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Find video protocols related to scientific articles indexed in Pubmed.
Antihepatoma activity of Artocarpus communis is higher in fractions with high artocarpin content.
ScientificWorldJournal
PUBLISHED: 07-14-2014
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Extracts from natural plants have been used in traditional medicine for many centuries worldwide. Artocarpus communis is one such plant that has been used to treat liver cirrhosis, hypertension, and diabetes. To our knowledge, this study is the first to investigate the antihepatoma activity of A. communis toward HepG2 and PLC/PRF/5 cells and the first to explore the relationship between antihepatoma activity and the active compound artocarpin content in different fractions of A. communis. A. communis methanol extract and fractions induced dose-dependent reduction of tumor cell viability. DNA laddering analysis revealed that A. communis extract and fractions did not induce apoptosis in HepG2 and PLC/PRF/5 cells. Instead, acridine orange staining revealed that A. communis triggered autophagic cell death in a dose-dependent manner. The antihepatoma activity of A. communis is attributable to artocarpin. The fractions with the highest artocarpin content were also the fractions with the highest antihepatoma activity in the following order: dichloromethane fraction > methanol extract > ethyl acetate fraction > n-butanol fraction > n-hexane fraction. Taken together, A. communis showed antihepatoma activity through autophagic cell death. The effect was related to artocarpin content. Artocarpin could be considered an indicator of the anticancer potential of A. communis extract.
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Mast cell leukemia: an extremely rare disease.
J Chin Med Assoc
PUBLISHED: 07-12-2014
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Systemic mastocytosis is characterized by pathologic proliferation and accumulation of mast cells in at least one extracutaneous organ such as liver, spleen, bone marrow, or lymph nodes. The clinical features are highly variable depending on impairment of the involved organ systems. It often raises diagnostic challenges. Here we report a case of a 78-year-old patient with mast cell leukemia. The literature is reviewed regarding the diagnosis and updated management of this rare disease.
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Identification of aurora kinase A as an unfavorable prognostic factor and potential treatment target for metastatic gastrointestinal stromal tumors.
Oncotarget
PUBLISHED: 06-06-2014
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Although imatinib mesylate (IM) has revolutionized the management of gastrointestinal stromal tumors (GISTs), drug resistance remains a challenge. Previous studies have shown that the expression of aurora kinase A (AURKA) predicts recurrence in patients with primary, surgically resected GISTs. The current study aimed to evaluate the significance of AURKA expression as an unfavorable prognostic marker for advanced GISTs, and provide evidence that AURKA could be a potential therapeutic target in GISTs. The prognostic significance of the expression of AURKA, along with other clinicopathological factors, was analyzed in a cohort of 99 IM-treated patients with advanced GISTs. The potential use of an inhibitor of AURKA as a therapeutic agent against GISTs was also tested in GIST cell lines. Among 99 enrolled patients, poor performance status, large tumor size, drug response, and AURKA overexpression were independent prognostic factors for poor progression-free survival (PFS). For overall survival (OS), only large tumor size and AURKA overexpression were identified as independent unfavorable factors. In an in vitro study, MLN8237, an AURKA inhibitor, inhibited growth of both IM-sensitive and IM-resistant GIST cells in a concentration-dependent manner, and exhibited synergistic cytotoxicity with IM in GIST cells. The inhibitory effect of MLN8237 in GIST cells could be attributed to the induction of G2/M arrest, apoptosis, and senescence. Our study shows that AURKA expression independently predicted poor PFS and OS in patients with advanced GISTs who were treated with IM. An AURKA inhibitor may have potential as a therapeutic agent for both IM-sensitive and IM-resistant GISTs.
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Guidelines for treating iron overload in myelodysplastic syndromes: a Taiwan consensus statement.
Int. J. Hematol.
PUBLISHED: 05-28-2014
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Iron overload is common in myelodysplastic syndrome (MDS) patients, and an accumulation of evidence shows that iron chelation may have benefits in these patients. However, discussion and consensus about iron chelation therapy (ICT) for MDS patients is lacking in Taiwan and other Southeast Asian countries. An Expert Panel in Taiwan was organized in 2011 to develop iron overload guidelines and provide a uniform reference for physicians treating MDS patients with iron overload, with specific regard to when to initiate ICT, in which patients, and the clinical and scientific rationale behind its use.
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Risk and impact of tuberculosis in patients with chronic myeloid leukemia: A nationwide population-based study in Taiwan.
Int. J. Cancer
PUBLISHED: 05-06-2014
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The relationship between chronic myeloid leukemia (CML) and tuberculosis (TB) has not been determined. We conducted a national survey including 1,082 CML patients identified from the Taiwan National Health Insurance database covering a period between 1998 and 2011; the matched non-exposed cohort included 10,820 subjects without CML that were matched for age, sex and comorbidities. The impact of TB was measured by the overall mortality, and the risk factors were identified by a multivariate Cox proportional hazards model. We found the risk of TB was higher in the CML cohort, with an adjusted hazard ratio (aHR) of 3.76 (p?=?0.001) for both pulmonary (aHR 3.23, p?
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Comparison of cetuximab to bevacizumab as the first-line bio-chemotherapy for patients with metastatic colorectal cancer: Superior progression-free survival is restricted to patients with measurable tumors and objective tumor response-a retrospective study.
J. Cancer Res. Clin. Oncol.
PUBLISHED: 03-18-2014
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We aimed to compare the treatment efficacy of cetuximab versus bevacizumab in combination with either irinotecan-based or oxaliplatin-based regimens (targeted triplet) as the first-line treatment for patients with metastatic colorectal cancer.
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Cytotoxic effects of 15d-PGJ2 against osteosarcoma through ROS-mediated AKT and cell cycle inhibition.
Oncotarget
PUBLISHED: 02-26-2014
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Polo-like kinase 1 (PLK1), a critical cell cycle regulator, has been identified as a potential target in osteosarcoma (OS). 15-deoxy-?12, 14-prostaglandin J2 (15d-PGJ2), a prostaglandin derivative, has shown its anti-tumor activity by inducing apoptosis through reactive oxygen species (ROS)-mediated inactivation of v-akt, a murine thymoma viral oncogene homolog, (AKT) in cancer cells. In the study analyzing its effects on arthritis, 15d-PGJ2 mediated shear-induced chondrocyte apoptosis via protein kinase A (PKA)-dependent regulation of PLK1. In this study, the cytotoxic effect and mechanism underlying 15d-PGJ2 effects against OS were explored using OS cell lines. 15d-PGJ2 induced significant G2/M arrest, and exerted time- and dose-dependent cytotoxic effects against all OS cell lines. Western blot analysis showed that both AKT and PKA-PLK1 were down-regulated in OS cell lines after treatment with 15d-PGJ2. In addition, transfection of constitutively active AKT or PLK1 partially rescued cells from 15d-PGJ2-induced apoptosis, suggesting crucial roles for both pathways in the anti-cancer effects of 15d-PGJ2. Moreover, ROS generation was found treatment with 15d-PGJ2, and its cytotoxic effect could be reversed with N-acetyl-l-cysteine. Furthermore, inhibition of JNK partially rescued 15d-PGJ2 cytotoxicity. Thus, ROS-mediated JNK activation may contribute to apoptosis through down-regulation of the p-Akt and PKA-PLK1 pathways. 15d-PGJ2 is a potential therapeutic agent for OS, exerting cytotoxicity mediated through both AKT and PKA-PLK1 inhibition, and these results form the basis for further analysis of its role in animal studies and clinical applications.
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Temsirolimus enhances the efficacy of cetuximab in colon cancer through a CIP2A-dependent mechanism.
J. Cancer Res. Clin. Oncol.
PUBLISHED: 01-20-2014
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A dozen clinical trials examining a combination of temsirolimus and cetuximab in treating metastatic colon cancer are currently underway. We investigated the role of cancerous inhibitor of protein phosphatase 2A (CIP2A) in the synergism between temsirolimus and cetuximab in colon cancer.
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Risk of ischemic stroke in patients with ovarian cancer: a nationwide population-based study.
BMC Med
PUBLISHED: 01-10-2014
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Cancer patients are at risk of thromboembolism. However, studies investigating the relationship between ovarian cancer and ischemic stroke are lacking. The objectives of this study were to assess the association between ovarian cancer and ischemic stroke, and to determine the predictive risk factors.
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Thymosin beta-4 knockdown in IEC-6 normal intestinal epithelial cells induces DNA re-replication via downregulating Emi1.
J. Cell. Physiol.
PUBLISHED: 01-08-2014
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Thymosin ?4 (T?4 ) is a multifunctional protein already used clinically to treat various diseases; however, the promoting effect of this protein on tumor malignancy should not be neglected. Here, we assessed whether T?4 alteration influences normal intestinal epithelial cells because T?4 is deemed a novel target for treating colorectal cancer (CRC). For this purpose, we examined the consequences of shRNA-mediated knockdown of T?4 in IEC-6 normal rat small intestinal cells and found that inhibiting T?4 expression significantly suppressed their growth and induced apoptosis in some cells. Flow cytometric analysis further revealed a marked decrease of G0/G1 population but a drastic increase of polyploid ones in these cells. The increase of polyploidy likely resulted from DNA re-replication because not only the de novo DNA synthesis was greatly increased but also the expression levels of Cdc6 (a replication-licensing factor), cyclin A, and phosphorylated-checkpoint kinase 1 were all dramatically elevated. Moreover, marked reductions in both RNA and protein levels of Emi1 (early mitotic inhibitor 1) were also detected in T?4 -downregulated IEC-6 cells which might be accounted by the downregulation of E2F1, a transcription factor capable of inducing Emi1 expression, mediated by glycogen synthase-3? (GSK-3?). To our best knowledge, this is the first report showing that inhibiting T?4 expression triggers DNA re-replication in normal intestinal epithelial cells, suggesting that this G-actin sequester may play a crucial role in maintaining genome stability in these cells. More importantly, clinical oncologists should take this novel activity into consideration when design CRC therapy based on targeting T?4 .
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Absolute lymphocyte count and risk of short-term infection in patients with immune thrombocytopenia.
Ann. Hematol.
PUBLISHED: 01-07-2014
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Patients with immune thrombocytopenia (ITP) may be at increased risk of infection because of the steroids and other immunosuppressive agents used in its treatment. This study aimed to identify events that are associated with infection within 6 months of diagnosis and the impact that infection has on survival. We retrospectively evaluated 239 patients (107 men, 132 women; median age 61 years) diagnosed between January 1997 and August 2011. Every patient received steroid treatment according to the platelet count and the extent of bleeding. Logistic regression analysis was used to identify risk factors associated with the development of infection within 6 months of ITP being diagnosed. Sixty-two patients (25.9 %) developed an infection within 6 months of diagnosis. Multivariate analysis revealed that a lower absolute lymphocyte count (ALC) at diagnosis (<1?×?10(9)/l) was an independent risk factor for infection (P?=?0.039; 95 % confidence interval, 1.033-3.599; odds ratio, 1.928). The time to infection event is significant shorter in those of low ALC, compared with those of higher ALC (P?=?0.032). Furthermore, the 1-year mortality rate after ITP diagnosis was significantly higher in those patients who developed an infection (P?=?0.001). ITP patients with a low absolute lymphocyte count at diagnosis have an increased risk of infection, and those who develop infections have lower 1-year survival.
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Effect of age and biological subtype on the risk and timing of brain metastasis in breast cancer patients.
PLoS ONE
PUBLISHED: 01-01-2014
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Brain metastasis is a major complication of breast cancer. This study aimed to analyze the effect of age and biological subtype on the risk and timing of brain metastasis in breast cancer patients.
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Randomized controlled trial of entecavir prophylaxis for rituximab-associated hepatitis B virus reactivation in patients with lymphoma and resolved hepatitis B.
J. Clin. Oncol.
PUBLISHED: 06-17-2013
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The role of antiviral prophylaxis in preventing hepatitis B virus (HBV) reactivation before rituximab-based chemotherapy in patients with lymphoma and resolved hepatitis B is unclear.
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Comparison of prognostic models for patients with diffuse large B-cell lymphoma in the rituximab era.
Ann. Hematol.
PUBLISHED: 05-25-2013
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Several revisions of International Prognostic Index (IPI) have been proposed for patients with diffuse large B-cell lymphoma (DLBCL) after the introduction of rituximab. Expanding evidence suggests that baseline absolute lymphocyte count (ALC) is also an independent factor for outcome prediction. We investigated the optimal prognostic model for these patients in the rituximab era. The study enrolled 274 consecutive patients with DLBCL receiving first-line cyclophosphamide, doxorubicin, vincristine, and prednisone based chemotherapy with rituximab between 2003 and 2009. Five factors within IPI and ALC were entered for Cox regression analysis. Overall survival (OS) and progression-free survival were calculated for different risk groups of models. Efficacy of models was compared by the value of Akaike information criterion (AIC). Revised IPI (R-IPI) and ALC/R-IPI, but not IPI, were informative to discriminate between different risk groups. In multivariate analysis for individual factors of the prognostic models, performance status >1 [odds ratio (OR) 3.59], Ann Arbor stage III or IV (OR 2.24), and ALC <1?×?10?/L (OR, 2.75) remained significant. Another modified score based on the three factors divided patients into four risk groups and the 3-year OS rate was 93, 77, 39, and 13 %, respectively. By comparing AIC values in the Cox proportional hazards model, the modified three-factor model was the superior prognostic model followed by established ALC/R-IPI, R-IPI, and standard IPI. In conclusion, the addition of the novel factor, ALC, interacts with other established factors in outcome prediction for DLBCL. Development of a new score is needed for a better risk stratification in the rituximab era and would be helpful in the design of future clinical trials. The proposed three-factor model should be validated in large-scale studies.
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Increased risk of subarachnoid hemorrhage in patients with systemic lupus erythematosus: a nationwide population-based study.
Arthritis Care Res (Hoboken)
PUBLISHED: 05-23-2013
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A relatively common occurrence of spontaneous subarachnoid hemorrhage (SAH) in patients with systemic lupus erythematosus (SLE) has been noted; however, the subsequent studies were conflicting. This nationwide population-based study aimed to evaluate the risk of SAH in patients with SLE.
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The Risk of Cancer in Patients with Benign Anal Lesions: A Nationwide Population-based Study.
Am. J. Med.
PUBLISHED: 05-17-2013
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To evaluate the risk of cancer among patients diagnosed with hemorrhoids and benign anal inflammatory lesions.
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Amiodarone and the risk of cancer: a nationwide population-based study.
Cancer
PUBLISHED: 04-08-2013
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In postmarketing surveillance, the US Food and Drug Administration has reported the development of lung masses, thyroid cancer, and skin cancer after amiodarone therapy.
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Serum albumin is an important prognostic factor for carotid blowout syndrome.
Jpn. J. Clin. Oncol.
PUBLISHED: 03-26-2013
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Carotid blowout syndrome is a severe complication of head and neck cancer. High mortality and major neurologic morbidity are associated with carotid blowout syndrome with massive bleeding. Prediction of outcomes for carotid blowout syndrome patients is important for clinicians, especially for patients with the risk of massive bleeding.
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Surface-exposed proteins of pathogenic mycobacteria and the role of cu-zn superoxide dismutase in macrophages and neutrophil survival.
Proteome Sci
PUBLISHED: 03-08-2013
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Pathogenic mycobacteria are important agents causing human disease. Mycobacterium avium subsp. hominissuis (M. avium) is a species of recalcitrant environmental pathogen. The bacterium forms robust biofilms that allow it to colonize and persist in austere environments, such as residential and commercial water systems. M. avium is also an opportunistic pathogen that is a significant source of mortality for immune-compromised individuals. Proteins exposed at the bacterial surface play a central role in mediating the relationship between the bacterium and its environment. The processes underlying both biofilm formation and pathogenesis are directly dependent on this essential subset of the bacterial proteome. Therefore, the characterization of the surface-exposed proteome is an important step towards an improved understanding of the mycobacterial biology and pathogenesis. Here we examined the complement of surface exposed proteins from Mycobacterium avium 104, a clinical isolate and reference strain of Mycobacterium avium subsp. hominissuis. To profile the surface-exposed proteins of viable M. avium 104, bacteria were covalently labeled with a membrane impermeable biotinylation reagent and labeled proteins were affinity purified via the biotin-streptavidin interaction. The results provide a helpful snapshot of the surface-exposed proteome of this frequently utilized reference strain of M. avium. A Cu-Zn SOD knockout mutant, MAV_2043, a surface identified protein, was evaluated regarding its role in the survival in both macrophages and neutrophils.
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Incidence and risk of mood disorders in patients with breast cancers in Taiwan: a nationwide population-based study.
Psychooncology
PUBLISHED: 02-11-2013
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OBJECTIVE: The objective of this study is to assess the incidence and risk of mood disorders, including major depression, anxiety, and bipolar disorders, in Taiwanese patients after the diagnosis of breast cancer compared with a matched cohort. METHODS: From January 2000 to December 2005, 26,629 newly diagnosed breast cancer patients were enrolled by the Taiwan National Health Insurance program database. The control cohort was selected randomly from 1,000,000 National Health Insurance beneficiaries from a population of 21,400,826 enrolled throughout Taiwan. Each patient was matched with one subject without breast cancer by age, sex, and presence of comorbidities with the same diagnosis index date. The diagnosis of mood disorders was defined by compatible International Classification of Diseases, 9th revision, clinical modification codes plus the prescription of antidepressants for at least 30?days. RESULTS: The overall incidence rate ratio of mood disorders was 1.33 (95% CI 1.28-1.39, p?
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Prenylated flavonoids from Artocarpus altilis: antioxidant activities and inhibitory effects on melanin production.
Phytochemistry
PUBLISHED: 01-29-2013
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Flavonoids, 10-oxoartogomezianone (1), 8-geranyl-3-(hydroxyprenyl)isoetin (2), hydroxyartoflavone A (3), isocycloartobiloxanthone (4), and furanocyclocommunin (5), together with 12 known compounds, were isolated from heartwood and cortex of Artocarpus altilis, and their structures were identified by comparing their spectra with those of similar compounds. To identify natural antioxidants and whitening agents, the ability of these prenylated flavonoids was assessed to scavenge the 1,1-diphenyl-2-picrylhydrazyl radical (DPPH), the 2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS(+·)) radical cation, and the superoxide anion (O2(-·)), and their abilities to inhibit tyrosinase and melanin production. It was found that compounds 3, 4, and artoflavone A (15) had moderate DPPH(·)-scavenging activity, whereas compound 4 exhibited significant ABTS(+·)-scavenging activity, and that norartocarpetin (7) and artogomezianone (8) exhibited moderate ABTS(+·)-scavenging activity, with compounds 2, 7, and artocarpin (6) displaying good superoxide anion-scavenging activity. In addition, compounds 7, 8, cudraflavone A (14), and artonin M (17), inhibited melanin production by strongly suppressing tyrosinase activity. Compound 6 reduced the melanin content without inhibiting tyrosinase activity. These results suggest that flavonoids isolated from A. altilis may be candidate antioxidants and/or skin-whitening agents. However, further investigations are required to determine their mechanisms of action.
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Absolute lymphocyte count predicts response to rituximab-containing salvage treatment for relapsed/refractory B-cell non-Hodgkins lymphoma with prior rituximab exposure.
J Chin Med Assoc
PUBLISHED: 01-23-2013
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Rituximab-containing salvage chemotherapy has shown promising efficacy in patients with relapsed/refractory B-cell non-Hodgkins lymphoma (NHL). The aim of this study was to examine the efficacy of rituximab-containing treatment in patients with B-cell NHL who developed relapsed or refractory disease after prior rituximab use and to explore the predictive factors of response using this approach.
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The risk of cancer in patients with generalized anxiety disorder: a nationwide population-based study.
PLoS ONE
PUBLISHED: 01-18-2013
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To evaluate the risk of cancer among patients with generalized anxiety disorder (GAD) in a nationwide population-based dataset.
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Differences in high on-treatment platelet reactivity between intra-coronary and peripheral blood after dual anti-platelet agents in patients with coronary artery disease.
Thromb. Haemost.
PUBLISHED: 01-13-2013
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The differences of high on-treatment platelet reactivity (HPR) between the coronary arteries and peripheral veins might be associated with poor prediction of adverse cardiovascular events in patients with coronary artery diseases. HPR from the peripheral blood might not adequately reflect the platelet responses in the coronary artery. A total of 21 patients were recruited, and regional differences in HPR were compared between blood samples from the intra-coronary artery (IC), femoral artery (FA), and femoral vein (FV) by light aggregometry (agonists: arachidonic acid, LTA-AA; ADP, LTA-ADP), VerifyNow P2Y12 assays, and a platelet function analyser (PFA-100, collagen and epinephrine cartridge, PFA-CEPI). There were regional differences in the platelet reactivities observed by LTA-AA, VerifyNow P2Y12 assays, and PFA-CEPI. Platelets from the IC had higher platelet reactivities than those from the FV and FA by the VerifyNow P2Y12 assays but lower reactivities by LTA-AA and PFA-CEPI. HPR values from the blood in the FA were more similar to those from the IC than those from the FV by any test. The monocyte percentages were the only factors associated with differences in HPR between the FV and IC by the VerifyNow P2Y12 assays. Triglyceride levels were associated with the differences in HPR between the FV and IC by LTA-ADP. During the six-month follow-up period, two patients developed cardiovascular events and exhibited differences in HPR between different sites by VerifyNow P2Y12 assays. In conclusions, there were regional differences in HPR in patients with coronary artery diseases, which might prevent the adequate prediction of cardiovascular events.
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Diminishing prognostic role of preexisting diabetes mellitus for patients with diffuse large B-cell lymphoma in the rituximab era.
Ann. Hematol.
PUBLISHED: 01-05-2013
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Rituximab reforms the treatment of diffuse large B-cell lymphoma (DLBCL) and the prognostic significance of baseline patient features should be reevaluated. Few population-based studies have investigated the association of diabetes mellitus (DM) and outcomes of lymphoma; however, the results remain inconclusive. From January 1, 2000 to December 31, 2009, a total of 468 consecutive newly diagnosed DLBCL patients receiving first-line chemotherapy with cyclophosphamide, vincristine, doxorubicin, and prednisolone (CHOP) or rituximab plus CHOP (R-CHOP) were enrolled. Pre-existing DM was defined according to medical history, use of antidiabetic medications, or any record of an abnormal hemoglobin A1c test. Progression-free survival (PFS) and overall survival (OS) were estimated and compared using the Kaplan-Meier method with a log-rank test. CHOP was administered in 194 patients, and 274 patients received R-CHOP. DM was identified in 16.2 % (76/468) of patients. Diabetic patients were older and more performance restricted, compared to the non-DM patients in both the CHOP and R-CHOP groups. In the CHOP group, 5-year PFS and OS were inferior in DM patients (PFS, 32.4 vs. 50.0 % (P?=?0.039); OS, 38.2 vs. 62.5 % (P?=?0.002)). However, outcomes were similar for both DM and non-DM patients in the context of R-CHOP treatment (PFS, 69.0 vs. 57.3 % (P?=?0.179); OS, 76.2 vs. 69.8 % (P?=?0.586)). The response rate of chemotherapy in DM patients was also improved to a level similar to non-DM patients with rituximab use. In conclusion, the prognostic significance of preexisting DM in DLBCL patients is changing in the rituximab era. The potentially additional benefit of rituximab in DM patients merits further investigation.
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Leukocytosis in polycythemia vera and splenomegaly in essential thrombocythemia are independent risk factors for hemorrhage.
Eur. J. Haematol.
PUBLISHED: 01-04-2013
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Long-term outcomes are favorable for patients with polycythemia vera (PV) and for patients with essential thrombocythemia (ET). However, hemorrhage is a significant cause of morbidity and mortality in those patients.
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the risk of cancer among Taiwanese female registered nurses: a nationwide retrospective study.
PLoS ONE
PUBLISHED: 01-01-2013
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To evaluate the risk of cancer among Taiwanese female registered nurses (RNs) using a nationwide population-based dataset.
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Chronic kidney disease stage 5 as the prognostic complement of International Staging System for multiple myeloma.
Eur. J. Haematol.
PUBLISHED: 11-17-2011
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Reversal of renal impairment (RI) in patients with multiple myeloma (MM) has been evaluated using the estimated glomerular filtration rate (eGFR(MDRD) ) formula developed by the Modification of Diet in Renal Disease study group. However, the prognostic impact of eGFR(MDRD) at diagnosis of MM is not well studied, particularly its use in conjunction with the International Staging System (ISS).
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Clinicopathologic features and outcome of acute erythroid leukemia based on 2008 revised World Health Organization classification.
Leuk. Lymphoma
PUBLISHED: 09-23-2011
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We report 67 patients with acute erythroid leukemia (erythroleukemia) based on the World Health Organization (WHO) 2008 classification. Reviewing the clinicopathologic features, cytogenetics and outcomes, the characteristics of erythroleukemia resembled myelodysplastic syndromes (MDS). Patients with poor performance status, advanced anemia and poor-risk cytogenetics had significantly inferior outcomes. The International Prognostic Scoring System (IPSS) for MDS is useful to differentiate the prognosis of erythroleukemia.
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The efficacy of chemotherapy in patients with high-grade metastatic colon cancer.
Hepatogastroenterology
PUBLISHED: 07-15-2011
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This study was undertaken to assess the prognostic role of histological grade in colon cancer and the efficacy of either oxaliplatin or irinotecan after incorporation into an infusional regimen of 5-fluorouracil and leucovorin in patients with high-grade metastatic colon cancer.
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A new classification scheme for recurrent or metastatic colon cancer after liver metastasectomy.
J Chin Med Assoc
PUBLISHED: 07-05-2011
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Metastasectomy is the standard treatment for patients with resectable liver metastasis from colon cancer. This study aimed to determine the impact of initial stage on overall survival (OS) after metastasectomy.
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Pyogenic liver abscess as the initial manifestation of underlying hepatocellular carcinoma.
Am. J. Med.
PUBLISHED: 06-23-2011
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Pyogenic liver abscess and hepatocellular carcinoma are common in Taiwan. We investigated the frequency of, risk factors for, and prognosis of pyogenic liver abscess as the initial manifestation of underlying hepatocellular carcinoma over a 12-year period in Taiwan.
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A freshwater cyanophage whose genome indicates close relationships to photosynthetic marine cyanomyophages.
Environ. Microbiol.
PUBLISHED: 05-23-2011
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Bacteriophage S-CRM01 has been isolated from a freshwater strain of Synechococcus and shown to be present in the upper Klamath River valley in northern California and Oregon. The genome of this lytic T4-like phage has a 178,563 bp circular genetic map with 297 predicted protein-coding genes and 33 tRNA genes that represent all 20-amino-acid specificities. Analyses based on gene sequence and gene content indicate a close phylogenetic relationship to the photosynthetic marine cyanomyophages infecting Synechococcus and Prochlorococcus. Such relatedness suggests that freshwater and marine phages can draw on a common gene pool. The genome can be considered as being comprised of three regions. Region 1 is populated predominantly with structural genes, recognized as such by homology to other T4-like phages and by identification in a proteomic analysis of purified virions. Region 2 contains most of the genes with roles in replication, recombination, nucleotide metabolism and regulation of gene expression, as well as 5 of the 6 signature genes of the photosynthetic cyanomyophages (hli03, hsp20, mazG, phoH and psbA; cobS is present in Region 3). Much of Regions 1 and 2 are syntenic with marine cyanomyophage genomes, except that a segment encompassing Region 2 is inverted. Region 3 contains a high proportion (85%) of genes that are unique to S-CRM01, as well as most of the tRNA genes. Regions 1 and 2 contain many predicted late promoters, with a combination of CTAAATA and ATAAATA core sequences. Two predicted genes that are unusual in phage genomes are homologues of cellular spoT and nusG.
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Effective salvage therapy of imatinib-resistant gastrointestinal stromal tumor with combination of imatinib and pegylated liposomal doxorubicin.
J Chin Med Assoc
PUBLISHED: 05-13-2011
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Here we presented a 60-year-old Taiwanese man with advanced gastrointestinal stromal tumor. Disease progression was noted during imatinib treatment. Surgical resection was done and mutation analysis of KIT gene in all the resected tumors revealed deletion mutations of codons 558-565 in exon 11, whereas a missense mutation was also identified at codon 822 in exon 17 in one resected tumor. Patients disease was refractory to escalating dose of imatinib and dasatinb. Surprisingly, combination of imatinib with pegylated liposomal doxorubicin produced a substantial response and resulted in a 5-month progression free period for this imatinib-resistant gastrointestinal stromal tumor.
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Chronic hepatitis virus infection in patients with multiple myeloma: clinical characteristics and outcomes.
Clinics (Sao Paulo)
PUBLISHED: 05-10-2011
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Cytotoxic agents and steroids are used to treat lymphoid malignancies, but these compounds may exacerbate chronic viral hepatitis. For patients with multiple myeloma, the impact of preexisting hepatitis virus infection is unclear. The aim of this study is to explore the characteristics and outcomes of myeloma patients with chronic hepatitis virus infection.
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Nosocomial Klebsiella pneumoniae bacteraemia in adult cancer patients--characteristics of neutropenic and non-neutropenic patients.
Scand. J. Infect. Dis.
PUBLISHED: 05-04-2011
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Neoplastic diseases are common in patients with nosocomial Klebsiella pneumoniae bacteraemia. This study investigated the clinical characteristics of neutropenic and non-neutropenic adult cancer patients with nosocomial K. pneumoniae bacteraemia.
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Enhancement of dissolution and antioxidant activity of kaempferol using a nanoparticle engineering process.
J. Agric. Food Chem.
PUBLISHED: 03-25-2011
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Kaempferol (KAE) is a strong antioxidant flavonoid compound, but its clinical application is limited by quantity and poor dissolution property. However, the dissolution mechanism of a kaempferol nanoparticle formulation (KAEN) has not yet been elucidated. The aim of the present study was therefore to use a nanoparticle engineering process to resolve the dissolution problem. Our data indicated that KAEN effectively increased the dissolution percentage by particle size reduction, high encapsulation efficiency, amorphous transformation, and hydrogen-bond formation with excipients. In addition, we used several different antioxidant activity assays to evaluate KAE and KAEN. The data indicated that KAEN retained potent antioxidant activity after the nanoparticle engineering process and showed better antioxidant activity than KAE dissolved in water (P < 0.05). According to these findings, we concluded that KAEN could be a low-dose alternative to KAE in health food and future clinical research.
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Brain, the last fortress of sarcoma: similar dismal outcome but discrepancy of timing of brain metastasis in bone and soft tissue sarcoma.
J Surg Oncol
PUBLISHED: 03-16-2011
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Brain metastasis is a rare but dismal event in sarcomas. However, the pattern of occurrence and the prognostic factors associated with post-brain metastasis survival (PBMS) are not yet well-characterized.
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Low absolute lymphocyte count and addition of rituximab confer high risk for interstitial pneumonia in patients with diffuse large B-cell lymphoma.
Ann. Hematol.
PUBLISHED: 03-09-2011
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Several small-scale studies have reported pulmonary toxicity among patients with diffuse large B-cell lymphoma (DLBCL) receiving rituximab-containing chemotherapy, though whether the use of rituximab predisposes to interstitial pneumonia (IP) remains unclear. This retrospective study was intended to identify the characteristics and risk factors of IP in patients with DLBCL. Between 2000 and 2009, 529 consecutive patients with DLBCL receiving first-line tri-weekly COP- or CHOP-based chemotherapy with or without rituximab were enrolled as subjects. IP was defined as diffuse pulmonary interstitial infiltrates found on computed tomography scans in conjunction with respiratory symptoms. IP was observed in 26 patients (4.9%), six of whom were confirmed with Pneumocystis jirovecii pneumonia. The median number of chemotherapy courses before IP was four cycles. Using multivariate analysis, absolute lymphocyte count less than 1×10(9)/l at diagnosis [odds ratio (OR) 2.75, p=0.014] and the addition of rituximab to chemotherapy (OR 4.56, p=0.003) were identified as independent risk factors for IP. In conclusion, the incidence of IP is increased in patients with DLBCL receiving rituximab-containing chemotherapy. Specific subgroups with lymphopenia at diagnosis may justify close scrutiny to detect pulmonary complications.
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International Staging System predicts prognosis of Chinese patients with multiple myeloma across different calendar periods with application of novel agents.
Ann. Hematol.
PUBLISHED: 03-08-2011
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The applicability of the International Staging System (ISS) for Chinese patients with multiple myeloma (MM) has not been demonstrated, especially with respect to treatments with novel agents. Newly diagnosed MM patients at Taipei Veterans General Hospital were enrolled between 1996 and 2007. Data regarding clinical features, laboratory tests, and outcome at last follow-up were collected. A total of 389 MM patients (71% male) were enrolled, with median age of 71 years. At diagnosis, 72.7% had Durie-Salmon (DS) stage III disease, 56.2% had ISS stage III disease, and 34% had serum creatinine ?2.0 mg/dL. Compared with patients diagnosed in the first calendar period 1996-2001, the patients of the second calendar period 2002-2007 were older and more of these patients had received novel agents, especially thalidomide. The median overall survival period was 20.5 months, with a significant increase of patients in the second calendar period (15.3 and 28.2 months, respectively; P?=?0.002), especially for those with ISS stages I and II. In the Cox proportion model, elevated serum ?(2) microglobulin at diagnosis (?3.5 mg/L), old age (?65 years), and impaired renal function were found to be independently associated with poor survival. Over the entire period, the ISS was found to be effective in providing an accurate prognosis with respect to different ages and calendar periods. This is the first study to show the applicability of ISS for Chinese patients with MM, especially for those who had received thalidomide.
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Liver abscess after liver metastasectomy is a poor prognostic factor in patients with colorectal cancer.
J. Gastrointest. Surg.
PUBLISHED: 03-06-2011
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More and more complications of extensive hepatic resection are being encountered in patients treated for liver metastases from colorectal cancer. This study aimed to determine the impact of liver abscess after hepatic resection on overall survival (OS) and the role of adjuvant chemotherapy.
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Duloxetine improves oxaliplatin-induced neuropathy in patients with colorectal cancer: an open-label pilot study.
Support Care Cancer
PUBLISHED: 02-04-2011
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This open-label pilot study is aimed to evaluate the efficacy and tolerability of the antidepressant duloxetine, which is effective for diabetic neuropathic pain, in the treatment of chronic oxaliplatin-induced peripheral neuropathy (OIPN).
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A study using ifosfamide and etoposide in patients with cisplatin-refractory recurrent or metastatic head and neck squamous cell carcinoma.
Jpn. J. Clin. Oncol.
PUBLISHED: 02-04-2011
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To investigate the efficacy and safety of combination therapy with ifosfamide and etoposide in cisplatin-refractory recurrent/metastatic squamous cell carcinoma of the head and neck.
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Triweekly reduced-dose docetaxel combined with cisplatin in recurrent/metastatic head and neck squamous cell carcinoma: a multicenter phase II study.
Cancer Chemother. Pharmacol.
PUBLISHED: 01-29-2011
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To test the efficacy and safety of a triweekly reduced-dose docetaxel (60 mg/m(2)) regimen combined with a standard dose of cisplatin in patients with recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC).
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Prevalence and prognostic influence of genomic changes of EGFR pathway markers in synovial sarcoma.
J Surg Oncol
PUBLISHED: 01-15-2011
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We aimed to study the prevalence and prognostic influence of epidermal growth factor receptor (EGFR) and its downstream effectors in synovial sarcoma (SS).
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PML protein as a prognostic molecular marker for patients with esophageal squamous cell carcinomas receiving primary surgery.
J Surg Oncol
PUBLISHED: 01-15-2011
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We evaluated the clinicopathological associations and prognostic implications of promyelocytic leukemia gene (PML) expressions in patients with esophageal squamous cell carcinomas (ESCC) receiving primary surgery.
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Pretreatment risk stratification for non-metastatic head and neck squamous cell carcinoma in a high-prevalence area.
J Chin Med Assoc
PUBLISHED: 01-12-2011
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This retrospective study was to establish a prognostic scoring system for patients with non-metastatic head and neck squamous cell carcinoma (HNSCC).
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Effect of allogeneic hematopoietic stem cell transplantation from matched siblings or unrelated donors during the first complete remission in patients with cytogenetically normal acute myeloid leukemia.
Eur. J. Haematol.
PUBLISHED: 01-11-2011
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We retrospectively examined the impact of hematopoietic stem cell transplantation (HSCT) during the first complete remission (CR1) in 81 patients with cytogenetically normal acute myeloid leukemia (CN-AML). Eligible patients were divided into three subgroups: HSCT recipients with allogeneic sibling or matched unrelated donors (MUD) (allogeneic HSCT, n = 47), recipients of autologous HSCT (n = 12), and patients receiving chemotherapy alone (n = 22). We examined factors associated with overall survival (OS) in these patients, focusing particularly on the effect of allogeneic HSCT. Comparing to those receiving chemotherapy alone, patients in the allogeneic HSCT group had significantly better OS, which was independent of the presence of comorbidities. Furthermore, patients who received allogeneic sibling HSCT had the best OS and disease-free survival (DFS). Patients who received MUD HSCT also had significant advantage in DFS but not in OS, when compared with patients in the chemotherapy group. The study results suggest that patients with CN-AML in CR1 who are eligible for HSCT may have a survival benefit from HSCT, especially the allogeneic HSCT. We suggest that future studies employ molecular classification of AML to better define the benefits of HSCT during CR1 in patients with CN-AML.
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Impact of circulating monocyte CD36 level on atrial fibrillation and subsequent catheter ablation.
Heart Rhythm
PUBLISHED: 11-13-2010
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Inflammation, an important mechanism in the pathogenesis of atrial fibrillation (AF), can be regulated by CD36 in monocytes.
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Clinical features and prognostic factors of angioimmunoblastic T-cell lymphoma in Taiwan: a single-institution experience.
Leuk. Lymphoma
PUBLISHED: 11-05-2010
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Angioimmunoblastic T-cell lymphoma (AITL) is a rare subtype of peripheral T-cell lymphoma that carries a poor prognosis. This study retrospectively analyzed patients with AITL from a single institution in Taiwan, aiming to define the clinical features and prognostic factors. Patients with AITL treated at our institution from February 1988 through January 2010 were enrolled. Factors associated with overall survival (OS) were determined by statistical methods. A total of 31 Taiwanese patients (21 males) were identified. The median age was 74 years (range, 27-90). Among all patients, 67.7% were Ann Arbor stage III or IV, 58.1% presented with B symptoms, 48.4% had hypoalbuminenia (<35 g/L), and 63.3% had elevated lactate dehydrogenase (LDH) at diagnosis. First-line chemotherapy was mostly CHOP (cyclophosphamide, vincristine, doxorubicin, and prednisolone)-based and complete response (CR) was achieved in 25% of patients. The actuarial 2-year survival rate was 38.7%, and the median OS was 14.9 months. In multivariate analysis, initial presentation with fever (p?=?0.035), advanced stage (p?=?0.024), and failure to achieve CR (p?=?0.029) were independent adverse factors associated with poorer OS. Interestingly, OS did not differ whether chemotherapy regimens contained anthracycline or not. Taiwanese patients with AITL were usually elderly. Despite the prognosis being generally poor, patients with AITL should be treated with the goal of achieving CR, regardless of anthracycline- or non-anthracycline-based chemotherapy.
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Pneumothorax after bevacizumab-containing chemotherapy: a case report.
Jpn. J. Clin. Oncol.
PUBLISHED: 10-28-2010
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Bevacizumab added to 5-fluorouracil-based chemotherapy can improve outcomes in patients with metastatic colorectal cancer. Bevacizumab had several notable adverse effects including bowel perforation but pneumothorax had never been reported in the available English literature. We reported a 45-year-old male with lung metastases from colorectal cancer who had spontaneous pneumothorax after the second cycle of bevacizumab-containing chemotherapy. His pneumothorax resolved after tube thoracostomy with a small caliber catheter. The mechanism of pneumothorax developed after bevacizumab therapy was not clear as bowel perforation but tumor necrosis with ruptured parietal pleura might be the cause. In patients who had chest discomfort after bevacizumab-containing therapy, pneumothorax should never be overlooked as one of the differential diagnoses.
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Sudden-onset pancytopenia with intracranial hemorrhage after oxaliplatin treatment: a case report and literature review.
Jpn. J. Clin. Oncol.
PUBLISHED: 09-07-2010
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Oxaliplatin is a third-generation platinum compound and has been widely employed in the treatment of colorectal cancer. Despite its good efficacy, it is reported to induce immune-mediated cytopenia. We report the case of a 78-year-old male patient who experienced acute pancytopenia along with coagulopathy and intracranial hemorrhage after his 17th course of oxaliplatin. This condition appeared immediately after completion of oxaliplatin infusion, and was persistent despite aggressive transfusion and treatment with granulocyte colony-stimulating factor. The patient died 72 h after the administration of oxaliplatin. The only preceding symptom was chills 30 min after initiation of oxaliplatin, although steroid was given as premedication. We review the literature describing oxaliplatin-induced cytopenia, and discuss the manifestation, immune mechanism and treatment of this condition. We conclude that any symptoms that occur during infusion of oxaliplatin should not be overlooked but should be taken seriously as they may represent a little spark that kindles a great fire, and that steroids may provide an effective treatment for oxaliplatin-induced cytopenia. However, a major complication in our patient may still happen. Further studies for the mechanism and the predictive markers of oxaliplatin-induced cytopenia are worthy.
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Regulation of excision repair cross-complementation group 1 by Snail contributes to cisplatin resistance in head and neck cancer.
Clin. Cancer Res.
PUBLISHED: 09-07-2010
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We investigated the mechanism and clinical significance of the epithelial-mesenchymal transition (EMT)-induced chemoresistance in head and neck squamous cell carcinoma (HNSCC).
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Bmi1 is essential in Twist1-induced epithelial-mesenchymal transition.
Nat. Cell Biol.
PUBLISHED: 08-04-2010
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The epithelial-mesenchymal transition (EMT), one of the main mechanisms underlying development of cancer metastasis, induces stem-like properties in epithelial cells. Bmi1 is a polycomb-group protein that maintains self-renewal, and is frequently overexpressed in human cancers. Here, we show the direct regulation of BMI1 by the EMT regulator, Twist1. Furthermore, Twist1 and Bmi1 were mutually essential to promote EMT and tumour-initiating capability. Twist1 and Bmi1 act cooperatively to repress expression of both E-cadherin and p16INK4a. In patients with head and neck cancers, increased levels of both Twist1 and Bmi1 correlated with downregulation of E-cadherin and p16INK4a, and was associated with the worst prognosis. These results suggest that Twist1-induced EMT and tumour-initiating capability in cancer cells occurs through chromatin remodelling, which leads to unfavourable clinical outcomes.
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Cetuximab-based therapy in recurrent/metastatic head and neck squamous cell carcinoma: experience from an area in which betel nut chewing is popular.
J Chin Med Assoc
PUBLISHED: 05-31-2010
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This study was undertaken to evaluate the efficacy and safety of cetuximab-based therapy in recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) in an area in which betel nut chewing is popular.
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Curcumin nanoparticles improve the physicochemical properties of curcumin and effectively enhance its antioxidant and antihepatoma activities.
J. Agric. Food Chem.
PUBLISHED: 05-22-2010
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Curcumin (CUR), a natural polyphenol isolated from tumeric ( Curcuma longa ), has been documented to possess antioxidant and anticancer activities. Unfortunately, the compound has poor aqueous solubility, which results in poor bioavailability following high doses by oral administration. To improve the solubility of CUR, we developed a novel curcumin nanoparticle system (CURN) and investigated its physicochemical properties as well as its enhanced dissolution mechanism. Our results indicated that CURN improved the physicochemical properties of CUR, including a reduction in particle size and the formation of an amorphous state with hydrogen bonding, both of which increased the drug release of the compound. Moreover, in vitro studies indicated that CURN significantly enhanced the antioxidant and antihepatoma activities of CUR (P < 0.05). Consequently, we suggest that CURN can be used to reduce the dosage of CUR and improve its bioavailability and merits further investigation for therapeutic applications.
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Systemic amyloidosis manifesting as a rare cause of hepatic failure.
J Chin Med Assoc
PUBLISHED: 03-17-2010
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In 1854, the term "amyloid" was first used in the description of a liver specimen at autopsy by Virchow. The kidneys and heart are the most commonly involved organs in amyloidosis; liver and gastrointestinal tract involvement is less common, and the symptoms are usually mild. Here, we report the case of a 57-year-old male patient who presented with oral hemorrhagic bullae, thrombocytopenia and jaundice. Disseminated intravascular coagulation profile was positive. Abdominal sonography showed ascites, and abdominal computed tomography disclosed heterogeneous enhancement of the liver, with focal low attenuation regions and splenomegaly with poor contrast enhancement. Liver decompensation was highly suspected. Diagnostic laparoscopy with liver biopsy and colonoscopic biopsy from the rectum were subsequently performed. Typical apple-green birefringence was demonstrated on polarized light microscopy by Congo red staining. Systemic amyloidosis was diagnosed and colchicine prescribed. However, liver function deteriorated and intermittent gastrointestinal bleeding was found during the patients hospitalization. The patient died due to uncorrectable coagulopathy and massive gastrointestinal bleeding. The final diagnosis was idiopathic amyloidosis with hepatic failure. Although amyloidosis rarely presents with hepatic failure, it should be considered in patients with signs of liver decompensation. Clinicians should be aware of this rare but potentially lethal presentation and arrange appropriate treatment promptly.
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Soft tissue sarcoma of extremities: the prognostic significance of adequate surgical margins in primary operation and reoperation after recurrence.
Ann. Surg. Oncol.
PUBLISHED: 03-09-2010
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Adult soft tissue sarcomas (STS) of extremities are prone to recurrence despite apparently complete resection. This study aimed to explore the impact of clinicopathological factors on outcome and to define an "oncological safe margin" in these patients.
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Severe extensive bone marrow necrosis from miliary tuberculosis without granulomas and pulmonary presentations.
J Chin Med Assoc
PUBLISHED: 01-28-2010
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Bone marrow necrosis (BMN) is a rare clinicopathologic entity caused by hypoxemia after failure of the microcirculation, which frequently manifests with bone pain, fever, and peripheral cytopenia. In most reported cases of BMN resulting from miliary tuberculosis (TB), the presence of marrow granulomas, pulmonary infiltrates and/or extrapulmonary involvement is common. We report a female patient with extensive BMN from miliary TB, whose initial presentation was only severe peripheral cytopenia with extensive marrow necrosis, with neither evident pulmonary manifestations nor granulomas in the marrow biopsy. Serial Ziehl-Neelsen stains and Mycobacterium tuberculosis cultures were negative. The diagnosis of suspected miliary TB was made by consecutive positive results from polymerase chain reaction analysis for TB of marrow samples at 2 separate examination time points and a good treatment response to anti-TB therapy. Magnetic resonance imaging showed a geographic pattern of multiple signal abnormalities, indicating bone infarcts over the bilateral iliac bones and T-L-spine vertebral bodies, compatible with extensive BMN. The unusual presentation of extensive BMN with severe peripheral cytopenia in the absence of granulomas or pulmonary presentations should alert clinical physicians in epidemic areas. We discuss the use of polymerase chain reaction analysis for TB and magnetic resonance imaging for diagnosis of these patients.
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Macroenzyme creatine kinase in the era of modern laboratory medicine.
J Chin Med Assoc
PUBLISHED: 01-28-2010
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Among the conditions in which creatine kinase (CK)-MB activity is elevated in the absence of myocardial injury or infarction, macroenzyme (macro) CK merits special attention from clinicians. We present 2 cases, 1 with macro CK type 1 and the other with macro CK type 2, to stress the common clinical situations and diagnostic dilemma that clinicians encounter when evaluating patients with macro CK. Moreover, the rare conditions associated with macro CK, and the phenomenon of spuriously high CK-MB activity out of proportion to total CK, are discussed. The biochemical characteristics, clinical significance and potential implications of macro CK are reviewed within the scope of modern laboratory medicine.
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Phosphorylation status of transcription factor C/EBPalpha determines cell-surface poly-LacNAc branching (I antigen) formation in erythropoiesis and granulopoiesis.
Blood
PUBLISHED: 01-25-2010
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The cell-surface straight and branched repeats of N-acetyllactosamine (LacNAc) units, called poly-LacNAc chains, characterize the histo-blood group i and I antigens, respectively. The transition of straight to branched poly-LacNAc chain (i to I) is determined by the I locus, which expresses 3 IGnT transcripts, IGnTA, IGnTB, and IGnTC. Our previous investigation demonstrated that the i-to-I transition in erythroid differentiation is regulated by the transcription factor CCAAT/enhancer binding protein alpha (C/EBPalpha). In the present investigation, the K-562 cell line was used as a model to show that the i-to-I transition is determined by the phosphorylation status of the C/EBPalpha Ser-21 residue, with dephosphorylated C/EBPalpha Ser-21 stimulating the transcription of the IGnTC gene, consequently resulting in I branching. Results from studies using adult erythropoietic and granulopoietic progenitor cells agreed with those derived using the K-562 cell model, with lentiviral expression of C/EBPalpha in CD34(+) hematopoietic cells demonstrating that the dephosphorylated form of C/EBPalpha Ser-21 induced the expression of I antigen, granulocytic CD15, and also erythroid CD71 antigens. Taken together, these results demonstrate that the regulation of poly-LacNAc branching (I antigen) formation in erythropoiesis and granulopoiesis share a common mechanism, with dephosphorylation of the Ser-21 residue on C/EBPalpha playing the critical role.
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A patient of situs ambiguus with pancreatic head cancer successfully treated with gemcitabine and erlotinib.
Med. Oncol.
PUBLISHED: 01-06-2010
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We report a case of a 66-year-old Taiwanese female patient with situs ambiguus diagnosed of pancreatic head cancer. She was treated with gemcitabine and erlotinib and remained in stable disease on follow-up imaging studies. Situs ambiguus is a rare disease and reports of such patients with cancer have rarely been reported in the literature. Our case illustrates that standard chemotherapy in this group of patients may be undergone with promising results.
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Identification of increased NBS1 expression as a prognostic marker of squamous cell carcinoma of the oral cavity.
Cancer Sci.
PUBLISHED: 12-15-2009
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Oral squamous cell carcinoma (OSCC) is one of the most prevalent cancers worldwide; however, accurate molecular markers to predict its prognosis are still limited. We previously demonstrated that overexpression of the DNA double-strand break repair protein NBS1 is a prognostic marker of advanced head and neck squamous cell carcinoma (HNSCC). Therefore, we aimed to investigate the feasibility of using NBS1 as a biomarker in OSCC. In this study, we enrolled 148 OSCC for immunohistochemical (IHC) and clinical analysis. Data from 58 advanced non-oral-cavity HNSCC (NO-HNSCC) cases were also included for comparison due to the biological and clinical discrepancy between OSCC and HNSCC originated from the other sites (e.g. pharynx or larynx). First, we validated the NBS1 IHC results by real-time RT-PCR analysis, and an excellent correlation between the results of these two assays confirmed the reliability and robustness of IHC procedures and interpretation. NBS1 overexpression was an independent prognostic marker in both OSCC and NO-HNSCC cases. In OSCC, the prognostic significance of NBS1 was shown regardless of T stage and lymph node status. Increased NBS1 expression correlated with advanced T stage and recurrence/metastasis. NBS1 overexpression correlated with the phosphorylation levels of Akt and its downstream target mammalian target of rapamycin (mTOR). These results clearly illustrate the expression profile of NBS1 in OSCC and NO-HNSCC, and highlight the role of NBS1 in HNSCC irrespective of the primary sites. It also indicates the practicability of application of NBS1 as a marker in OSCC.
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Influence of GSTP1 I105V polymorphism on cumulative neuropathy and outcome of FOLFOX-4 treatment in Asian patients with colorectal carcinoma.
Cancer Sci.
PUBLISHED: 10-28-2009
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Glutathione S-transferase P1 (GSTP1) participates in detoxification of potentially genotoxic compounds that may alter the efficacy and toxicity of platinum-based chemotherapy. We analyzed the influence of I105V polymorphism of GSTP1 on clinico-pathological features and outcomes in 166 Chinese patients with metastatic colorectal carcinoma who had been treated with first-line FOLFOX-4. Combined analysis of GSTP1 I105V, ERCC1-118, and XPD-751 polymorphisms was also conducted. The results showed that, in comparison with Caucasian populations, a remarkably lower prevalence of Val105 allele variants was noted (24.7%). Patients with Val105 allele variants had a higher response to FOLFOX-4 (56.1%vs 37.6%, P = 0.04), and a longer progression-free (P < 0.01) as well as overall (P < 0.01) survival. By adjusted analysis, this polymorphism was identified as an independent prognostic factor (P = 0.01). In combined analysis, patients without any risk genotype, including GSTP1-105 Ile/Ile, ERCC1-118 C/T or T/T, and XPD-751 Lys/Gln, had significantly longer progression-free and overall survivals (P < 0.01). In addition, patients with Val105 allele variants had a higher incidence of grade 3/4 cumulative neuropathy after different cycles of treatment. These data suggest that Asian populations have a lower prevalence of I105V polymorphism in GSTP1. I105V polymorphism in GSTP1, by reducing its enzymatic activity and consequential detoxification to oxaliplatin, could be a key determinant for a better outcome, but more neurotoxicity, to FOLFOX-4 treatment.
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Identification of chromosomal aberrations associated with disease progression and a novel 3q13.31 deletion involving LSAMP gene in osteosarcoma.
Int. J. Oncol.
PUBLISHED: 09-03-2009
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Five osteosarcoma (OS) cell lines, 37 OS tumors and 9 corresponding non-neoplastic samples were genotyped by Affymetrix 10 K 2.0 SNP array. Regions of high level amplification and homozygous deletion were identified and validated by quantitative PCR and FISH. Certain recurrent cytogenetic alterations were more frequent in recurrent/metastatic than in primary OS. These included deletion of 6q14.1, 6q16.2-q22.31, and 8p23.2-p12, amplification of 8q21.12, 8q22.3-q24.3 and 17p12, and loss of heterozygosity (LOH) at 2q24.3-q31.2, 5q11.2, 6p21.31-p21.1, 6q14.1-q16.2, 8p22-p12, 9q22.1, 10q21.1-q22.1, 10q23.31-q24.1, 12q15-q21.1 and 21q21.2-q21.3. Most of the LOH calls were associated with deletion, but a subset of them was associated with normal or increased copy number (CN). A consensus 3q13.31 deletion localized to a region within the limbic system-associated membrane protein (LSAMP) gene was also identified. The FISH evaluations demonstrated highly-localized homozygous or heterozygous LSAMP deletions in 6 of 11 primary OS. qRT-PCR evaluations of the two major alternative LSAMP transcripts demonstrated reduced expression of 1b isoform transcript in each of three OS with LSAMP exon 1b deletion. Further, the 1a isoform transcripts in these same OS had either reduced expression or a premature termination codon in LSAMP exon 2. This SNP genotyping study identified chromosomal aberrations associated with disease progression in OS and disclosed LSAMP as a novel tumor suppressor gene in OS. The study also demonstrated that CN and LOH analyses were able to detect distinct subsets of genetic abnormalities in OS.
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Regulation of membrane-type 4 matrix metalloproteinase by SLUG contributes to hypoxia-mediated metastasis.
Neoplasia
PUBLISHED: 08-06-2009
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The hypoxic tumor environment has been shown to be critical to cancer metastasis through the promotion of angiogenesis, induction of epithelial-mesenchymal transition (EMT), and acquisition of invasive potential. However, the impact of hypoxia on the expression profile of the proteolytic enzymes involved in invasiveness is relatively unknown. Membrane-type 4 matrix metalloproteinase (MT4-MMP) is a glycosyl-phosphatidyl inositol-anchored protease that has been shown to be overexpressed in human cancers. However, detailed mechanisms regarding the regulation and function of MT4-MMP expression in tumor cells remain unknown. Here, we demonstrate that hypoxia or overexpression of hypoxia-inducible factor-1alpha (HIF-1alpha) induced MT4-MMP expression in human cancer cells. Activation of SLUG, a transcriptional factor regulating the EMT process of human cancers, by HIF-1alpha was critical for the induction of MT4-MMP under hypoxia. SLUG regulated the transcription of MT4-MMP through direct binding to the E-box located in its proximal promoter. Short-interference RNA-mediated knockdown of MT4-MMP attenuated in vitro invasiveness and in vivo pulmonary colonization of tumor cells without affecting cell migratory ability. MT4-MMP promoted invasiveness and pulmonary colonization through modulation of the expression profile of MMPs and angiogenic factors. Finally, coexpression of HIF-1alpha and MT4-MMP in human head and neck cancer was predictive of a worse clinical outcome. These findings establish a novel signaling pathway for hypoxia-mediated metastasis and elucidate the underlying regulatory mechanism and functional significance of MT4-MMP in cancer metastasis.
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Subcutaneous panniculitis-like T cell lymphoma: familial aggregation while different response to chemotherapy.
Int. J. Hematol.
PUBLISHED: 06-18-2009
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Subcutaneous panniculitis-like T cell lymphoma is a rare disease, characterized by a typical clinical presentation mimicking panniculitis, and is often associated with systemic symptoms including hemophagocytic syndrome. The pathogenesis and etiology of this disease is not fully understood. Here we report two patients coming from the same family. They lived together. The disease afflicted a boy and his elder sister at different time with an interval period of 11 years. Both of them had hemophagocytic syndrome preceding the full-blown manifestations of the lymphoma. However, severity of the disease and the response to chemotherapy is quite different between the two siblings.
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Prognostic significance of a pretreatment hematologic profile in patients with head and neck cancer.
J. Cancer Res. Clin. Oncol.
PUBLISHED: 06-08-2009
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The purpose of this retrospective study was to test whether the pretreatment hematologic profile can predict the prognosis of patients with head and neck cancer.
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Two novel Jk(null) alleles derived from 222C>A in Exon 5 and 896G>A in Exon 9 of the JK gene.
Transfusion
PUBLISHED: 05-30-2009
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Polynesian Jk(null) is well known for its mutation as Intron 5 g>a at the 3 splice acceptor site. After sequencing analysis, however, it was noticed that only three of eight samples with the Jknull phenotype carried typical homozygous Polynesian Jk(null) mutation. Five others were noted to be unreported heterozygous Polynesian Jk(null) mutation. An investigation was then conducted to characterize the underlying mechanism leading to this particular Jk(null) genotype.
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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.