Different Kinds Of Tumors Research Articles

Medicinal Properties of Substances Occurring in Higher Basidiomycetes Mushrooms: Current Perspectives (Review)

This review highlights some of the recently isolated and identified substances of higher Basidiomycetes mushroom origin that express promising antitumor, immune modulating, cardiovascular and antihyper-cholesterolemia, antiviral, antibacterial, antiparasitic, hepatoprotective, and antidiabetic effects. Medicinal mushrooms have a long history of use in folk medicine. Mushrooms useful against cancers of the stomach, esophagus, lungs, etc., are known in China, Russia, Japan, and Korea, as well as the United States and Canada. There are approximately two hundred species of mushrooms that have been found to markedly inhibit the growth of different kinds of tumors. However, most of the mushroom origin antitumor substances have not been clearly defined. Several antitumor polysaccharides, such as hetero-β-glucans and their protein complexes (e.g., xyloglucans, and acidic β-glucan containing uronic acid), as well as dietary fibers, lectins, and terpenoids, have been isolated from medicinal mushrooms. In Japan, Russia, China, and the United States, several different polysaccharide antitumor agents have been developed from the fruiting body, mycelia, and culture medium of various medicinal mushrooms (Lentinus edodes, Ganoderma lucidum, Schizophyllum commune, Trametes versicolor, Inonotus obliquus, and Flammulina velutipes). Both cellular components and secondary metabolites of a large number of mushrooms have been shown to effect the immune system of the host and therefore could be used to treat a variety of disease states. The information presented in this review is helpful in exploring and understanding the rich traditions of medicinal mushrooms in Eastern and Western cultures and medicine.

Therapeutic Effects of Substances Occurring in Higher Basidiomycetes Mushrooms: A Modern Perspective

This review highlights some of the recently isolated and identified substances of higher Basidiomycetes mushrooms origin that express promising antitumor, immune modulating, cardiovascular and hypercholesterolemia, antiviral, antibacterial, and antiparasitic effects. Medicinal mushrooms have a long history of use in folk medicine. In particular, mushrooms useful against cancers of the stomach, esophagus, lungs, etc. are known in China, Russia, Japan, Korea, as well as the U.S.A. and Canada. There are about 200 species of mushrooms that have been found to markedly inhibit the growth of different kinds of tumors. Searching for new antitumor and other medicinal substances from mushrooms and to study the medicinal value of these mushrooms have become a matter of great significance. However, most of the mushroom origin antitumor substances have not been clearly defined. Several antitumor polysaccharides such as hetero-beta-glucans and their protein complexes (e.g., xyloglucans and acidic beta-glucan-containing uronic acid), as well as dietary fibers, lectins, and terpenoids have been isolated from medicinal mushrooms. In Japan, Russia, China, and the U.S.A. several different polysaccharide antitumor agents have been developed from the fruiting body, mycelia, and culture medium of various medicinal mushrooms (Lentinus edodes, Ganoderma lucidum, Schizophyllum commune, Trametes versicolor, Inonotus obliquus, and Flammulina velutipes). Both cellular components and secondary metabolites of a large number of mushrooms have been shown to effect the immune system of the host and therefore could be used to treat a variety of disease states.

Expression of bone morphogenetic proteins in human osteogenic and epithelial tumor cells.

In addition to osteosarcomas some epithelial tumors also show bone induction, which is supposedly due to bone morphogenetic proteins (BMPs). However, the types of BMPs expressed in different kinds of tumors have not been studied extensively. In this study five human osteosarcoma and six human carcinoma cell lines were examined to investigate the bone induction and BMP mRNA expression. The cultured cells were transplanted in the subcutaneous tissue of athymic nude mice with or without diffusion chambers. Reverse transcription-polymerase chain reaction (RT-PCR) was used for the detection of BMP mRNAs. All osteosarcoma cell lines expressing all BMPs (BMP-1 to 7) examined, successfully formed bone or osteoid tissue irrespective of the use of a diffusion chamber. Bone formation was induced by diffusion chamber in an osteosarcoma cell line OST and a gastric adenocarcinoma cell line MKN45. OST cells lacked BMP-3 and 7, and MKN45 cells lacked BMP-3, 5 and 6. Our data suggest that BMP-3, 5, 6 and 7 are not always essential for bone induction in tumor cells.

Lack of effect of eicosapentaenoic acid in preventing cancer cachexia and inhibiting tumor growth

It has been recently reported that a diet enriched in n-3 polyunsaturated fatty acids reduces the growth of different kinds of tumors as well as the host tissue hypercatabolic state frequently associated. The rat ascites hepatoma Yoshida AH-130 is a fast growing tumor that causes a rapid and progressive body weight loss in the host and tissue waste associated with a hypercatabolic condition. Plasma levels of classical hormones and humoral mediators (prostaglandin E2 and tumor necrosis factor-α) are early perturbed after tumor transplantation (Tessitore L., Costelli P. and Baccino F.M. (1993) Humoral mediation for cachexia in tumour-bearing rats. Br. J. Cancer, 67, 16–23). Enhanced protein degradation rates and alteration of lipoprotein lipase activity mainly account for the wasting of protein and adipose mass, respectively. However, the daily intragastric administration of eicosapentaenoic acid (1.5 g/kg body wt) to AH-130 bearing rats was completely ineffective either in preventing tissue waste or in reducing tumor growth. The low degree of differentiation and the high growth rate of the AH-130 hepatoma probably account for this lack of effect.

Characterization of nicotinamide methyltransferase in livers of mice bearing Ehrlich ascites tumors: preferential increase of activity.

There was a 2- to 7-fold increase in nicotinamide methyltransferase activity in the livers of mice and rats bearing seven different kinds of tumors compared with the respective control normal livers, while activity in the tumors themselves was hardly detectable. The activity in the liver started to increase markedly 3-7 days after i.p. transplantation of Ehrlich ascites tumors into the mice, maintaining a plateau up to death. Metabolic conversion of 14C-nicotinamide to 14C-N1-methylnicotinamide was 3-fold higher in the slices of the ascites tumor host liver than in the normal liver, but the conversion to other radioactive metabolites was not significantly different. Nicotinamide methyltransferase was finally purified 20,000-fold with a yield of 4% from the cytosolic fraction of the ascites tumor host liver by means of five purification steps. At every purification step, only one enzyme fraction was detected. The enzyme finally isolated exhibited a single protein band in sodium dodecyl sulfate-polyacrylamide gel electrophoresis, with a molecular weight of 26,000. As for the compounds investigated, including the substrates for methyltransferases other than nicotinamide methyltransferase, only quinoline could be the substrate for enzyme activity. It is suggested that the increase in enzyme activity in the tumor host liver probably derived from the endogenous enzyme preexisting in the liver before tumor transplantation.

Correlation of Tumor Sensitivity to Low-Dose-Rate Irradiation with G 2 /M-Phase Block and Other Radiobiological Parameters

The efficacy of exponentially decreasing low-dose-rate irradiation was compared with that of equivalent doses of multiply fractionated high-dose-rate external-beam irradiation in mice with three different kinds of tumors that varied in terms of alpha/beta ratio, tumor volume doubling times, and cell cycle times. Cell cycle distribution was measured after low-dose-rate and high-dose-rate irradiation. The relative efficacy of low-dose-rate irradiation versus equivalent doses of high-dose-rate irradiation was correlated with the extent of arrest of cells in G2 phase of the cell cycle. Unlike 38C13 murine B-cell lymphoma, neither the HT29 human colorectal xenograft or the SNB75 human glioblastoma xenograft was significantly more sensitive to low-dose-rate than fractionated high-dose-rate irradiation. The 38C13 B-cell lymphoma also had the shortest tumor volume doubling and cell cycle times, the most G2 arrest after low-dose-rate irradiation, more G2 arrest with low-dose-rate than high-dose-rate irradiation, and the highest alpha/beta ratio. The data presented here support the hypothesis that dose-rate effects may be minimal for tumors with small shoulders and large alpha/beta ratios and that arrest of cells in G2 phase plays an important role in cell death mediated by low-dose-rate irradiation. The proliferative rates of tumor cells may modify dose-rate effects further, and the interaction of all of these factors may explain in part the increased efficacy of low-dose-rate irradiation and radioimmunotherapy compared with high-dose-rate irradiation that has been reported in some animal models.

へん平上皮細胞への移行を伴った巨大な歯原性明細胞癌とその病理組織学的研究

Malignant tumor consisting of elk, r. cells is often seen in the kidney and several other organs. This tumor, however, rarely occurs in oral and, maxillofacial regions. We recently experienced a huge clear cell carcinoma in a 79-year-old female, which putatively originated in the mandible, and o expansile into the right maxilla. zygoma, temporal bone, orbital, and partially into the cranium. Lymphnode (LN) metastasis was observed in the right submandibular LN.Histopathologically, the tumor was primarily composed of large sheets and islands of uniform vacuolated and clear cells separated by a mature fibrous connetive tissue. The tumor contained no glandular epithelial cells or myoepithelial cells. PAS positive and diastase digestable granules were observed in a small number of tumor cells.Immunohistochemical examination revealed that the tumor cells focally showed positive reaction to keratin (KT) and epithelial membrane antigen (EMA), but completely negative for actin, S-100, vimentin, and myosin.Ultrastructurally, the tumor cells were characterized by the presence of abundant cytoplasm and lack of intracellular organelles. Tonofilaments and desmosomes were, however, occasionally observed. From all of these findings, it is considered that the tumor cell may be derived from the odontogenic epithelium and mimick to clear cell odontogenic tumor.More interestingly, it was found that the tumor partially showed squamous cell differentiation after chemotherapy and immunotherapy. It is likely that the clear cell tumor may transform into squamous cell during differentiation process or vice versa, or the tumor may initially consist of two different kinds of tumor cells.The histogenesis of the tumor and its potential possiblility to differentiate into squamous epithelium are discussed.

MR Imaging of Spinal Intramedullary Tumors

The MR examinations in 25 patients with intramedullary tumors were analyzed. Seven patients were diagnosed with astrocytoma, 6 ependymoma, 2 unspecified glioma, 3 medulloblastoma, 2 metastasis, one neurinoma, and one teratoma. In 3 patients the diagnosis was uncertain. The tumors frequently involved a large portion of the cord and were often accompanied by intratumor necrosis, cystic degeneration, and edema, which was well demonstrated on MR. Gd-DTPA was used in 6 patients and was helpful in separating solid tumor components from cysts and edema. It was difficult to separate different kind of tumors based on morphologic and signal characteristics on MR. Some prominent features could, however, be distinguished. Complete cystic degeneration was more common in astrocytomas than in other tumors, and ependymomas frequently had a heterogeneous signal pattern on both T1- and T2-weighted sequences. The single teratoma had a characteristic content of fat and calcification, and the melanoma had a signal pattern consistent with blood. CSF pathway spread in cases of medulloblastoma was demonstrated by ill-defined contour of the cord and CSF or tumor nodules on the surface of cord and nerve roots.

Ultrastructure of capillary walls in human brain tumors

Changes in capillary walls between human glial, non-glial and metastatic brain tumors were studied with conventional ultrathin section and freeze-fracture replica techniques. The following results were obtained. (1) In glial tumors, ultrathin section studies showed cell junctions of the capillaries were either short or elongate. Moreover, endothelial hyperplasia, surface infolding of endothelial cells, irregularity of the basal lamina and a large extravascular space were observed. Freeze-fracture replicas of capillary endothelium showed tight junctions as two to seven strands. In addition, pinocytotic vesicles had increased markedly and were an average of 25 per microns 2. Both ultrathin and freeze fracture studies showed that, in contrast to malignant gliomas, there were only slight changes in benign astrocytomas. (2) In non-glial tumors, ultrathin sections showed surface infoldings, increased vesicles, many fenestrations of endothelial cells, irregularity of basal lamina and enlarged perivascular space. Freeze-fracture replicas of vascular endothelium, showed that the average number of pinocytotic vesicles and fenestrations were 25 and 22 per microns 2, respectively. Moreover, the tight junction was composed of one or two strands which appeared to be a discontinuous array of particles. (3) In metastatic brain tumors, ultrathin studies showed capillary endothelia were proliferated, had marked infolding, and showed an increased number of pinocytotic vesicles and many fenestrations. Moreover, short and elongate intercellular junctions were presented but no open junction was detected. Finally the basal lamina lost its three-layered appearance and was irregular in width. Freeze-fracture replicas showed pinocytotic vesicles had increased and were 24 per microns 2 on average in four cases, but fenestrations and tight junctions could not be detected. The most fundamental feature of vessels in these three different kinds of tumors was whether they were fenestrated or not. Glial tumors were non-fenestrated, whereas non-glial and metastatic tumors were fenestrated.

Comparison of Proteinase Activities in Squamous Cell Carcinoma, Basal Cell Epithelioma, and Seborrheic Keratosis

The correlation between proteinase activities and invasive and metastatic potentials was investigated by comparing three different kinds of tumors. Extracts from tumor homogenate of 11 squamous cell carcinoma (SCC), 5 basal cell epithelioma (BCE), and 8 seborrheic keratosis (SK) were prepared in order to examine the activity of acid phosphatase and proteinases such as cathepsin B and D, type I and IV collagenase, and plasminogen activator (PA). There was no difference observed between acid phosphatase and cathepsin D activities among the three tumors. Cathepsin B and PA activities were slightly elevated in SCC. Type I collagenase activity of SCC was 9-fold higher than that of SK (p less than 0.01), and type IV collagenase was 3-fold higher per tissue DNA (p less than 0.05). Type I and IV collagenase of BCE were elevated per tissue protein but not elevated per tissue DNA. Correlation was found between the level of cell differentiation in SCC and the activities of cathepsin B, PA, and type I collagenase. Poorly differentiated SCC exhibited a tendency to have higher proteinase activities. Proteinases that showed high activities in malignant tumor homogenate may be related to the degradation of the surrounding cell matrix in addition to intracellular metabolism. Type I and IV collagenase, in cooperation with cathepsin B and PA, might play a major role in invading the dermal stroma and basement membrane.

Testicular tumors: prospective analysis of real-time US patterns and abdominal staging.

Echomorphologic features of 57 testicular lesions (48 neoplasms, nine benign lesions) were analyzed prospectively by means of high-resolution real-time ultrasonography (US). There was a broad spectrum of texture patterns for testicular malignancies, 92% of which exhibited a predominantly decreased echogenicity compared with that of normal tissue. US findings alone could not be used to make a specific prediction of malignant disease or to classify a neoplasm histologically. However, different kinds of tumors exhibited characteristic echomorphologic features that corresponded to their gross morphologic appearance; a knowledge of these echomorphologic features is extremely useful for the US differentiation of tumors from nonneoplastic scrotal pathologic conditions. All neoplasms in this series displayed distinct abnormalities in parenchymal texture, and all were detected with US. The sensitivity and predictive value of a normal sonogram were as high as 100%. With regard to the detection of retroperitoneal lymph node metastases from testicular tumors, abdominal US had an overall accuracy rate of 96% and was of superior diagnostic value compared with bipedal lymphangiography.

Structural differences in the cell binding region of human fibronectin molecules isolated from cultured normal and tumor-derived human cells

Fibronectins isolated from human plasma (pFN) and from the conditioned media of normal (N-cFN) and tumor (T-cFN) human cells were compared by cathepsin D digestion followed by immunostaining of released fragments with the monoclonal antibody 3E3, specific for the cell binding site. Two different staining patterns were obtained, one specific for pFN and N-cFN, the second common to fibronectins from the 3 different kinds of tumors studied. This indicates structural differences between N-cFN and T-cFN in the cell binding region of the fibronectin molecule.

Applications of dynamic-CT, or angio-CT in neuroradiology. A disappointing experience

The authors expose their experience in neuroradiological applications of dynamic-CT (D-CT) or angio-CT. The examinations are performed by means of a G.E. 8.800 CT/T. A special software offers automatic analysis of the region of interest. Vascular and tumoral patients are examined trying to evaluate: (a) the blood flow in patients suffering from transient ischaemic attacks and (b) to estimate the possibilities of D-CT in the evaluation of tumoral vascularity and in the identification of characteristic curves for different kinds of tumors.

Amylase as an Additional Marker of Salivary Gland Neoplasms: An Immunoperoxidase Study

The presence of amylase in normal and neoplastic salivary gland tissue was investigated by immunoperoxidase techniques. Apart from normal and inflamed parotid glands, different kinds of tumours were studied with regard to amylase: acinic cell tumours, adenocarcinomas, adenoidcystic carcinomas, salivary duct carcinomas, mucoepidermoid tumours and squamous cell carcinomas. Amylase could be seen in acinic cell tumours, but not in other neoplasms. The results were discussed with respect to the diagnostic implications.

Experimental carcinogenesis.Induction of multiple tumors by viruses

Many viruses are able to cause the development of tumors when inoculated into suitable vertebrate hosts. Among them, polyoma virus can induce tumors in several mammalian species: not only many different kinds of tumor, but a large number of tumors within a single individual. Tissue culture studies employing cells from mice and hamsters, as well as observations of the manner of tumor development following polyoma virus injection in these species in vivo, suggest that some, or all, of the tumors so induced are multiple primaries. Because of the availability of mice of different genetic constitutions, the relative ease with which mouse cells from both normal and malignant tissue can cultivate in vitro, the known responses of mice to many carcinogenic agents, as well as the availability of transplantable, metastasizing mouse tumors, it is believed the polyoma virus/mouse host system would provide a highly suitable model in which an experimental approach to the elucidation of mechanisms for the origin of multiple tumors would be possible.

A clinical and pathological staging system for soft tissue sarcomas.

A system for staging the clinical status of patients with soft tissue sarcomas is presented, based on the clinical characteristics of the primary tumor (size, extension), the involvement of lymph nodes, the presence of metastases, and the grade of the tumor. This represents the TNM system with grade of tumor (G) added. The system evolved was based on examination of 1215 cases of 13 types of soft tissues sarcomas, primarily in the extremities (fibrosarcoma, liposarcoma, etc.). Nine stages are described, and they are correlated with survival in the cases reviewed. The staging system now can be used for case evaluation for therapy determination and for intercomparison of series of patients as to incidence of different kinds of tumors, effects of treatment, and survival.

Enzyme histochemical patterns in human tumours—I. Hydrolytic enzymes in carcinoma of the colon and the breast

Enzyme histochemical methods were used to determine the activity of a number of hydrolytic enzymes in mammary and colonic-rectal carcinoma and to compare the activity with that in adjacent normal epithelium. The activity of the hydrolytic enzymes, a possible measure for the degree of differentiation of the cell, shows a general tendency to decrease, exceptions however, being numerous. For instance, a high proportion of the mammary carcinomas have an elevated acid phosphatase activity; some of the colonic-rectal carcinomas have an elevated 5′nucleotidase activity. Variations of the enzyme pattern between different kinds of tumours and between tumours of the same group are large.

Pathology of ulcerogenic and diarrheogenic tumors of the pancreas.

Ulcerogenic and diarrheogenic tumors of the pancreas were studied both light and electron microscopically in the documented cases of two different kinds of tumors to elucidate the histogenesis of non‐beta islet cell tumors in reference to islet cells of the normal pancreas.Argyrophil stain for delta (D) islet cells revealed a few limited number of argyrophil tumor cells, suggesting some relationship to D islet cell as being origin of the ulcerogenic tumor. Alpha (A) cells were not detected in either of ulcerogenic or diarrheogenic tumors. Electron microscopic finding is more confusing. Z‐E tumor granules are heterogenous and variable in relatively smaller sizes of 100–130 mμd 170–200 mμ Diarrheogenic tumors have more homogenously smaller granules (100–130 mμ) with minor components of intermediate sizes (150–200 mμ).Thus, both ulcerogenic and diarrheogenic tumors are quite different from D islet cells (average granule‐350 mμ) or antral G cells (average granule‐250 mμ), both of which are two different gastrin‐producing cells.A tentative conclusion will be that ulcerogenic tumors originate from gastrin cell similar to antral G cell and diarrheogenic tumors stem from gastrin‐antagonist producing cell, presumably similar to the gastric inhibitory peptide (G.I.P.) cell of the small intestine.

Electron microscopy studies on cytologic material acquired by fine needle biopsy.

Tumour material, collected by fine-needle aspiration according to Franzén (4) has been fixed and embedded for study with the transmission electron microscope (TEM). Different kinds of tumours, mainly from the head and neck region as well as experimental animal material (liver and salivary gland tissue from guinea-pigs) have been studied. It is possible to get material of good quality by careful processing of the specimens and the paper contains a number of micrographs showing such specimens. There is every reason to regard the results presented as an indication that electron microscopy can be used for more detailed studies in connection with fine-needle biopsy. It should be tried especially in those cases where it is of interest to follow a tumour during radiotherapy or treatment with antibiotics or cytotoxic drugs.

Whole body autoradiography and fluorography of two tetracycline compounds in tumour-bearing mice.

Abstract 1. The radioactivity and fluorescence distribution pictures of tritium‐labelled tetracycline in some tumour‐bearing mice were investigated by means of autoradiography and fluorescence technique applied to whole body sections. In some tissues, including blood, bone marrow, lung, heart muscle, red pulp and marginal zone of the spleen, thyroid, brown fat, stomach (contents), and kidney, fluorescence was weaker than would be expected from the concentration of the drug. The reasons for this are discussed. A high tissue content of calcium seems to enhance the fluorescence more than can be accounted for only by the concentration. In the von Kossa‐positive parts of an osteosarcoma fluorescence, and to a less extent radioactivity, was strong and persistent. In the two von Kossa‐negative soft tumours fluorescence as well as radioactivity was rather weak.2. After the administration of demethylchlortetracycline to mice bearing ten different kinds of tumours, persisting fluorescence after 24 h was seen only in three osteosarcomas and one mammary carcinoma and was confined to von Kossa‐positive areas.Our results favour the view that tetracyclines are retained in tumour tissue with an increased calcium content, which is probably less important in increasing the real concentration of the drugs than in enhancing their fluorescence.