Project description:For over a decade, the mainstay of multiple myeloma therapy has been small molecules that directly attack malignant plasma cell biology. However, potent immunotherapies have recently emerged, transforming the myeloma therapeutic landscape. Here we first review new promising strategies to target plasma cells through protein homeostasis and epigenetic modulators. We then discuss emerging immunotherapy strategies that are leading to dramatic results in patients. Finally, we focus on recent preclinical data suggesting that enforcing cell-surface antigen expression through small molecules may enhance immunotherapy efficacy and avoid resistance. We argue that these emerging observations point the way toward potential convergence between drug classes. With recent rapid progress we may finally be on the verge of the 'C' word: a cure for myeloma.
Project description:Arrestins play a key role in homologous desensitization of G protein-coupled receptors (GPCRs) and regulate several other vital signaling pathways in cells. Considering the critical roles of these proteins in cellular signaling, surprisingly few disease-causing mutations in human arrestins were described. Most of these are loss-of-function mutations of visual arrestin-1 that cause excessive rhodopsin signaling and hence night blindness. Only one dominant arrestin-1 mutation was discovered so far. It reduces the thermal stability of the protein, which likely results in photoreceptor death via unfolded protein response. In case of the two nonvisual arrestins, only polymorphisms were described, some of which appear to be associated with neurological disorders and altered response to certain treatments. Structure-function studies revealed several ways of enhancing arrestins' ability to quench GPCR signaling. These enhanced arrestins have potential as tools for gene therapy of disorders associated with excessive signaling of mutant GPCRs.
Project description:Carcinoid tumors in pregnant women are rare, and there have been no previous studies of atypical carcinoid tumor reported in pregnancy. Also, pseudomesotheliomatous manifestation in atypical carcinoid is an extremely rare finding, there being only two cases reported. Here, we present the first case of pseudomesotheliomatous manifestation of atypical carcinoid in a pregnant woman. Upon image analysis, we found that atypical carcinoids with multiple metastatic lesions can exhibit variability in vascularity and metabolism, resulting in heterogeneous image characteristics among metastatic lesions, even those with identical histology. In addition, even with extensive metastasis, patients can exhibit good performance explained by long-standing presentation of indolent cancer.
Project description:Metabolomics enables the profiling of large numbers of small molecules in cells, tissues and biological fluids. These molecules, which include amino acids, carbohydrates, lipids, nucleotides and their metabolites, can be detected quantitatively. Metabolomic methods, often focused on the information-rich analytical techniques of NMR spectroscopy and mass spectrometry, have potential for early diagnosis, monitoring therapy and defining disease pathogenesis in many therapeutic areas, including rheumatic diseases. By performing global metabolite profiling, also known as untargeted metabolomics, new discoveries linking cellular pathways to biological mechanisms are being revealed and are shaping our understanding of cell biology, physiology and medicine. These pathways can potentially be targeted to diagnose and treat patients with immune-mediated diseases.
Project description:This research mainly aims to develop a generalized cure rate model, estimate the proportion of cured patients and their survival rate, and identify the risk factors associated with infectious diseases. The generalized cure rate model is based on bounded cumulative hazard function, which is a non-mixture model, and is developed using a two-parameter Weibull distribution as the baseline distribution, to estimate the cure rate using maximum likelihood method and real data with R and STATA software. The results showed that the cure rate of tuberculosis (TB) patients was 26.3%, which was higher than that of TB patients coinfected with human immunodeficiency virus (HIV; 23.1%). The non-parametric median survival time of TB patients was 51 months, while that of TB patients co-infected with HIV was 33 months. Moreover, no risk factors were associated with TB patients co-infected with HIV, while age was a significant risk factor for TB patients among the suspected risk factors considered. Furthermore, the bounded cumulative hazard function was extended to accommodate infectious diseases with co-infections by deriving an appropriate probability density function, determining the distribution, and using real data. Governments and related health authorities are also encouraged to take appropriate actions to combat infectious diseases with possible co-infections.
Project description:Lipoma is the most common benign soft tissue tumor. Lipomas are relatively uncommon tumours in the oral cavity accounting only 1-4 %. Half of oral lipomas are in the cheek and the remaining is found in the tongue, floor of the mouth, lips, palate, and gingival mucosa. We are reporting a case of lipoma that occurred in the hard palate, which is extremely rare.
Project description:Mucinous cholangiocarcinoma is extremely rare and its clinicopathological features remain unclear. The present study aimed to analyze published data on mucinous cholangiocarcinoma. Medical databases were searched from 1980 to 2016, and clinicopathological data for 16 mucinous cholangiocarcinoma patients were obtained. Characteristic imaging findings, including hypovascular tumor with peripheral enhancement on computed tomography and angiography, extremely high intensity on T2-weighted magnetic resonance images, intratumoral calcification and luminal communication between the tumor and bile duct on cholangiography, were noted. Mucinous cholangiocarcinoma was correctly diagnosed in one patient only, with some patients diagnosed as low-malignant biliary cystic tumors preoperatively. Five cases were followed up after the first medical examination, and three of these were initially diagnosed as biliary cystadenoma or intraductal papillary neoplasm of the bile duct. All five tumors showed marked enlargement within 4 months of follow up. Macroscopically, the resected tumors were non-cystic/solid in seven cases, and cystic in seven. Tumor diameter ranged from 5 cm to 22 cm, and mucoid cut surface, lobulation, lack of capsule and papillary growth were observed. Microscopically, co-existing intraductal papillary neoplasm of the bile duct was noted in three of five patients with available data. Nine of 10 cases in whom the pathological stage was reported had advanced disease with lymph node and/or distant metastasis, and 5-year survival was achieved in one microinvasive case only. Overall 1- and 3-year survival rates were 60.1% and 40.1%, respectively. The possibility of mucinous cholangiocarcinoma should be considered when biliary cystic tumors are detected on imaging modalities, despite the rarity of this tumor.
Project description:Tau, a member of the microtubule-associated proteins, is a known component of the neuronal cytoskeleton; however, in the brain tissue, it is involved in other vital functions beyond maintaining the cellular architecture. The pathologic tau forms aggregates inside the neurons and ultimately forms the neurofibrillary tangles. Intracellular and extracellular accumulation of different tau isoforms, including dimers, oligomers, paired helical filaments and tangles, lead to a highly heterogenous group of diseases named "Tauopathies". About twenty-six different types of tauopathy diseases have been identified that have different clinical phenotypes or pathophysiological characteristics. Although all these diseases are identified by tau aggregation, they are distinguishable based on the specific tau isoforms, the affected cell types and the brain regions. The neuropathological and phenotypical heterogeneity of these diseases impose significant challenges for discovering new diagnostic and therapeutic strategies. Here, we review the recent literature on tau protein and the pathophysiological mechanisms of tauopathies. This article mainly focuses on physiologic and pathologic tau and aims to summarize the upstream and downstream events and discuss the current diagnostic approaches and therapeutic strategies.