Viropexis and Phagocytosis of Type B (Mouse Mammary Tumor) Virus Particles in vivo

Author(s):  
Gabriel Seman ◽  
Leon Dmochowski

Electron microscope examination of spleen tumors of RIII/Dm female mice with reticulum cell sarcoma revealed the presence of extracellular and budding type C, type B, and intracytoplasmic type A virus particles. Penetration of type B particles into cytoplasm of tumor cells has been observed. It consisted of inclusion of the particles into pinocytotic vesicles and of the release of the nucleoids into the cytoplasmic matrix. They were frequently seen penetrating into tumor cells producing type C or intracytoplasmic type A particles at the same time (Figs. 1 and 2). A similar penetration of other viruses into cells in vitro has been described as viropexis.

1997 ◽  
Vol 273 (3) ◽  
pp. L618-L625 ◽  
Author(s):  
K. Soejima ◽  
S. Fujishima ◽  
H. Nakamura ◽  
Y. Waki ◽  
M. Nakamura ◽  
...  

We examined the expression of interleukin (IL)-8 receptors (Rs), type A (IL-8-RA) and type B (IL-8-RB), on peripheral blood and bronchoalveolar lavage (BAL) fluid neutrophils; we also examined IL-8 and other chemoattractants in the epithelial lining fluid (ELF) of patients with chronic lower respiratory tract infection (CLI) to elucidate the in vivo regulation of IL-8Rs. Neutrophils were stained with monoclonal antibodies specific for IL-8-RA and IL-8-RB. We detected higher levels of IL-8 (81.6 +/- 25.4 ng/ml, mean +/- SE), leukotriene (LT) B4, and IL-1 beta in the ELF of the CLI patients than in their serum (P < 0.05). The expression of IL-8Rs on BAL neutrophils was significantly lower than that on peripheral blood neutrophils (P < 0.01 for both). In vitro analysis showed that low-level IL-8 (50 ng/ml) alone did not affect IL-8R expression but that it was downregulated by high-level IL-8 (500 ng/ml) alone and by low-level IL-8 in combination with LTB4 or IL-1 beta. Staurosporine reduced the downmodulation by low-level IL-8 plus LTB4 or IL-1 beta but not by high-level IL-8 alone. We speculate that pulmonary IL-8-RA and IL-8-RB may have been downmodulated by the combined effect of local chemoattractants through, in part, a protein kinase C-dependent mechanism.


Author(s):  
John L. Swedo ◽  
John H. L. Watson ◽  
R. W. Talley

Most of the models in the studies of breast cancer use murine tissues. Data from these studies, based on the “milk factor” theory, promoted the discovery of the mammary tumor virus (MTV). Electron microscopy of murine tissues, both in vivo and in vitro, and fractions of milk from tumor bearing mice confirmed and described the MTV entity at the ultrastructural level. Application of information obtained from studies of the murine model to the human problem has been difficult in the past for technological reasons, or more importantly, a lack of consistent or controlled sources of human materials. With technological improvements, studies of human material of a more controlled nature, based on population statistics, have been accomplished. The source of tissues studied in this presentation are recurring metastatic nodules from patients who had been treated for breast cancer. Easily accessible nodules from both estrogen treated and untreated patients were compared in this study. No differences were found. Recent reports of virus particles or virus-like particles, particularly of the B type variety, have promoted the search for them in human tissues.


Author(s):  
K. Maruyama ◽  
G. R. Swearingen ◽  
L. Dmochowski ◽  
J. H. Jardine ◽  
G. N. Joiner

Herpestype and type C virus particles are known to produce tumors in animals of certain species, and to be present in a variety of human tissues. Similar particles were found in a horse lymphoma.Electron microscope study was carried out on a tumorous prescapular lymph node from an adult female horse with spontaneous lymphoma. Lymph node cells grown in vitro for a total of 105 days (6th passage) were also studied. The lymph node was infiltrated by blastic cells of reticulum cell type and of lymphoblast type. No virus particles were found in the original lymph node. The cultured cells have a large cytoplasm with well developed rough endoplasmic reticulum and Golgi's apparatus, and an indented nucleus with marginated chromatin. Occasionally, intranuclear fibrous structures were observed. Elongated nuclear protrusion were frequently seen.


1985 ◽  
Vol 58 (6) ◽  
pp. 1942-1948 ◽  
Author(s):  
J. G. Prior ◽  
M. Powlson ◽  
G. M. Cochrane ◽  
C. B. Wolff

Ventilatory kinetics during exercise (30 W for 6 min) were studied in 3 asthmatics, 14 patients with chronic airway obstruction (11 with bronchial or type B disease, 3 with emphysematous or type A disease), and in 5 normal age-matched controls. The measure of ventilatory increase during early exercise, alpha 1–3%, was calculated as (avg minute ventilation over 1st-3rd min of exercise--resting minute ventilation)/(avg minute ventilation over 4th-6th min of exercise--resting minute ventilation) X 100. Arterial pH, PO2, and PCO2 (PaCO2) were measured in vitro at rest and within 20 s of termination of exercise. Respiratory PaCO2 oscillations had previously been monitored at rest in the patients (indirectly as in vivo arterial pH, using a fast-response pH electrode) and quantified by upslope (delta PaCO2/delta t). alpha 1–3% was normal in asthmatics (whose respiratory oscillations as a group showed least attenuation) and in type A patients (whose respiratory oscillations as a group were most attenuated). In type B patients reduction in alpha 1–3% correlated with attenuation of delta PaCO2/delta t (r = 0.75; P less than 0.01). There was no significant correlation between delta PaCO2/delta t and change of in vitro PaCO2 from rest to the immediate postexercise period. These findings are consistent with the hypothesis that attenuation of delta PaCO2/delta t slows ventilatory kinetics during exercise in type B but not type A patients. Intact respiratory oscillations are not necessary for CO2 homeostasis after the first few minutes of exercise.


Author(s):  
S. Fujinaga ◽  
K. Maruyama ◽  
C.W. Williams ◽  
K. Sekhri ◽  
L. Dmochowski

Yumoto and Dmochowski (Cancer Res.27, 2098 (1967)) reported the presence of mature and immature type C leukemia virus particles in leukemic organs and tissues such as lymph nodes, spleen, thymus, liver, and kidneys of SJL/J strain mice with Hodgki's-like disease or reticulum cell neoplasm (type B). In an attempt to ascertain the possibility that this neoplasia may be of viral origin, experiments with induction and transmission of this neoplasm were carried out using cell-free extracts of leukemic organs from an SJL/J strain mouse with spontaneous disease.It has been possible to induce the disease in low-leukemia BALB/c and C3HZB strain mice and serially transfer the neoplasia by cell-free extracts of leukemic organs of these mice. Histological examination revealed the neoplasia to be of either reticulum cell-type A or type B. Serial transfer is now in its fifth passage. In addition leukemic spleen from another SJL/J strain mouse with spontaneous reticulum cell neoplasm (type A) was set up in tissue culture and is now in its 141st serial passage in vitro. Preliminary results indicate that cell-free material of 39th tissue culture passage can reproduce neoplasia in BALB/c mice.


Author(s):  
Y. Ohtsuki ◽  
G. Seman ◽  
J. M. Bowen ◽  
M. Scanlon ◽  
L. Dmochowski

Recently, periodate-lysine-paraformaldehyde (PLP) fixation was reported for immunoelectron microscopy (1). In PLP fixation, carbohydrates are oxidized by periodate and cross-linked by lysine; paraformaldehyde stabilizes proteins and lipids. By using PLP fixation, intracytoplasmic type A viral antigens have been previously demonstrated by immunoperoxidase labeling (2). In the present study, PLP fixation has been applied for the detection of the same antigens in mouse mammary tumor culture cells by both immunoferritin and immunoperoxidase methods. Rabbit anti-intracytoplasmic type A virus serum (anti-A), kindly provided by Dr. M. Muller (3), rabbit anti-strain A mouse mammary tumor virus (anti-MMTV) and preimmune rabbit serum as control were used to detect viral antigens in cells of C3H/HeJ strain mouse mammary tumor culture. Attempts have been also made to demonstrate peroxidase labeling of type C virus particles in frozen sections of an SD-MSV-induced NZB rat bone tumor tissue by rabbit anti-MuLV serum.


2019 ◽  
Vol 2 (4) ◽  
pp. 83-98 ◽  
Author(s):  
André De Lima Mota ◽  
Bruna Vitorasso Jardim-Perassi ◽  
Tialfi Bergamin De Castro ◽  
Jucimara Colombo ◽  
Nathália Martins Sonehara ◽  
...  

Breast cancer is the most common cancer among women and has a high mortality rate. Adverse conditions in the tumor microenvironment, such as hypoxia and acidosis, may exert selective pressure on the tumor, selecting subpopulations of tumor cells with advantages for survival in this environment. In this context, therapeutic agents that can modify these conditions, and consequently the intratumoral heterogeneity need to be explored. Melatonin, in addition to its physiological effects, exhibits important anti-tumor actions which may associate with modification of hypoxia and Warburg effect. In this study, we have evaluated the action of melatonin on tumor growth and tumor metabolism by different markers of hypoxia and glucose metabolism (HIF-1α, glucose transporters GLUT1 and GLUT3 and carbonic anhydrases CA-IX and CA-XII) in triple negative breast cancer model. In an in vitro study, gene and protein expressions of these markers were evaluated by quantitative real-time PCR and immunocytochemistry, respectively. The effects of melatonin were also tested in a MDA-MB-231 xenograft animal model. Results showed that melatonin treatment reduced the viability of MDA-MB-231 cells and tumor growth in Balb/c nude mice (p <0.05). The treatment significantly decreased HIF-1α gene and protein expression concomitantly with the expression of GLUT1, GLUT3, CA-IX and CA-XII (p <0.05). These results strongly suggest that melatonin down-regulates HIF-1α expression and regulates glucose metabolism in breast tumor cells, therefore, controlling hypoxia and tumor progression. 


2019 ◽  
Vol 65 (5) ◽  
pp. 760-765
Author(s):  
Margarita Tyndyk ◽  
Irina Popovich ◽  
A. Malek ◽  
R. Samsonov ◽  
N. Germanov ◽  
...  

The paper presents the results of the research on the antitumor activity of a new drug - atomic clusters of silver (ACS), the colloidal solution of nanostructured silver bisilicate Ag6Si2O7 with particles size of 1-2 nm in deionized water. In vitro studies to evaluate the effect of various ACS concentrations in human tumor cells cultures (breast cancer, colon carcinoma and prostate cancer) were conducted. The highest antitumor activity of ACS was observed in dilutions from 2.7 mg/l to 5.1 mg/l, resulting in the death of tumor cells in all studied cell cultures. In vivo experiments on transplanted Ehrlich carcinoma model in mice consuming 0.75 mg/kg ACS with drinking water revealed significant inhibition of tumor growth since the 14th day of experiment (maximally by 52% on the 28th day, p < 0.05) in comparison with control. Subcutaneous injections of 2.5 mg/kg ACS inhibited Ehrlich's tumor growth on the 7th and 10th days of the experiment (p < 0.05) as compared to control.


Toxins ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 157 ◽  
Author(s):  
Adriana Tomoko Nishiya ◽  
Marcia Kazumi Nagamine ◽  
Ivone Izabel Mackowiak da Fonseca ◽  
Andrea Caringi Miraldo ◽  
Nayra Villar Scattone ◽  
...  

Canine oral mucosal melanomas (OMM) are the most common oral malignancy in dogs and few treatments are available. Thus, new treatment modalities are needed for this disease. Bacillus anthracis (anthrax) toxin has been reengineered to target tumor cells that express urokinase plasminogen activator (uPA) and metalloproteinases (MMP-2), and has shown antineoplastic effects both, in vitro and in vivo. This study aimed to evaluate the effects of a reengineered anthrax toxin on canine OMM. Five dogs bearing OMM without lung metastasis were included in the clinical study. Tumor tissue was analyzed by immunohistochemistry for expression of uPA, uPA receptor, MMP-2, MT1-MMP and TIMP-2. Animals received either three or six intratumoral injections of the reengineered anthrax toxin prior to surgical tumor excision. OMM samples from the five dogs were positive for all antibodies. After intratumoral treatment, all dogs showed stable disease according to the canine Response Evaluation Criteria in Solid Tumors (cRECIST), and tumors had decreased bleeding. Histopathology has shown necrosis of tumor cells and blood vessel walls after treatment. No significant systemic side effects were noted. In conclusion, the reengineered anthrax toxin exerted inhibitory effects when administered intratumorally, and systemic administration of this toxin is a promising therapy for canine OMM.


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