Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UNIPROT:P50583 (asymmetrical)
12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cancer is now known to be a genetic disease. In tumor development, cell nuclei undergo mutations, which can result in cytologically visible chromosome aberrations. The aneuploid errors may involve amplification or deletion of whole chromosomes or segments thereof. David Hansemann [1858-1920] and Theodor Boveri [1862-1915] were major contributors to early debates on the relationship between chromosomal defects, tumorigenesis and malignancies. In 1890, Hansemann observed asymmetrical nuclear divisions in human epithelial cancers. In these abnormal, but bipolar, divisions, a fraction of the chromosomes fails to segregate properly. Hansemann carefully documented the occurrence of asymmetric divisions in a wide variety of tumors. However, he remained a lifelong skeptic with regard to whether such events could be considered the underlying cause of tumors. Almost a quarter of a century after Hansemann's initial observations, Boveri considered the origin of tumors based on his earlier recognition of the functional specificity of each chromosome. He also explicitly drew on Hansemann's observations in proposing a model for tumorigenesis. Its central tenet was that a tumor typically originates from a single cell that has inherited a defined, but incorrectly combined, set of chromosomes. The rare occurrence of a pluripolar spindle represented Boveri's paradigm for a type of abnormal mitosis that can produce a host of random chromosomal combinations. He suggested that some of these combinations will induce tumorous transformation, and will inevitably arise occasionally. Since pluripolar and unbalanced bipolar divisions fail to distribute the hereditary chromatic material correctly, both of these mechanisms can give rise to tumor progenitors.
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PMID:Reappraisal of the Hansemann-Boveri hypothesis on the origin of tumors. 1631 17

Several observations imply that atypical rheumatic manifestations may be associated with occult neoplasia. A 71-year-old woman was admitted to the hospital three times in 2 years. Initially, she was admitted for investigation of an iron-deficient anemia associated with upper intestinal tract symptoms. Endoscopy revealed hiatus hernia, esophagitis, and duodenal ulcer with a Helicobacter pylori infection, but there were no signs of malignancy, and the patient received appropriate drug treatment. Two years later, she presented with arthralgias concerning the upper and lower limbs in an asymmetrical distribution, low fever, and persistence of the anemia, despite the treatment she had received and the fact that her gastrointestinal symptoms had long ceased. Immunological assays showed no specific rheumatic disorder, and the patient was discharged after showing significant improvement with the use of COX-2 selective NSAIDs. Finally, 4 months later, she was readmitted with worsening of the arthralgias, arthritis in the right radiocarpal joint, and severe anemia. Hematemesis that occurred during her hospital stay led to an emergency endoscopy and the diagnosis of gastric adenocarcinoma. Only a few cases have been reported so far concerning rheumatic manifestations as signs of an occult gastric cancer. Thus, there must be some degree of suspicion when dealing with patients with anemia and rheumatic symptoms that cannot be classified into a particular rheumatologic entity, because they might conceal a gastrointestinal malignancy not yet evident.
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PMID:Rheumatic-like syndrome as a symptom of underlying gastric cancer. 1657 85

A case with brain metastasis involving bilateral middle cerebellar peduncles (bMCP) was reported. A 71-year-old male with gastric cancer was treated for multiple brain metastasis by gamma knife radiosurgery (GKR) in September, 2004. Two months after the initial GKR, MRI showed asymmetrical enhanced lesions involving bMCP. A few months later, MRI revealed an expansional infiltration of bMCP lesions. The patient had presented with headache loss of appetite, cerebellar ataxia, diplopia and slight dysmetria. PET showed 2-deoxy-2- [18F] fluoro-D-glucose (FDG) uptake of the bMCP lesions. The lesions were diagnosed as brain metastasis of gastric cancer. The patient underwent his second GKR (marginal dose : 19Gy, maximum dose 38Gy) MRI revealed the disappearance of the tumors 3 months after the second GKR. One year later, the patient showed no evidence of recurrence. For the last time, our case was diagnosed as brain metastasis from gastric cancer without meningeal carcinomatosis. It was suggested that FDG-PET can provide additional information about the lesion of bMCP. GKR may be useful to treat the tumor in bMCP.
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PMID:[A case of brain metastasis from gastric cancer involving bilateral middle cerebellar peduncles]. 1698 31

Doubling time (DT) is widely used for quantification of tumor growth rate. DT is usually determined from two volume estimations with measurement time intervals comparable with or shorter than DT. Clinical data show that the frequency distribution of DT in patients is positively skewed, with some very long DT values compared with the average DT. Growth rate can also be quantified using specific growth rate (SGR; %/d), equal to ln2/DT. The aim of this work was to compare DT and SGR as growth rate variables. Growth rate calculations were computer simulated for a tumor with DT of 100 days, measurement time interval of 1 to 200 days, and volume estimation uncertainty of 5% to 20%. Growth rate variables were determined and compared for previously published clinical data. The study showed that DT is not a suitable variable for tumor growth rate because (a) for short measurement time intervals, or high volume uncertainties, mean DT can either overestimate or underestimate the average growth rate; (b) DT is not defined if the consecutively estimated volumes are equal; and (c) the asymmetrical frequency distribution of DT makes it unsuitable for common statistical testing. In contrast, mean SGR and its equivalent DT give the correct values for average growth rate, SGR is defined for all tumor volume changes, and it has a symmetrical frequency distribution. SGR is also more accurate to use when discussing, for example, growth fraction, cell loss rate, and growth rate heterogeneities within the tumor. SGR should thus be used, instead of DT, to quantify tumor growth rate.
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PMID:Specific growth rate versus doubling time for quantitative characterization of tumor growth rate. 1744 Jan 13

The fungus Fusarium bulbigenum var. blasticola in which secondary tumor-like formations appear under certain conditions in aging was used as a new test system to examine the action of antitumor preparations. Free radicals in the primary mycelium and tumor-like formations without introduction of preparations (control samples) and after the introduction of preparation into the cultivation medium of the fungus have been studied by EPR spectroscopy. The EPR spectra of the fungus represent single, somewhat asymmetrical lines with a width of deltaH = 0.4 divided by 0.6 mT and g = 2.0036 +/- 0.006, which enabled one to assign the paramagnetic centers observed to melanine radicals. It was found that the concentration of free radicals in tumor-like formations is always higher than in the primary mycelium, which may be related to intensive metabolism in tumor-like formations. It has been established that several antitumor preparations (fluorouracil, hydrea, methotrexat, and vepezide) completely inhibit the growth of tumor-like formations. Another group of preparations (cyclophosphanum, dacarbazin, adriablastin, and vinblastin), on the contrary, stimulate their growth, which is accompanied by an increase in the concentration of free radicals in cells of the primary mycelium and tumor-like formations. The preparations of the third group (mercaptopurine, lanvis, and farmorubicin), despite the increased level of free radicals in cells, have a weak inhibitory effect. It has been shown that, in the concentration range studied, vitamins B2, B12, C, and PP stimulate the growth of tumor-like formations, and, when used in combination with antitumor preparations, enhance or reduce the inhibitory properties of these preparations.
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PMID:[Influence of antitumor preparations on the concentration of free radicals in cells of Fusarium bulbigenum var. blasticola fungus during primary and tumour-like secondary growth]. 1747 59

Although glioblastomas show the same histologic phenotype, biological hallmarks such as growth and differentiation properties vary considerably between individual cases. To investigate whether different subtypes of glioblastomas might originate from different cells of origin, we cultured tumor cells from 22 glioblastomas under medium conditions favoring the growth of neural and cancer stem cells (CSC). Secondary glioblastoma (n = 7)-derived cells did not show any growth in the medium used, suggesting the absence of neural stem cell-like tumor cells. In contrast, 11/15 primary glioblastomas contained a significant CD133(+) subpopulation that displayed neurosphere-like, nonadherent growth and asymmetrical cell divisions yielding cells expressing markers characteristic for all three neural lineages. Four of 15 cell lines derived from primary glioblastomas grew adherently in vitro and were driven by CD133(-) tumor cells that fulfilled stem cell criteria. Both subtypes were similarly tumorigenic in nude mice in vivo. Clinically, CD133(-) glioblastomas were characterized by a lower proliferation index, whereas glial fibrillary acidic protein staining was similar. GeneArray analysis revealed 117 genes to be differentially expressed by these two subtypes. Together, our data provide first evidence that CD133(+) CSC maintain only a subset of primary glioblastomas. The remainder stems from previously unknown CD133(-) tumor cells with apparent stem cell-like properties but distinct molecular profiles and growth characteristics in vitro and in vivo.
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PMID:CD133(+) and CD133(-) glioblastoma-derived cancer stem cells show differential growth characteristics and molecular profiles. 1748 11

Facial nerve schwannomas can occur anywhere from the internal auditory canal to the parotid gland. Schwannomas arising from the greater superficial petrosal nerve are exceedingly rare. The authors report the case of a 63-year-old woman who presented with a selective low-frequency hearing loss of 3 weeks' duration. Neurological examination demonstrated a House-Brackmann Grade II facial paresis and asymmetrical hearing loss on the left side. Audiometric evaluation showed a significant loss of low-frequency hearing with a speech reception threshold (SRT) of 30 dB and a speech discrimination score (SDS) of 88% on the left side. Magnetic resonance imaging revealed a 2.4-cm enhancing left middle fossa mass. Near-complete resection was performed via a left temporal craniotomy. The tumor was located in the Glasscock triangle and had invaded the petrous bone overlying the cochlea. A very small piece of the tumor over the cochlea was left in order to preserve hearing. A postoperative audiogram showed significant improvement in the patient's hearing, with an SRT of 20 dB and an SDS of 100%. The histological findings were consistent with schwannoma. The patient experienced postoperative improvement of hearing function despite cochlear involvement, which has previously been reported as an unfavorable factor for postoperative hearing outcome in facial nerve schwannomas.
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PMID:Recovery of low-frequency sensorineural hearing loss following resection of a greater superficial petrosal nerve schwannoma. Case report. 1763 92

Stem cells possess the capacity to expand and self-renew and do so by dividing in either a symmetrical or an asymmetrical manner. Under particular circumstances, some stem cell populations can undergo prolonged cell cycle arrest or quiescence, until they are triggered to divide by a given stimulus. In cancer treatment, these populations represent a significant roadblock to efficient therapies as their non-dividing state renders them refractory to most commonly used cytotoxic interventions. In certain organisms, germline stem cells undergo quiescence if animals experience inappropriate growth conditions, and recent studies have determined that the level of insulin signaling is key in the regulation of their proliferation rate, and that it functions through at least two tumor suppressor genes, PTEN and LKB1. These gene products regulate both growth and polarity in diverse cellular contexts, while it remains unclear how they can modulate cell division and prevent tumorigenesis through each of these functions, and whether indeed these functions are separable. We hope that understanding how these tumor suppressor genes impinge on quiescent stem cell populations could provide us with a means of designing more effective therapies to reduce the frequency of stem cell-derived tumor growth that occurs following treatment.
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PMID:Genes that affect both cell growth and polarity mediate stem cell quiescence. 1798 6

A 67-year-old man affected by moderate weight loss, acral paresthesia and plantar burning sensation was admitted to our department. Electromyographic (EMG) and electroneurographic (ENG) studies confirmed a peripheral, asymmetrical, motor-sensorial polyneuropathy (PPN). Hematological data and bone marrow biopsy discovered a non-secerning multiple myeloma (MM). All other probable causes of peripheral neuropathy could be excluded, and the possible relationship between nerve damage and neoplasia was confirmed. Furthermore, all possibilities of association of MM with PPn, namely the osteosclerotic variant, the Crow-Fukase syndrome, and the amyloid one have been evaluated. The only finding of osteolytic bone areas by radiology, the absence of organomegaly, diabetes mellitus, skin alterations, and of amyloid deposition in muscles and nerves, exclude the possible connection of the case to any of the listed possibilities. On the other hand, some clinical aspects differ, in part, to others described in the literature. In conclusion, the association between PPN and MM as the result of multiform clinical variants could be considered.
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PMID:Peripheral neuropathy and multiple myeloma in aging: a case report. 1864 92

Our objectives were 1) to characterize angiogenesis in the MDA-MB-435 xenograft mouse model with three-dimensional (3D) MR molecular imaging using alpha(5)beta(1)(RGD)- or irrelevant RGS-targeted paramagnetic nanoparticles and 2) to use MR molecular imaging to assess the antiangiogenic effectiveness of alpha(5)beta(1)(alpha(nu)beta(3))- vs. alpha(nu)beta(3)-targeted fumagillin (50 mug/kg) nanoparticles. Tumor-bearing mice were imaged with MR before and after administration of either alpha(5)beta(1)(RGD) or irrelevant RGS-paramagnetic nanoparticles. In experiment 2, mice received saline or alpha(5)beta(1)(alpha(nu)beta(3))- or alpha(nu)beta(3)-targeted fumagillin nanoparticles on days 7, 11, 15, and 19 posttumor implant. On day 22, MRI was performed using alpha(5)beta(1)(alpha(nu)beta(3))-targeted paramagnetic nanoparticles to monitor the antiangiogenic response. 3D reconstructions of alpha(5)beta(1)(RGD)-signal enhancement revealed a sparse, asymmetrical pattern of angiogenesis along the tumor periphery, which occupied <2.0% tumor surface area. alpha(5)beta(1)-targeted rhodamine nanoparticles colocalized with FITC-lectin corroborated the peripheral neovascular signal. alpha(5)beta(1)(alpha(nu)beta(3))-fumagillin nanoparticles decreased neovasculature to negligible levels relative to control; alpha(nu)beta(3)-targeted fumagillin nanoparticles were less effective (P>0.05). Reduction of angiogenesis in MDA-MB-435 tumors from low to negligible levels did not decrease tumor volume. MR molecular imaging may be useful for characterizing tumors with sparse neovasculature that are unlikely to have a reduced growth response to targeted antiangiogenic therapy.
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PMID:Three-dimensional MR mapping of angiogenesis with alpha5beta1(alpha nu beta3)-targeted theranostic nanoparticles in the MDA-MB-435 xenograft mouse model. 1869 38


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