A 74-year-old woman with massive bilateral pleural effusion, which was exudative in nature, and with mononuclear cell predominance underwent a pleuroscopy. Parietal pleura were thickened and partly reddish in color. Biopsy specimens taken from the parietal pleura revealed lymphoplasmacytic inflammation with fibrosis. As her performance status rapidly worsened with thoracentesis, we performed bilateral pleurodesis using talc. Pathologic evaluation of the pleural biopsy specimen with immunohistochemical staining revealed 91 IgG4-positive plasma cells per high-power field and an IgG4/IgG ratio of 91%. Thus, the diagnosis of pleuritis from IgG4-related disease was established. Our case suggests that IgG4-related disease is one of the causes of pleural effusion, and it should be included in the differential diagnosis of unexplained pleuritis.
We report a case of a 64-year-old woman with Stage IV breast cancer who responded well to chemotherapy containing bevacizumab. She noticed a left breast tumor with acute progression and was diagnosed as having Stage IV, estrogen receptor( ER)(-), progesterone receptor(PgR)(-), human epidermal growth factor receptor 2(HER2)(-)breast cancer (T4cN3cM1[lymph nodes]). She received 5 courses of adriamycin(60mg/m / 2)plus cyclophosphamide(600mg/m2)(AC therapy)and 4 courses of weekly paclitaxel(PTX 90mg/m / 2)plus bevacizumab(AVA 10 mg/m2)as systemic therapy. Computed tomography(CT)and magnetic resonance imaging(MRI)revealed a complete response(CR). After local resection of the breast tumor and radiation to the breast and regional lymph nodes, capecitabine therapy was initiated. Currently, at 5 months after surgery, no new lesion has been detected.
Paraquat is a fast acting nonselective contact herbicide that is extensively used worldwide. However, the aqueous solubility and soil sorption of this compound can cause problems of toxicity in nontarget organisms. This work investigates the preparation and characterization of nanoparticles composed of chitosan and sodium tripolyphosphate (TPP) to produce an efficient herbicidal formulation that was less toxic and could be used for safer control of weeds in agriculture. The toxicities of the formulations were evaluated using cell culture viability assays and the Allium cepa chromosome aberration test. The herbicidal activity was investigated in cultivations of maize (Zea mays) and mustard (Brassica sp.), and soil sorption of the nanoencapsulated herbicide was measured. The efficiency association of paraquat with the nanoparticles was 62.6 ± 0.7%. Encapsulation of the herbicide resulted in changes in its diffusion and release as well as its sorption by soil. Cytotoxicity and genotoxicity assays showed that the nanoencapsulated herbicide was less toxic than the pure compound, indicating its potential to control weeds while at the same time reducing environmental impacts. Measurements of herbicidal activity showed that the effectiveness of paraquat was preserved after encapsulation. It was concluded that the encapsulation of paraquat in nanoparticles can provide a useful means of reducing adverse impacts on human health and the environment, and that the formulation therefore has potential for use in agriculture.
We describe rare primary pulmonary mucinous (colloid) adenocarcinoma in an 80-year-old man. Chest computed tomography revealed a lobulated, well-defined nodule with a diameter of 3.2 cm in the right middle lobe. Transbronchial biopsy via endobronchial ultrasound with a guide sheath did not uncover malignancy. Right middle lobectomy proceeded because the tumor was located close to the pulmonary hilum. Macroscopically, the cut surface of the nodule comprised a well demarcated area of somewhat transparent granular aggregates and a yellow-white gelatinous substance. Computed tomography findings of a solitary metastatic lesion in the left fifth costal head 28 months thereafter were consistent with those of a mucin-rich tumor, which was effectively treated by radiotherapy.
Drug-induced liver injury (DILI) is a leading cause of acute liver failure in developed countries. Hepatotoxicity is a well-recognized adverse effect associated with synthetic oestrogens, which can cause cholestasis. The current report describes ethinyloestradiol (EE2)-associated highly unusual adverse effects of autoimmune hepatitis (AIH) and microvesicular steatosis (MS). DILI that fulfils the criteria for AIH is referred to as drug-induced autoimmune hepatitis (DIAIH). MS is a potentially severe liver lesion that results from mitochondrial dysfunction. We explore the pathophysiological mechanisms underlying DIAIH and MS.
A 50-year-old man was referred to our hospital because of a 2-month history of painful gingival swelling. Histopathological examination of the biopsy specimen showed a metastatic adenocarcinoma, and a chest-abdominopelvic CT showed multiple metastases in the lung, liver, and spleen, but failed to demonstrate the primary tumor. He had never complained of abdominal symptoms, and physical examination did not show any abnormality in the abdomen. However, immunohistochemical staining including caudal-related homeobox transcription factor (CDX-2) of the gingival tumor and PET-CT findings strongly suggested colorectal cancer as the origin. Colonoscopy then revealed a tumor in the rectum, and systemic chemotherapy was started immediately.
We performed radiotherapy in a 28-year-old patient with Kimura's disease of the orbit. Irradiation with 21.6 Gy was administered to the tumor bed with a single dose of 1.8 Gy in 5 weekly fractions delivered via a high-energy linear accelerator (6-MV X-ray). Complete remission of the tumor and improvements in the neurological findings were achieved. Neither tumor regrowth nor late complications were detected up to 84 months after radiotherapy. Radiotherapy is an effective treatment for Kimura's disease of the orbit.
We herein report a case of primary lymphoma of the prostate, which arose in an 85-year-old male with dysuria. CT and MRI examinations demonstrated a large mass in the prostate. A transrectal ultrasound-guided biopsy of the prostate was performed. The histological examination showed diffuse large B-cell lymphoma. The large lesion in the prostate showed spontaneous regression. Spontaneous regression of primary lymphoma of the prostate has not been reported previously. The spontaneous regression of primary lymphoma of the prostate observed in this patient suggests that observation may represent a viable treatment option following a biopsy that has provided a histopathological diagnosis.
Metastatic cancer cells degrade extracellular matrix containing collagen. In this study, a variety of different polymer prodrugs have been synthesized and embedded in collagen gels for application in a metastasis-associated drug delivery system (DDS). Dendrimer-doxorubicin (Dox) prodrugs were prepared with different surfaces, including collagen peptides and polyethylene glycol. Furthermore, Dox was conjugated to linear poly(glutamic acid) (poly-Glu) instead of the dendrimer. The cytotoxicities of each of these polymer prodrug systems against the poorly invasive MCF-7 and highly invasive MDA-MB-231 cells were similar. The highly invasive MDA-MB-231 cells, however, were more sensitive than the MCF-7 cells to the polymer prodrugs-embedded collagen gels, suggesting that these polymer prodrugs/collagen hybrid gels would be useful for the development of metastasis-associated DDSs. The cytotoxicities of the polymer prodrugs were dependent on their chemical compositions. The collagen peptide-conjugated dendrimer prodrug/collagen hybrid gel demonstrated in vivo anticancer effects in an orthotopic metastatic mouse model.
Elevated soluble interleukin-2 receptor (sIL-2R) in sera is observed in patients with malignant lymphoma (ML). Therefore, sIL-2R is commonly used as a diagnostic and prognostic marker for ML, but the mechanisms responsible for the increase in sIL-2R levels in patients with B-cell lymphomas have not yet been elucidated. We first hypothesized that lymphoma cells expressing IL-2R and some proteinases such as matrix metalloproteinases (MMPs) in the tumor microenvironment can give rise to increased sIL-2R in sera. However, flow cytometric studies revealed that few lymphoma cells expressed IL-2R ? chain (CD25) in diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL), and most CD25-expressing cells in the tumor were T-cells. Distinct correlations between CD25 expression on B-lymphoma cells and sIL-2R levels were not observed. We then confirmed that MMP-9 plays an important role in producing sIL-2R in functional studies. Immunohistochemical (IHC) analysis also revealed that MMP-9 is mainly derived from tumor-associated macrophages (TAMs). We therefore evaluated the number of CD68 and CD163 positive macrophages in the tumor microenvironment using IHC analysis. A positive correlation between the levels of sIL-2R in sera and the numbers of CD68 positive macrophages in the tumor microenvironment was confirmed in FL and extranodal DLBCL. These results may be useful in understanding the pathophysiology of B-cell lymphomas.
Natural products obtained from marine invertebrates such as sponges and tunicates are attractive sources of drugs. However, a critical obstacle in the development of these compounds is the problem of supply. In most cases, neither chemical synthesis nor mariculture of invertebrates is economically feasible. Due to structural similarities, many marine natural products are suspected to be produced by associated microorganisms. A favorable strategy for the production of such compounds is to use culturable microorganisms. Here we report that didemnin B, a tunicate-derived depsipeptide, has been isolated from a culturable bacterium, Tistrella mobilis YIT 12409.
We present a case of post-traumatic diaphragmatic herniation of the liver, which mimicked an intrathoracic tumor. After an automobile accident, the patient underwent thoracotomies for hemothorax and lung cancer in the right chest. Seven months later, computed tomography (CT) demonstrated a round tumor in the thorax adjacent to the right diaphragm with a higher density than the liver parenchyma. An intrathoracic tumor including a primary or metastatic lung cancer was suspected. However, positron emission tomography (PET) showed that the uptake of fluorine-18-fluorodeoxyglucose (FDG) was identical to that in the liver, and the tumor appeared to be contiguous with the liver. Thus, we suspected liver herniation. Core needle biopsy revealed liver cells without neoplastic tissue. Upon surgical exploration, herniation of the liver was found and repaired. PET was helpful in providing morphological and functional information leading to accurate diagnosis of liver herniation in this unusual case.
Coupled oxidation of [tetraarylporphyrinato]iron(III) chloride carrying substituents in the ortho or para positions was performed by allowing the iron porphyrin to react with dioxygen, ascorbic acid, and pyridine to give biladienone as the major product and bilindione as a minor one. Efforts to find reaction conditions and workup procedures to obtain bilindione improved the yields of triarylbilindiones ranging between 2% and 19%. Electron-withdrawing substituents in the para position on the aryl groups increased the selectivity of bilindione relative to biladienone: the isolated yields of bilindione and biladienone were 2% and 85% (OMe), 6% and 44% (COOMe), and 7% and 28% (CN), respectively. Electronic effects of substituents affected both isolation procedures and the spectroscopic properties of bilindiones. Tri(4-methoxyphenyl)bilindione showed a red-shifted electronic absorption compared to unsubstituted and 4-methoxycarbonyl substituted analogues. This was ascribed to the destabilization of the HOMO-1 level by the methoxy groups.
A 79-year-old woman was found to have an abnormal shadow on chest radiography. Computed tomography demonstrated a pleural mass. The F-18 fluorodeoxyglucose positron emission tomography (FDG PET) was performed to determine whether the pleural mass was benign or malignant. The histologic examination of the resected mass showed a unilocular mesothelial cyst of the pleura. The FDG PET findings of a mesothelial cyst of the pleura have not yet been previously reported. The FDG PET findings of a mesothelial cyst in the pleura reflected the microscopic findings of the resected mass. The FDG PET findings, therefore, seem to be useful in the diagnosis of mesothelial cysts.
The goal of this study was to investigate the relationship among immunohistochemical expression of epithelial growth factor receptor (EGFR) family proteins, p21, p27 and prognosis in patients with high-grade astrocytoma. Expression of EGFR family proteins (c-erbB-1, c-erbB-2, c-erbB-3, c-erbB-4), p21 and p27 and Ki-67 labeling index (LI) were studied in 59 samples of high-grade astrocytoma. Expression of protein levels was analyzed by immunohistochemical staining of formalin-fixed and paraffin-embedded sections. Results were analyzed in relation to age, gender and survival. Overexpression of c-erbB-1, c-erbB-2, c-erbB-3 and c-erbB-4 was found in 40 (67.8%), 17 (28.8%), 3 (5.1%) and 42 (75.0%) samples, respectively. Similarly, low expression of p21 and p27 was observed in 50 (84.8%) and 27 (45.8%) samples. Mean Ki-67 LI was 17.3 +/- 1.1. Cox multiple regression analysis showed that c-erbB-1 (Hazard rate(HR) 1.57, 95% Confidence interval (CI) 1.08-2.36; p = 0.017), c-erbB-4 (HR 1.79, 95% CI 1.20-2.74; p = 0.004) and p27 (HR 0.50, 95% CI 0.30-0.82; p = 0.006) were significantly associated with survival. High expression of c-erbB-1 and c-erbB-4 and low expression of p27 were associated with poor prognosis in these patients.
Zoanthids (Cnidaria, Hexacorallia) of the genus Epizoanthus are often found in association with other marine invertebrates, including gastropods and hermit crabs. However, little information exists on the specificity and nature of these associations due to a lack of investigation into Epizoanthus species diversity, and the taxonomy of Epizoanthus is therefore confused. In this study, analyses of morphological data (tentacle number, polyp size, etc) and molecular data (mitochondrial cytochrome oxidase subunit 1 = COI, 16S ribosomal DNA = 16S rDNA) were used to examine Epizoanthus specimens from Tosa Bay, Kochi, Japan. The Epizoanthus specimens were found on both live gastropods (Gemmula unedo) and hermit crabs (Paguristes palythophilus) inhabiting G. unedo and G. cosmoi shells. While morphological analyses did not show clear differences between examined specimens, both COI and mt 16S rDNA clearly divided the specimens into two groups, one associated only with hermit crabs (= Epizoanthus sp. C), and another associated only with living gastropods (= Epizoanthus sp. S). Unexpectedly, DNA sequences from both groups did not match with two previously reported Epizoanthus species from Japan (E. indicus, E. ramosus), indicating they both may be undescribed species. These results highlight the utility of DNA "barcoding" of unknown zoanthids, and will provide a foundation for re-examinations of Epizoanthus species diversity and specificity, which will be critical in understanding the evolution of these unique marine invertebrates.
To elucidate the mechanism of radiation-induced cancers, molecular analysis of cancers in atomic-bomb survivors is important. In our study, we developed a custom oligonucleotide array of 208 genes. We analyzed gene expression profiles of gastric cancers (GCs) from atomic-bomb survivors and identified 9 genes with significantly lower expression in GCs from exposed patients than in GCs from nonexposed patients. Among these 9 genes, expression of versican and osteonectin was investigated in greater detail using immunohistochemistry in 116 GCs from 64 exposed and 52 nonexposed patients who developed GC after the bombing. In the Stage I/II GCs, the clinicopathologic, phenotypic and proliferative characteristics of GCs from exposed and nonexposed patients did not differ significantly; however, versican and osteonectin were expressed at much lower levels in the area of tumor-associated stroma of exposed patients than in nonexposed patients (p = 0.026 and p = 0.024, respectively). These results suggest that the characteristics of tumor-associated stromal cells differ between GCs from exposed and nonexposed patients.
Metastasis is a characteristic property of cancer cells, which degrade extracellular matrix containing collagen. We prepared a polymer prodrug-embedded collagen gel for metastasis-associated drug delivery. A collagen peptide-modified dendrimer that attached doxorubicin (Dox) via a pH-degradable linkage was synthesized as a polymer prodrug. Compared with free Dox, the diffusion of the dendrimer prodrug from the collagen gel was suppressed. Highly invasive MDA-MB-231 cells were more sensitive to the prodrug-hybrid collagen gel than poorly invasive MCF-7 cells, even though the cytotoxicity of the dendrimer prodrug by itself against these cells was almost identical. The cytotoxicity against MDA-MB-231 cells decreased in the presence of a matrix metalloproteinase (MMP) inhibitor, suggesting that the dendrimer prodrug/collagen hybrid gel was affected by MMP activity. The dendrimer prodrug/collagen hybrid gel not only suppressed tumor growth but also attenuated metastatic activity in vivo. Therefore, the dendrimer prodrug-embedded collagen gel is useful for cancer chemotherapy.
Schwannomas are benign tumors mostly arising from the head and neck. Retroperitoneal schwannomas are rare. Here we report the case of a 68-year-old woman with multiple retroperitoneal schwannomas. An abdominal computed tomography (CT) scan showed 1 non-enhancing mass with a low-density area, 4.6 cm in diameter, in the left adrenal region and another non-enhancing mass with a low-density area, 2.9 cm in diameter, in the para-aortic region. The patient had regularly undergone CT scans for malignant tumor screening in maintenance dialysis patients. Retrospectively, the 2 tumors had existed in the same regions in previous CT scans and had gradually increased in size. The tumors were completely resected. Pathological diagnosis of both tumors was schwannoma. When a CT scan shows a slowly growing retroperitoneal tumor with a low-density area, schwannoma should be considered. If the tumor increases in size, complete resection should be performed for pathological diagnosis.
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