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At least 433 records · Page 24Linked to original sources

Intracytoplasmic localization of cathepsin D reflects the invasive potential of gastric carcinoma.

BACKGROUND: The present study was undertaken to investigate the role of cathepsin D in the invasiveness of human gastric cancer. METHODS: Immunohistochemical cathepsin D staining was performed in samples from 29 early gastric adenocarcinomas (papillary or tubular adenocarcinoma) and 15 gastric adenomas, and their adjacent nonneoplastic gastric mucosa. We classified the patterns of cathepsin D immunostaining into four types; type A, fine granular staining in the apical portion: type B, intense coarse granular staining in the apical portion; type C, fine granular staining in the basal portion; and type D, diffuse granular staining throughout the cytoplasm. RESULTS: All of the nonneoplastic mucosa showed an apical cytoplasmic distribution pattern (type A or type B). However, 20% (2/10) of low-grade gastric adenomas and 60% (3/5) of high-grade gastric adenomas showed an abnormal staining pattern. i.e., types C and D. Moreover, 82% (9/11) definite intramucosal gastric adenocarcinomas, and the majority of gastric adenocarcinomas with submucosal invasion [83% (15/18) of those in the mucosal part and 100% (14/ 14) of those in the invasive submucosal part] showed an abnormal staining pattern (types C and D). Interestingly, most of the carcinoma cells invading the stroma and lymphatics showed the type D staining pattern. CONCLUSIONS: These results indicate that an abnormal cytoplasmic staining pattern of cathepsin D may reflect the invasive potential of gastric carcinoma cells.

Adenocarcinoma↗

Lymphoscintigraphy in lymphedema: an aid to microsurgery.

The role of lymphoscintigraphy, performed with 99mTc-labeled antimony sulfur colloid, in the diagnosis of lymphedema and as a test for selection of patients for microvascular operation was evaluated in 32 patients with primary and secondary lymphedema and four patients with other causes of leg edema. Lymphoscintigraphy clearly demonstrated if edema was of lymphatic origin. Five different image patterns were identified; abnormal image patterns could not be predicted from clinical history or physical findings. Quantitative evaluation of removal of the radioactive colloid from the injection site and appearance in lymph node sites and liver was of limited usefulness. Nine patients underwent various surgical procedures before or after lymphoscintigraphy. Lympho-venous anastomoses were possible only in patients who had patent lymph channels visible on lymphoscintigrams. Based on initial experience, lymphoscintigraphy seems to be useful to select patients for microvascular operation.

Adolescent↗

CT diagnosis of chyluria after partial nephrectomy.

OBJECTIVE: The purpose of this study was to describe the CT diagnosis of chyluria after partial nephrectomy. CONCLUSION: Fat in the bladder can be identified on CT after partial nephrectomy. This finding is caused by chyluria secondary to lymphatic injury and should not be mistaken for other abnormalities. Our study population did not need treatment of chyluria.

Adult↗

[Studies on toxicity of hydrocortisone 17-butyrate 21-propionate -4. Chronic toxicity in rats by subcutaneous administration (author's transl)].

Chronic toxicity of hydrocortisone 17-butyrate 21-propionate (HBP), a new synthetic corticosteroid, was studied in rats. HBP was subcutaneously injected to rats as the daily doses of 0.001, 0.01, 0.01, 1.0 and 3.0 mg/kg for 6 months, and the following recovery test was carried out for 4 weeks. Hydrocortisone 17-butyrate (HB) and betamethasone 17-valerate (BV) were used as the reference drugs at the doses of 0.1, 1.0 and 3.0 mg/kg. The suppression of body weight gain by the administration of HBP was observed at the doses more than 1.0 mg/kg in male and more than 0.1 mg/kg in female, and the dead animals were sent at the highest dose of HB and BV. Mainly at the doses more than 0.1 mg/kg HBP induced the dose-dependent symptoms such as decrease in the number of white blood cells and total protein level in serum, and increase in total cholesterol, GOT and GPT level in serum, and atrophic changes of adrenals, lymphatic tissues, skin and subsexual organs. No usual abnormality was recognized at the doses less than 0.01 mg/kg of HBP. These symptoms were more toxic in male, and the strength of toxicity was in the order of BV greater than HB greater than HBP. Many of these findings have known as common effects of corticosteroids. The changes observed in this study were almost recovered after withdrawal of HBP at the doses less than 0.1 mg/kg. As the result, it was suggested that the maximum non-toxic dose of HBP was 0.001 mg/kg.

Administration, Topical↗

Tumor microenvironment abnormalities: causes, consequences, and strategies to normalize.

A solid tumor is an organ-like entity comprised of neoplastic cells and non-transformed host stromal cells embedded in an extracellular matrix. The expression of various genes is influenced by interactions among these cells, surrounding matrix, and their local physical and biochemical microenvironment. The products encoded by these genes, in turn, control the pathophysiological characteristics of the tumor, and give rise to the abnormal organization, structure, and function of tumor blood vessels. These abnormalities contribute to heterogeneous blood flow, vascular permeability, and microenvironment. Proliferating tumor cells produce solid stress which compresses blood and lymphatic vessels. As a result of vessel leakiness and lack of functional lymphatics, interstitial fluid pressure is significantly elevated in solid tumors. Each of these abnormalities forms a physiological barrier to the delivery of therapeutic agents to tumors. Furthermore, the metabolic microenvironment in tumors such as hypoxia and acidosis hinder the efficacy of anti-tumor treatments such as radiation therapy and chemotherapy. A judicious application of anti-angiogenic therapy has the potential to overcome these problems by normalizing the tumor vessels and making them more efficient for delivery of oxygen and drugs. Combined anti-angiogenic and conventional therapies have shown promise in the clinic.

Animals↗

Laser therapy for lymphatic malformations of the upper aerodigestive tract. An evolving experience.

Lymphatic malformations of the upper aerodigestive tract can present therapeutic challenges. Symptoms associated with these lesions include bleeding, dysphagia, changes in speech, and dyspnea. Surgical therapy is recommended, which often leads to functional interference and cosmetic deformities. Laser photocoagulation of these malformations can control symptoms and may be repeated as necessary, preserving tissue and function. The results in four patients treated with the carbon dioxide laser and in five patients treated with the neodymium-YAG laser were reviewed. Reduction of bulk and improvement of symptoms were achieved in all patients, most of whom required multiple treatments. The average duration of each procedure was 30 minutes. All patients were discharged from the hospital on the same day or 1 day after laser therapy with minimal morbidity. The indications, evolving technique, and results of laser therapy are discussed.

Adolescent↗

Reversed intestinal rotation associated with anomalous mesenteric venous drainage. Report of a case.

Reverse intestinal rotation is a congenital abnormality of midgut rotation. Mesenteric arterial, venous, and lymphatic compression may occur, but associated anomalous mesenteric venous drainage is extremely rare. The case presented illustrates the importance of recognition of intestinal malrotation and the danger of bowel resection in the presence of anomalous mesenteric venous drainage.

Adult↗

Mechanisms of tissue damage resulting from the use of oral water irrigation devices.

Oral water irrigation devices (WIDs) are widely used for oral physiotherapy in homes and dental clinics throughout the world. A major area of concern in the use of WIDs has been the possibility of injury to the sulcular epithelium and underlying tissue. There are several documented clinical cases of tissue injury with the use of WIDs. The existing WIDs exert excessive pressures on the sulcular epithelium. Although it is known that the high jet impact pressures exerted by the WIDs cause the tissue damage, the underlying damage mechanisms are poorly understood. The damage to the sulcular epithelium and underlying tissue is mediated through several physiological and micromechanical processes and includes, among others, the following damage mechanisms: pressure-induced, diffusion-mediated, deposition of bacteria and toxins into the underlying tissue, damage to the collagen network integrity in the tissue, damage to the blood and lymphatic microcirculation, especially damage to the anchoring filaments attached to the terminal lymphatic wall, and direct mechanical damage due to abnormal shear forces induced by the jet. All these damage processes could lead to tissue necrosis.

Humans↗

Time response of interstitial fluid pressure measurements in cervix cancer.

Increased interstitial fluid pressure (IFP) is a common finding in malignant tumors as a result of the abnormal tumor vasculature and a lack of functional lymphatics. A recent clinical study by Milosevic et al. [Cancer Res. 61 (2001) 6400] reported a link between elevated IFP and survival in patients with cancer of the cervix. Patients with high IFP were more likely to have recurrence of tumors even after radiotherapy and were also more likely to die of progressive disease, independent of other prognostic factors. In this complementary study, using human data, we analyze 152 cervical tumor pressure IFP measurements from 42 patients with clinically diagnosed cancer of the cervix, randomly selected from the sample of 102 patients involved in the original study. We propose a simple biophysical model, based on flow through porous media, to explain the time response of the measured pressure curves in human cervical tumors. The response of IFP was governed by a time-constant tau(IFP) = 14 +/- 1 s averaged over multiple tumor sites. Interstitial hydraulic conductivity was computed to be approximately equal to 4.3 x 10(-6) cm(2)/mm Hgs.

Biophysical Phenomena↗

Retroaortic left renal vein in testicular cancer patient: potential staging and treatment pitfall.

A 20-year-old man was diagnosed with a left mixed germ cell testicular tumor and clinical staging with computerized tomography suggested left para-aortic subhilar retroperitoneal adenopathy. The patient received 4 cycles of cisplatin, vinblastine and bleomycin chemotherapy but the mass in the left renal hilus area remained unchanged. Subsequent retroperitoneal lymphadenectomy revealed the mass to be a retroaoritc left renal vein type 2. Further confusion occurred during followup in differentiating this anomaly from recurrent neoplasm necessitating evaluation by magnetic resonance imaging. Retroaortic left renal vein represents a potential imaging pitfall in testicular cancer that may facilitate suboptimal staging, treatment and followup.

Adult↗

Dissecting tumour pathophysiology using intravital microscopy.

For a systemically administered therapeutic agent to reach neoplastic cells, it must enter the blood circulation, cross the vessel wall, move through the extracellular matrix and avoid getting cleared by the lymphatics. In tumours, each of these barriers is abnormal, changes with space and time, and depends on host-tumour interactions. Intravital microscopy has provided unprecedented molecular, cellular, anatomical and functional insights into these barriers and has revealed new approaches to improved detection and treatment.

Animals↗

Biodistribution and pharmacokinetics of variously sized molecular radiolabelled polyethyleneiminomethyl phosphonic acid as a selective bone seeker for therapy in the normal primate model.

An ideal radiopharmaceutical for the treatment of neoplastic and inflammatory (benign) bone disease would be a radiolabelled compound that predominantly accumulates in bone lesions with limited access to normal bone and other organs. Neoplastic tissue's abnormal blood supply (increased permeability) and lack of lymphatics will selectively accumulate radiolabelled macromolecules. This enhanced permeability and retention effect forms the basis of this study, using various molecular sizes of the radiolabelled macromolecule polyethyleneiminomethyl phosphonic acid (PEI-MP) for increased selectivity of the bone-seeking radiopharmaceutical. PEI-MP was synthesized by condensation of polyethyleneimine, phosphonic acid and formaldehyde, followed by fractionation into different molecular sizes by membrane ultrafiltration. Labelling efficiency to 99mTc (as radiotracer) was approximately 99% with complexes stable for 24 h. The pharmacokinetics and biodistribution of various 99mTc-PEI-MP fractions were investigated using 4 experimental baboons (Papio ursinus) per fraction. Scintigraphy was performed on the baboons under general anaesthesia of pentobarbital i.v. After an i.v. bolus of 99mTc-PEI-MP (approximately 185 MBq) both dynamic studies (30 x 1 min frames), and static studies (2 min acquisition every hour for 4 h) were done, as well as blood samples and urine collected. From the results macromolecules with sizes ranging between 30-300 kDa were characterized by excessive liver (21%-57% retained activity) and kidney (40% retained activity) uptake and accompanying long residing times (t1/2 up to 24 h). The percentage bone uptake averaged at 8% for these particles excluding sizes 100-300 kDa where very little bone uptake was seen (< 1%). In this case the blood clearance was also slow (t1/2 approximately 2 h). The fraction size 10-30 kDa had comparatively low accumulation and short residence times in the liver and kidneys (resp. 20%, t1/2 = 22 +/- 4 min; 17.5%, t1/2 = 20 +/- 3 min) and although the bone uptake of 18% in this case was high, it is still low for a bone-seeking agent. These particles cleared the blood with t1/2 = 25 +/- 2 min and seemed suitable for labelling with a therapeutic radioisotopic agent.

Animals↗

[Colchicine sensitivity index: a means of distinguishing benign and malignant lymphocytic cutaneous infiltrates (author's transl)].

Lymphocytes in patients with chronic lymphatic leukaemia and other malignant lymphomas have an abnormally high sensitivity to colchicine in vitro. This can be expressed in a colchicine-sensitivity index and used diagnostically. Lymphocytes isolated from cutaneous infiltrates in mycosis fungoides, a cutaneous malignant T-cell lymphoma, had an increased colchicine-sensitivity index of 44 (P < 0.01). On the other hand, lymphocytes from cutaneous infiltrates of reactive inflammatory dermatitis cases had an index of 23. It would seem that the colchicine-sensitivity index is helpful in the diagnosis of selected cases of cutaneous malignant lymphomas.

Adult↗

[Ultrastructural morphology of Kaposi sarcoma of the head and neck in acquired immunodeficiency syndrome (AIDS)].

The ultrastructural morphology of Kaposi's sarcoma in the skin and mucous membranes of the head and neck regions of patients with acquired immune deficiency syndrome (AIDS) was examined electron microscopically. It was found that the tumour consisted of neoplastic spindle cell aggregates, vascular endothelial cell proliferations and an inflammatory infiltrate of lymphocytes and plasma cells. Not only abnormal blood vessel endothelial proliferations, but also irregular lymphatic luminal formations were observed. Moreover, tubuloreticular structures, helical polysomes, giant multivesicular bodies as well as test-tube and ring-shaped forms were found in the tumour cells. Erythrophagocytosis in various stages including ultimately the production of siderosomes was also seen. There was also some mitotic activity in the tumour cells. Retroviruses of 100-120 nm, morphologically identical to HTLV-III, were budding from the plasma membrane of some of the Kaposi's sarcoma cells. As these retroviruses are able to replicate in Kaposi's sarcoma cells without having a clear relation to the tumourogenesis, the characterisation as well as quantification of the virus-producing cells may well prove highly relevant.

Acquired Immunodeficiency Syndrome↗

Computed tomography of mediastinal lymph nodes in nonsmall cell lung cancer. A new approach based on the lymphatic pathway of tumor spread.

Computed tomography was used to evaluate mediastinal lymph nodes in 97 patients with nonsmall cell lung cancer. All patients had thorough surgical-pathological determination of mediastinal node status. Twenty-three patients were found to have metastatic lymph nodes. The usual lymphatic pathways of tumor spread into the mediastinum were defined using the node mapping scheme suggested by the American Thoracic Society. We considered mediastinal nodes abnormal when the short axis of the largest mediastinal node in the lymphatic drainage territory of the cancer was greater than or equal to 10 mm and the difference between this node and the largest node in the other territories is greater than 5 mm. The sensitivity was 78%, the specificity 99%, the positive predictive value 95%, the negative predictive value 94%, and the accuracy 94%. Comparing our method to those that used the size criterion alone, the number of false positives was reduced.

Adult↗