIGAR-regulated metastasis of non-small-cell lung cancer
Abstract
TIGAR is a p53 target gene that is known to protect cells from ROS-induced apoptosis by promoting the pentose phosphate pathway. The role of TIGAR in tumor cell invasion and metastasis remains elusive. Here we found that downregulation of TIGAR reduced the invasion and metastasis of NSCLC cells in vitro and in vivo. Immunohistochemical analysis of 72 NSCLC patients showed that TIGAR and Met protein expression was positively correlated with late stages of lung cancer. Besides, patients with high co-expression of TIGAR and Met presented a significantly worse survival. In addition, we found that Met signaling pathway is involved in TIGAR-induced invasion and metastasis. Our study indicates that TIGAR/Met pathway may be a novel target for NSCLC therapy. It is necessary to evaluate the expression of TIGAR before Met inhibitors are used for NSCLC treatment.
https://ift.tt/2KWJuxF
Long noncoding RNA DANCR, working as a competitive endogenous RNA, promotes ROCK1-mediated proliferation and metastasis via decoying of miR-335-5p and miR-1972 in osteosarcoma
Abstract
Background
Accumulating evidences indicate that non-coding RNAs (ncRNAs) including long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) acting as crucial regulators in osteosarcoma (OS). Previously, we reported that Rho associated coiled-coil containing protein kinase 1 (ROCK1), a metastatic-related gene was negatively regulated by microRNA-335-5p (miR-335-5p) and work as an oncogene in osteosarcoma. Whether any long non-coding RNAs participate in the upstream of miR-335-5p/ROCK1 axial remains unclear.
Methods
Expression of differentiation antagonizing non-protein coding RNA (DANCR) and miR-335-5p/miR-1972 in osteosarcoma tissues were determined by a qRT-PCR assay and an ISH assay. Osteosarcoma cells' proliferation and migration/invasion ability changes were measured by a CCK-8/EDU assay and a transwell assay respectively. ROCK1 expression changes were checked by a qRT-PCR assay and a western blot assay. Targeted binding effects between miR-335-5p/miR-1972 and ROCK1 or DANCR were verified by a dual luciferase reporter assay and a RIP assay. In vivo experiments including a nude formation assay as well as a CT scan were applied to detect tumor growth and metastasis changes in animal level.
Results
In the present study, an elevated DNACR was found in osteosarcoma tissue specimens and in osteosarcoma cell lines, and the elevated DNACR was closely correlated with poor prognosis in clinical patients. Functional experiments illustrated that a depression of DANCR suppressed ROCK1-mediated proliferation and metastasis in osteosarcoma cells. The results of western blot assays and qRT-PCR assays revealed that DANCR regulated ROCK1 via crosstalk with miR-335-5p and miR-1972. Further cellular behavioral experiments demonstrated that DNACR promoted ROCK1-meidated proliferation and metastasis through decoying both miR-335-5p and miR-1972. Finally, the outcomes of in vivo animal models showed that DANCR promoted tumor growth and lung metastasis of osteosarcoma.
Conclusions
LncRNA DANCR work as an oncogene and promoted ROCK1-mediated proliferation and metastasis through acting as a competing endogenous RNA (ceRNA) in osteosarcoma.
https://ift.tt/2ryvFMO
Discovery of a Potent and Mutant-Selective EGFR Inhibitor that Overcomes T790M-Mediated Resistance in Lung Cancer
Abstract
Background
Despite remarkable activity in epidermal growth factor receptor (EGFR)-mutant lung cancer patients, the clinical efficacy of EGFR tyrosine kinase inhibitors (TKIs) is limited by the emergence of acquired resistance, which is mostly caused by a secondary T790M mutation. Fortunately, newly developed, mutant-selective EGFR-TKIs against T790M have been proven as an effective therapeutic approach although only osimertinib has received the FDA approval until now.
Objective
To determine the in vitro and in vivo efficacy of a new EGFR TKI, OBX1-012 in cells with mutant EGFR.
Methods
Effects of OBX1-012 on cellular viability and EGFR-related signaling were determined in EGFR-mutant non-small cell lung cancer (NSCLC) cells, including cells harboring T790M mutations. In addition, in vivo efficacy of OBX1-012 was evaluated in xenograft models.
Results
We report the discovery and preclinical assessment of another novel, mutant-selective EGFR-TKI, OBX1-012. Compared with other mutant-selective EGFR-TKIs such as olumitinib and osimertinib, it showed similar potency and selectivity for mutant EGFR. OBX1-012 treatment was highly effective against human EGFR-mutant lung cancer models with or without EGFR T790M, not only in vitro but also in vivo. However, OBX1-012 like other EGFR-TKIs failed to exhibit efficacy for the exon 20 insertion mutation or C797S mutation, which was generated by site-directed mutagenesis and stable transfection of Ba/F3 cells.
Conclusions
These results identify OBX1-012 as a highly effective, mutant-selective EGFR-TKI for the treatment of T790M-mediated resistance in NSCLC.
https://ift.tt/2rFmEkW
[The French health care funding system for research and innovation in oncology].
| Related Articles |
[The French health care funding system for research and innovation in oncology].
Bull Cancer. 2018 May 07;:
Authors: Wiernik H, Katz G, Coulonjou H, Salagnac A, Kletz F, Thariat J
Abstract
INTRODUCTION: This article provides an overview of the French health system with respect to allocation of public resources to hospitals, to encourage research and innovation, particularly in the field of oncology. It is explained in a historical, economic and scientific perspective.
RESULTS: Important structural and conceptual reforms (T2A, HPST law, etc.) have been carried out. These have significantly impacted the way public funding is allocated. Funding of innovation and research has been modified into a more incentive logic, aimed at strengthening competitiveness between all health care actors. The funding allocation system has evolved towards a more ubiquitous redistribution, including non-academic and private institutions. The baseline endowment includes indicators relating to scientific publications (60% of the endowment), teaching (25%) and clinical trials (15%). Research funding is then redistributed by regional health agencies, and used in health care institutions at the discretion of the directorates. Other funding sources such as calls for grants, funding for mobile research centers and teams, tumor banks and temporary user licenses are also part of the funding by the French Ministry of health.
CONCLUSION: Changes in the health research funding system have an incentive purpose. They have significantly modified the global healthcare landscape. Feedback on these changes will be necessary to assess the success of the reinforcement of the dynamics of research and innovation.
PMID: 29747854 [PubMed - as supplied by publisher]
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Cholestatic jaundice: a unique presentation leading to the diagnosis of HLH with Hodgkin lymphoma, HIV and EBV
Haemophagocytic lymphohistiocytosis (HLH) is a syndrome of dysregulated immune activity with macrophage activation that can manifest as pancytopenia, coagulopathy and other laboratory abnormalities, usually progressing to multiorgan failure and death. This report documents the rarely reported association between HLH and Hodgkin's lymphoma (HL) with simultaneous HIV and Epstein-Barr virus (EBV) and complete resolution with chemotherapy. The patient initially presented with cholestatic jaundice. He was then found to have HL associated with HLH with coexistent HIV and EBV viraemia. A-Brentuximab-VD regimen for the lymphoma was initiated, resulting in rapid resolution of HLH and ultimately remission of HL. HLH is a syndrome known to have high mortality; thus, early diagnosis and prompt treatment are crucial. Usual presentation includes non-specific symptoms and can easily be overlooked. This case highlights the importance of diagnosing the condition in unusual settings and attempting treatment by targeting the cause of HLH, HL in our case.
https://ift.tt/2jPtscj
Lateral semicircular canal osteoma presenting as chronic postaural fistula
Temporal bone osteoma is an unusual pathology which can occur by birth or can be acquired and mostly involves the tympanomastoid segment of the temporal bone. Osteomas arising from the otic capsule are extremely rare, and there has been only one other report of a lateral semicircular canal osteoma in the literature. We report a similar case of an acquired lateral canal osteoma which presented as a chronic postaural fistula in an ear previously operated for paediatric cholesteatoma.
https://ift.tt/2IiMZfK
Urothelial carcinoma of an allograft ureter 10 years after deceased donor kidney transplantation
The incidence of urothelial carcinoma (UC; formerly transitional cell carcinoma) is higher among renal transplant recipients compared with the general population. Upper urinary tract UC (UUT-UC) of allograft urothelium is a rare event with approximately 40 cases reported in the literature. Herein, we describe the clinical presentation and management of UUT-UC in a transplant ureter 10 years after deceased donor kidney transplantation.
https://ift.tt/2jSvBnK
Granuloma formation associated with patellar tendon necrosis in response to Ethibond confirmed by histopathological examination
The aim of this study is to describe a case of delayed granuloma formation associated with tendon necrosis in response to Ethibond confirmed by histopathological examination and to review and discuss the related literature. A 40-year-old woman underwent a patellar tendon repair with Krakow-like #5 Ethibond sutures. Four years after the repair, she noticed progressive soreness with knee extension and swelling. An ultrasound examination revealed a proximal partial patellar tendon rupture. Based on these findings, the patient was advised to undergo surgical intervention due to a diagnosis of re-rupture. Tendinosis, fibrosis and necrosis scar tissue surrounding the previous suture were observed and excised, and samples were sent for histopathological and microbiological examination. Stripping of the patellar paratenon was performed. Surprisingly, a giant cell foreign body reaction surrounding the synthetic refringent material, as well as polymorphonuclear cells surrounding the necrotic tendon, was reported.
https://ift.tt/2jPtoJB
Unravelling the NERDS syndrome
A 22-year-old man presented with symmetric polyarthritis, pruritus and deviation of angle of mouth to the right side since the last 7 years. His symptoms were persistent despite receiving ayurvedic medications and symptomatic therapy. Examination revealed dry skin, cutaneous nodules, xanthelasma, periarticular non-tender swellings, pitting oedema of hands and feet and lower motor neuron type right facial palsy. Haematological investigations revealed eosinophilia and skin biopsy had cutaneous eosinophilic infiltration. The constellation of above findings comprises the nodules, eosinophilia, rheumatism, dermatitis and swelling syndrome. It a rare syndrome with few reported cases in literature. The patient was started on oral corticosteroids which was subsequently tapered and methotrexate therapy. His polyarthritis and skin rashes resolved with therapy. He has been followed-up for 2 years and is presently asymptomatic for the last 1 year.
https://ift.tt/2Ier9dq
Improvement of primary biliary cholangitis (PBC) under treatment with sulfasalazine and abatacept
Description
A 51-year-old female patient was diagnosed with primary biliary cholangitis (PBC) in 2012 and rheumafactor-positive, Anti-citrullinated protein antibodies (ACPA)-positive rheumatoid arthritis (RA) in 2013. The diagnosis of a PBC was confirmed by liver biopsy showing portal inflammatory infiltrates with non-suppurative inflammatory lesions of the biliary duct (figure 1). PBC has been treated with ursodeoxycholic acid since 2012.
Figure 1
Dense lymphocytic infiltrates in portal tracts affecting small portal bile ducts, moderate lobular infiltrates.
After diagnosis of RA (initial Disease Activity Score 28 (DAS 28)=6.43), therapy was initiated with leflunomide 20 mg/day and low-dose oral glucocorticoids, tapered from 20 mg/day to zero over 12 weeks. Remission was reached within 4 months (DAS 28=1.84). However, elevated transaminases were detected. As a consequence, leflunomide was switched to sulfasalazine in September 2013. After an increase of activity of RA under sulfasalazine, abatacept 750 mg every 4 weeks was...
https://ift.tt/2IfEhPB
Cavernous sinus meningioma presenting as third nerve palsy in pregnancy
A 33-year-old female patient presented with diplopia and left eye ptosis 26 weeks into her first pregnancy. No investigation was conducted at the time and her symptoms subsided 4 weeks post partum. This same phenomenon occurred during second pregnancy at 20 weeks of gestation, with patient becoming symptom-free again 6 weeks after giving birth. MRI revealed a lesion in the left cavernous sinus in keeping with a meningioma. Due to the surgically challenging location, the lesion was treated with gamma knife radiosurgery. To date, the patient remains asymptomatic with no progression on follow-up imaging 9 years on.
https://ift.tt/2Icr4Lm
Fibrosing mediastinitis-related pulmonary artery and vein stenosis-limiting chemotherapy
Description
A 74-year-old woman presented for second opinion of dyspnoea management. Her medical history included breast cancer treated with mastectomy, doxorubicin, cyclophosphamide and tamoxifen. She developed recurrent metastatic disease in the mediastinum, managed with 89 six-week cycles of paclitaxel over 10 years that was well tolerated and effective in stabilising the disease initially but eventually discontinued due to new sternal metastasis diagnosed on imaging and increasing dyspnoea. Examination revealed diminished left-sided breath sounds. Routine labs were normal. Echocardiogram showed normal left ventricular function and dilated right chambers. Repeat chest CT demonstrated: (1) extensive calcification and soft tissue mass in the anterior mediastinum consistent with fibrosing mediastinitis (FM); (2) severe left pulmonary artery stenosis (PAS, figure 1); and (3) an infiltrating soft tissue density in the pericardium. Subsequent pericardial tissue biopsy showed non-specific fibrosis. Pulmonary angiography showed bilateral PAS. Angiographic and surgical interventions were deferred due to...
https://ift.tt/2IeTnoi
Recovery of brain abscess-induced stuttering after neurosurgical intervention
Stuttering occurs in approximately 5% of all children and 1% of adults. One type, neurogenic stuttering, is usually attributable to strokes or other structural damages to the brain areas that are responsible for language fluency. Here, we present the first case of neurogenic stuttering caused by a brain abscess. The patient was a 60-year-old man admitted for a seizure and administered an anticonvulsant, after which he began stuttering. MRI revealed a brain abscess in the left frontal lobe that extended to the dorsolateral prefrontal cortex (BA (Brodmann's area) 9 and 46), frontal eye field (BA 8) and premotor cortex and supplementary motor area (BA 6). After neurosurgical drainage and antibiotic treatment, the symptoms had resolved. This case is unique in that the therapeutic effects and localisation of the cause of stuttering were rapidly identified, allowing for a more accurate description of the neural circuitry related to stuttering.
https://ift.tt/2jPtild
Unusual cause of brachial palsy with diaphragmatic palsy
We report a preterm neonate born with respiratory distress. The neonate was found to have diaphragmatic palsy and brachial palsy. The neonate was born by caesarean section and there was no history of birth trauma. On examination, there was bilateral congenital talipes equinovarus and a scar was present on the forearm. The mother had a history of chickenpox during the 16 weeks of pregnancy for which no treatment was sought. On investigation, PCR for varicella was found to be positive in the neonate.
https://ift.tt/2IfEbHJ
Solitary calvarial haemangioma presenting as metastatic renal cell carcinoma
Renal cell carcinoma is the most common renal tumour in adult that often metastasises to the lung, liver or bone. Head and neck lesions are uncommon with no early warning signs and presents with overt metastases at primary presentation in 25%–30% of reported cases. The incidence of haemangiomas that suggest malignancy are similar to that of bone metastasis. Calvarial haemangiomas usually present as asymptomatic and discovered incidentally on imaging or postmortem examination. We report a case where an initial diagnosis of benign tumour of the skull was made based on clinical presentation and calvarial haemangioma on CT head but was confirmed as metastatic clear cell carcinoma of the kidney after histopathological results. Skull metastases are rare and present late in the course of the disease. It is unusual for metastatic lesion to be the primary presentation in a clinically silent renal cell carcinoma.
https://ift.tt/2I9gkxe
Dichorionic twins discordant for body-stalk anomaly: a management challenge
Body-stalk anomaly is a sporadic and rare maldevelopment disorder characterised by large abdominal wall defect, spinal deformity and rudimentary umbilical cord. It is considered a lethal condition as there are only few reports of survival but there was at least one case of long-term survival after neonatal surgery.
Differential diagnosis includes isolated omphalocele or gastroschisis, short umbilical cord, amniotic band, limb body-wall complex and other polymalformative syndromes.
There are few reports about the expectant prenatal management of the body stalk anomaly as the majority of prenatal diagnosed cases undergo early elective termination. Twin pregnancies discordant for the anomaly represent a challenge to prenatal management as a healthy fetus should also be considered.
We describe a case of dichorionic-diamniotic twins discordant for body stalk anomaly which underwent selective feticide of the affected fetus late in pregnancy, in accordance with parents' decision focused on the neonatal well-being of the unaffected twin.
https://ift.tt/2IfE8M3
Surprising pathological and clinical manifestations of miliary tuberculosis
We report a surprising pathological finding of miliary tuberculosis (TB) in a 49-year-old Chuukese, immunocompetent woman who was initially admitted to the hospital for a 1-month duration of chronic abdominal pain and intermittent fevers. Her clinical symptoms did not improve despite treatment with vancomycin and piperacillin–tazobactam. Based on the primary abdominal CT findings suggesting advanced ovarian cancer with omental metastatic disease, further workup with omental core biopsy was performed and demonstrated acute neutrophilic necrosis without malignant cells or granulomata. Within the omental tissue, however, many organisms stained positive for acid-fast bacilli despite lack of typical granulomata. The diagnosis of genitourinary TB was confirmed by urine Mycobacterium tuberculosis/rifampin automated molecular rapid nucleic acid amplification test. The chest CT showed a millet seed pattern of infiltration which is a hallmark for miliary TB. After initiation of multidrug TB therapy, her fever and abdominal pain drastically improved.
https://ift.tt/2jSvR62
Unilateral lung agenesis, hiatal hernia and atrioventricular septal defect: a rare combination of congenital anomalies
Unilateral lung agenesis is a relatively rare congenital anomaly with a reported incidence of 1 in 15 000 births. It is frequently associated with other congenital malformations. Some of the sequelae of lung agenesis are potentially life-threatening. Here, we report a case of left lung agenesis in association with hiatal hernia and atrioventricular septal defect, a rare combination of anomalies which have not been described previously in the literature.
https://ift.tt/2IgAu4G
Disseminated cryptococcosis in HIV negative patient
A 52-year-old white diabetic male with 4-weeks history of persistent cough followed by headache, drenching night sweats, low-grade fever, worsening photophobia, nausea and vomiting was presented. Examination was significant for photophobia and diminution of vision. His spinal fluid and blood cultures were positive for Cryptococcus neoformans. Intravenous fluconazole were given for 2 weeks followed by oral fluconazole. There was significant improvement in systemic and ocular symptoms. HIV serology was negative, but his CD4 counts were low with inverted CD4:CD8 ratio.
https://ift.tt/2jSUJLc
An interesting case of lymphadenopathy
Description
A 43-year-old man, a known case of diabetes mellitus and hypertension (both well controlled), with no history suggestive of high-risk sexual behaviour, presented with a painless swelling over the left side of the neck since 30 days which was insidious in onset and gradually progressive; fever since 15 days which was of sudden onset, intermittent, relieved with medications and was associated with generalised bodyache; diarrhoea since 3 days which was sudden in onset, foul smelling, watery, non-bloody, 7–8 episodes per day. He had lost 4 kg of weight in 15 days. He was a vegetarian, did not keep cats as pets and was not known to be having an immunocompromised state.
On clinical examination, only the lymph nodes in the posterior triangle of the left side of the neck were palpable. These were non-tender and were not matted.
Investigations showed anti-toxoplasma antibodies IgM and IgG (done by ELISA...
https://ift.tt/2Ifu4CP
Genetic variants in the HLA class II region associated with risk of cutaneous squamous cell carcinoma
Abstract
Background
The immune system has been implicated in the pathophysiology of cutaneous squamous cell carcinoma (cSCC) as evidenced by the substantially increased risk of cSCC in immunosuppressed individuals. Associations between cSCC risk and single nucleotide polymorphisms (SNPs) in the HLA region have been identified by genome-wide association studies (GWAS). The translation of the associated HLA SNPs to structural amino acids changes in HLA molecules has not been previously elucidated.
Methods
Using data from a GWAS that included 7238 cSCC cases and 56,961 controls of non-Hispanic white ancestry, we imputed classical alleles and corresponding amino acid changes in HLA genes. Logistic regression models were used to examine associations between cSCC risk and genotyped or imputed SNPs, classical HLA alleles, and amino acid changes.
Results
Among the genotyped SNPs, cSCC risk was associated with rs28535317 (OR = 1.20, p = 9.88 × 10− 11) corresponding to an amino-acid change from phenylalanine to leucine at codon 26 of HLA-DRB1 (OR = 1.17, p = 2.48 × 10− 10). An additional independent association was observed for a threonine to isoleucine change at codon 107 of HLA-DQA1 (OR = 1.14, p = 2.34 × 10− 9). Among the classical HLA alleles, cSCC was associated with DRB1*01 (OR = 1.18, p = 5.86 × 10− 10). Conditional analyses revealed additional independent cSCC associations with DQA1*05:01 and DQA1*05:05. Extended haplotype analysis was used to complement the imputed haplotypes, which identified three extended haplotypes in the HLA-DR and HLA-DQ regions.
Conclusions
Associations with specific HLA-DR and -DQ alleles are likely to explain previously observed GWAS signals in the HLA region associated with cSCC risk.
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Genetic variants in the HLA class II region associated with risk of cutaneous squamous cell carcinoma
Abstract
Background
The immune system has been implicated in the pathophysiology of cutaneous squamous cell carcinoma (cSCC) as evidenced by the substantially increased risk of cSCC in immunosuppressed individuals. Associations between cSCC risk and single nucleotide polymorphisms (SNPs) in the HLA region have been identified by genome-wide association studies (GWAS). The translation of the associated HLA SNPs to structural amino acids changes in HLA molecules has not been previously elucidated.
Methods
Using data from a GWAS that included 7238 cSCC cases and 56,961 controls of non-Hispanic white ancestry, we imputed classical alleles and corresponding amino acid changes in HLA genes. Logistic regression models were used to examine associations between cSCC risk and genotyped or imputed SNPs, classical HLA alleles, and amino acid changes.
Results
Among the genotyped SNPs, cSCC risk was associated with rs28535317 (OR = 1.20, p = 9.88 × 10− 11) corresponding to an amino-acid change from phenylalanine to leucine at codon 26 of HLA-DRB1 (OR = 1.17, p = 2.48 × 10− 10). An additional independent association was observed for a threonine to isoleucine change at codon 107 of HLA-DQA1 (OR = 1.14, p = 2.34 × 10− 9). Among the classical HLA alleles, cSCC was associated with DRB1*01 (OR = 1.18, p = 5.86 × 10− 10). Conditional analyses revealed additional independent cSCC associations with DQA1*05:01 and DQA1*05:05. Extended haplotype analysis was used to complement the imputed haplotypes, which identified three extended haplotypes in the HLA-DR and HLA-DQ regions.
Conclusions
Associations with specific HLA-DR and -DQ alleles are likely to explain previously observed GWAS signals in the HLA region associated with cSCC risk.
https://ift.tt/2IAip4F
Genetic variants in the HLA class II region associated with risk of cutaneous squamous cell carcinoma
Abstract
Background
The immune system has been implicated in the pathophysiology of cutaneous squamous cell carcinoma (cSCC) as evidenced by the substantially increased risk of cSCC in immunosuppressed individuals. Associations between cSCC risk and single nucleotide polymorphisms (SNPs) in the HLA region have been identified by genome-wide association studies (GWAS). The translation of the associated HLA SNPs to structural amino acids changes in HLA molecules has not been previously elucidated.
Methods
Using data from a GWAS that included 7238 cSCC cases and 56,961 controls of non-Hispanic white ancestry, we imputed classical alleles and corresponding amino acid changes in HLA genes. Logistic regression models were used to examine associations between cSCC risk and genotyped or imputed SNPs, classical HLA alleles, and amino acid changes.
Results
Among the genotyped SNPs, cSCC risk was associated with rs28535317 (OR = 1.20, p = 9.88 × 10− 11) corresponding to an amino-acid change from phenylalanine to leucine at codon 26 of HLA-DRB1 (OR = 1.17, p = 2.48 × 10− 10). An additional independent association was observed for a threonine to isoleucine change at codon 107 of HLA-DQA1 (OR = 1.14, p = 2.34 × 10− 9). Among the classical HLA alleles, cSCC was associated with DRB1*01 (OR = 1.18, p = 5.86 × 10− 10). Conditional analyses revealed additional independent cSCC associations with DQA1*05:01 and DQA1*05:05. Extended haplotype analysis was used to complement the imputed haplotypes, which identified three extended haplotypes in the HLA-DR and HLA-DQ regions.
Conclusions
Associations with specific HLA-DR and -DQ alleles are likely to explain previously observed GWAS signals in the HLA region associated with cSCC risk.
from Cancer via ola Kala on Inoreader https://ift.tt/2IAip4F
via IFTTT
Genetic variants in the HLA class II region associated with risk of cutaneous squamous cell carcinoma
Abstract
Background
The immune system has been implicated in the pathophysiology of cutaneous squamous cell carcinoma (cSCC) as evidenced by the substantially increased risk of cSCC in immunosuppressed individuals. Associations between cSCC risk and single nucleotide polymorphisms (SNPs) in the HLA region have been identified by genome-wide association studies (GWAS). The translation of the associated HLA SNPs to structural amino acids changes in HLA molecules has not been previously elucidated.
Methods
Using data from a GWAS that included 7238 cSCC cases and 56,961 controls of non-Hispanic white ancestry, we imputed classical alleles and corresponding amino acid changes in HLA genes. Logistic regression models were used to examine associations between cSCC risk and genotyped or imputed SNPs, classical HLA alleles, and amino acid changes.
Results
Among the genotyped SNPs, cSCC risk was associated with rs28535317 (OR = 1.20, p = 9.88 × 10− 11) corresponding to an amino-acid change from phenylalanine to leucine at codon 26 of HLA-DRB1 (OR = 1.17, p = 2.48 × 10− 10). An additional independent association was observed for a threonine to isoleucine change at codon 107 of HLA-DQA1 (OR = 1.14, p = 2.34 × 10− 9). Among the classical HLA alleles, cSCC was associated with DRB1*01 (OR = 1.18, p = 5.86 × 10− 10). Conditional analyses revealed additional independent cSCC associations with DQA1*05:01 and DQA1*05:05. Extended haplotype analysis was used to complement the imputed haplotypes, which identified three extended haplotypes in the HLA-DR and HLA-DQ regions.
Conclusions
Associations with specific HLA-DR and -DQ alleles are likely to explain previously observed GWAS signals in the HLA region associated with cSCC risk.
from Cancer via ola Kala on Inoreader https://ift.tt/2IAip4F
via IFTTT
Genetic variants in the HLA class II region associated with risk of cutaneous squamous cell carcinoma
Abstract
Background
The immune system has been implicated in the pathophysiology of cutaneous squamous cell carcinoma (cSCC) as evidenced by the substantially increased risk of cSCC in immunosuppressed individuals. Associations between cSCC risk and single nucleotide polymorphisms (SNPs) in the HLA region have been identified by genome-wide association studies (GWAS). The translation of the associated HLA SNPs to structural amino acids changes in HLA molecules has not been previously elucidated.
Methods
Using data from a GWAS that included 7238 cSCC cases and 56,961 controls of non-Hispanic white ancestry, we imputed classical alleles and corresponding amino acid changes in HLA genes. Logistic regression models were used to examine associations between cSCC risk and genotyped or imputed SNPs, classical HLA alleles, and amino acid changes.
Results
Among the genotyped SNPs, cSCC risk was associated with rs28535317 (OR = 1.20, p = 9.88 × 10− 11) corresponding to an amino-acid change from phenylalanine to leucine at codon 26 of HLA-DRB1 (OR = 1.17, p = 2.48 × 10− 10). An additional independent association was observed for a threonine to isoleucine change at codon 107 of HLA-DQA1 (OR = 1.14, p = 2.34 × 10− 9). Among the classical HLA alleles, cSCC was associated with DRB1*01 (OR = 1.18, p = 5.86 × 10− 10). Conditional analyses revealed additional independent cSCC associations with DQA1*05:01 and DQA1*05:05. Extended haplotype analysis was used to complement the imputed haplotypes, which identified three extended haplotypes in the HLA-DR and HLA-DQ regions.
Conclusions
Associations with specific HLA-DR and -DQ alleles are likely to explain previously observed GWAS signals in the HLA region associated with cSCC risk.
https://ift.tt/2IAip4F
An extract of Synedrella nodiflora (L) Gaertn exhibits antidepressant properties through monoaminergic mechanisms
Abstract
Synedrella nodiflora (SNE) has been used traditionally for many neurological conditions and some of these neuroactive effects have been scientifically substantiated. The usefulness of SNE in depression has however not been investigated despite the availability of data in other disease models indicating it may be useful. The present study therefore examined the effect of SNE in acute murine models of depression and the possible mechanisms mediating its activities in these models. Preliminary qualitative phytochemical and high performance liquid chromatography (HPLC) screening were conducted on SNE. The behavioural effects of SNE (100, 300 and 1000 mg/kg) pre-treated mice were examined in the forced swimming (FST) and tail suspension (TST) tests. Behavioural events such as mobility (swimming, climbing, curling and climbing), and immobility, were scored. The possible involvement of monoamines in the effects of SNE was assessed in the TST by pre-treating mice with α-methyldopa, reserpine and para-chlorophenylalanine (pCPA) in separate experiments. Flavonoids, tannins, saponins, alkaloids, cardiac glycosides, coumarins, triterpenes, sterols, anthraquinones and phenolic compounds were present in SNE. HPLC analysis revealed the presence of two major constituents observed at retention times 42.56 and 46.51 min, with percentage composition of 45.72% and 36.88% respectively. SNE significantly reduced immobility scores in both FST and TST, suggesting antidepressant effects. The antidepressant properties of SNE were reversed by the pre-treatment of α-methyldopa, reserpine and pCPA, suggesting a possible involvement of monoamines (noradrenaline and serotonin) in its mechanism(s) of actions. SNE exhibits antidepressant effects, possibly mediated through an interplay of enhancement of noradrenergic and serotoninergic mechanisms.
from Cancer via ola Kala on Inoreader https://ift.tt/2G83zNJ
via IFTTT
An extract of Synedrella nodiflora (L) Gaertn exhibits antidepressant properties through monoaminergic mechanisms
Abstract
Synedrella nodiflora (SNE) has been used traditionally for many neurological conditions and some of these neuroactive effects have been scientifically substantiated. The usefulness of SNE in depression has however not been investigated despite the availability of data in other disease models indicating it may be useful. The present study therefore examined the effect of SNE in acute murine models of depression and the possible mechanisms mediating its activities in these models. Preliminary qualitative phytochemical and high performance liquid chromatography (HPLC) screening were conducted on SNE. The behavioural effects of SNE (100, 300 and 1000 mg/kg) pre-treated mice were examined in the forced swimming (FST) and tail suspension (TST) tests. Behavioural events such as mobility (swimming, climbing, curling and climbing), and immobility, were scored. The possible involvement of monoamines in the effects of SNE was assessed in the TST by pre-treating mice with α-methyldopa, reserpine and para-chlorophenylalanine (pCPA) in separate experiments. Flavonoids, tannins, saponins, alkaloids, cardiac glycosides, coumarins, triterpenes, sterols, anthraquinones and phenolic compounds were present in SNE. HPLC analysis revealed the presence of two major constituents observed at retention times 42.56 and 46.51 min, with percentage composition of 45.72% and 36.88% respectively. SNE significantly reduced immobility scores in both FST and TST, suggesting antidepressant effects. The antidepressant properties of SNE were reversed by the pre-treatment of α-methyldopa, reserpine and pCPA, suggesting a possible involvement of monoamines (noradrenaline and serotonin) in its mechanism(s) of actions. SNE exhibits antidepressant effects, possibly mediated through an interplay of enhancement of noradrenergic and serotoninergic mechanisms.
https://ift.tt/2G83zNJ
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