Unusual Synchronous Presentation of Maxillary Sinus Fibrosarcoma and Gemistocytic Astrocytoma with a Complication Called Leukocytoclastic Vasculitis: A Case Report

PubMed Central

Cadir, Bilge; Karahan, Nermin; Nasir, Serdar; Aydin, M. Asim; Turkaslan, S. Suha

2009-01-01

Fibrosarcoma of the paranasal sinuses is extremely rare pathology and there is limited report in the literature. We report synchronous presentation of maxillary sinus fibrosarcoma and gemistocytic astrocytoma which is, to our knowledge, unique in the literature. Both tumors metastases to other organ rarely and the metastatic spread of gemistocytic astrocytoma to fibrosarcoma or vice versa have also not been reported in the literature yet. This report discusses the clinical course of the disease, outcome of the treatment approach and survival as well as an unusual occurrence of leukocytoclastic vasculitis during the course of radiotherapy in such unusual presentation. PMID:19756200

Nasal cavity ossifying fibrosarcoma: an unusual fibro-osseous neoplasm.

PubMed

Alameda, Yadiel A; Perez-Mitchell, Carlos; Busquets, José M

2010-11-01

We describe the case of a 65-year-old woman who presented with left nasal obstruction. Clinical and radiographic examinations revealed the presence of a soft-tissue mass that had obliterated the left nasal cavity. The mass was completely excised via an endoscopic approach. Histopathologic examination identified the tumor as an ossifying fibrosarcoma. The patient recovered uneventfully and remained free of disease at the 2-year postoperative follow-up. To the best of our knowledge, no case of an ossifying fibrosarcoma of the nasal cavity has been previously reported in the English-language literature. We discuss the features of this case and the clinical presentation, diagnosis, and management of fibrosarcomas of the nasal cavity and paranasal sinuses.

Bacopa monniera Linn. extract modulates antioxidant and marker enzyme status in fibrosarcoma bearing rats.

PubMed

Rohini, G; Sabitha, K E; Devi, C S Shyamala

2004-08-01

Antioxidative property and tumor inhibitive property of B. monniera (20mg/kg body wt, sc) was examined in 3-methylcholanthrene induced fibrosarcoma rats. Antioxidant enzymes such as catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) and the levels of glutathione (GSH) and the rate of lipid peroxidation (LPO) in the liver and kidney tissues were assessed. A significant increase was noted for the rate of LPO with a corresponding decrease in the antioxidant enzyme status in fibrosarcoma bearing rats. In fibrosarcoma bearing rats, the tumor markers like lactate dehydrogenase (LDH), creatine kinase (CK), alanine transaminase (ALT), aspartate transaminase (AST) and sialic acid (SA) were increased in the serum. Treatment with B. monniera extract significantly increased the antioxidant enzyme status, inhibited lipid peroxidation and reduced the tumor markers. It can be concluded that B.monniera extract promotes the antioxidant status, reduces the rate of lipid peroxidation and the markers of tumor progression in the fibrosarcoma bearing rats.

Effect of alpha-tocopherol on lipid peroxidation and antioxidant system in fibrosarcoma bearing rats.

PubMed

Vasavi, H; Thangaraju, M; Sachdanandam, P

1994-02-23

The anticarcinogenic activity of alpha-tocopherol (Vitamin E) was tried in fibrosarcoma induced rats through its antioxidative potential. The rate of formation of malondialdehyde (MDA), the end product of lipid peroxidation was analysed in alpha-tocopherol (400 mg/kg body weight) treated and untreated fibrosarcoma bearing rats with respective controls. The levels of non-enzymic antioxidants like, glutathione and vitamin E, and enzymic antioxidants viz., catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), and glutathione-S-transferase (GST) were assayed as well. Significantly increased (p < 0.001) level of lipid peroxide was observed with concomitant decreases in the level of enzymic and non-enzymic antioxidants in fibrosarcoma bearing rats when compared with control animals. In alpha-tocopherol supplemented animals, the corrected level of these parameters were observed likely to near normal values. Thus, alpha-tocopherol can be accepted to pose first line of defense mechanism against excessively formed reactive species due to impaired antioxidant systems in fibrosarcoma conditions, that cause membrane damage leading to deleterious effects.

Primary Central Nervous System Fibrosarcoma.

PubMed

Vinodh, V P; Harun, Rahmat; Sellamuthu, Pulivendhan; Kandasamy, Regunath

2017-08-01

We report a rare case of a young female with primary brain fibrosarcoma, and to the best of our knowledge, we believe that only <50 cases have been reported or described worldwide so far. Fibrosarcoma is a malignant neoplasm, in which histologically the predominant cells are fibroblasts that divide excessively without cellular control and they can invade local tissues or metastasize. Primary central nervous system fibrosarcomas are very aggressive neoplasms and generally have a poor prognosis. This tumor is either from sarcomatous transformation of a meningioma or arises de novo within the brain parenchyma. Our patient, a 48-year-old woman, who presented with progressive speech disorder over the period of 4 months, showed a left temporoparietal lesion with surrounding edema and local mass effect. Total surgical resection was achieved. Histopathology revealed classical fibrosarcoma features and secondary screening revealed no other distant lesion as diagnosis of primary brain fibrosarcoma was established. This case is deemed to be extremely rare because most reports claim that recurrence is within 6 months with poor prognosis; however, this patient is currently recurrence-free at 3 years. This would suggest of the possibility for a relook into this disease's course and recurrence rate when complete excision is achieved. Due to extreme rarity of these tumors, more comparative studies will be needed to improve the disease outcome.

3D chick embryo chorioallantoic membrane model as an in vivo model to study morphological and histopathological features of feline fibrosarcomas.

PubMed

Zabielska-Koczywąs, Katarzyna; Wojtkowska, Agata; Dolka, Izabella; Małek, Anna; Walewska, Magdalena; Wojtalewicz, Anna; Żbikowski, Artur; Lechowski, Roman

2017-06-26

The chick embryo chorioallantoic membrane (CAM) model is well described in human medicine as a cost-effective, easy to perform preclinical oncological model for observing pro- and antiangiogenic response, tumor biology and metastasis. The main objective of this article was to present the modification of the CAM assay in order to evaluate tumor growth from two feline fibrosarcoma cell lines (FFS1, FFS3) and describe their morphological and histopathological features. The authors described morphological and histopathological features of two feline fibrosarcoma cell lines (FFS1 and FFS3) grown on the CAM. Tumors from the FFS1 cell line showed high malignancy (grade III), while tumors from the FFS3 cell line were grade II. Proliferation markers (Ki-67 and PCNA) were determined and the positive correlation between PCNA and tumor grade (r = 0.8247; p < 0.001) was demonstrated, as opposed to Ki-67. The results obtained indicate that PCNA may be helpful to evaluate the tumor grade, better than Ki-67, for feline fibrosarcomas. However, further investigations of proliferation marker, in bigger number of feline spontaneous fibrosarcomas and feline fibrosarcomas grown on the CAM from different cell lines, are needed to confirm these observations.

The Role of XMRV, a Novel Xenotropic Murine Retrovirus, in Human Prostate Cancer

DTIC Science & Technology

2009-05-01

fibrosarcoma ),  HeLa   (cervical   carcinoma),   and...carcinoma),  TE671  (human  rhabdomyosarcoma),  2fTGH   cells  (human   fibrosarcoma ),  and  monitored  for  RT  release  for...cervical   carcinoma;   TE671   –   human   rhabdomyosarcoma;   2fTGH   –   human   fibrosarcoma ;  LNCaP  –

Fibrosarcoma of the ethmoid.

PubMed

Smith, M C; Soames, J V

1989-07-01

Fibrosarcoma may involve the ethmoid sinus by extension from the maxillary antrum or, more rarely, arise as a primary neoplasm. A case of a well differentiated primary fibrosarcoma of the ethmoid sinuses is reported which presented in a 24-year-old male. The tumour was treated by wide local resection. From a review of similar cases in the literature together with their treatment modalities and outcome, it is concluded that wide local resection is the treatment of choice.

Corneal fibrosarcoma in a cat.

PubMed

Strong, Travis D; Tangeman, Sarah; Ben-Shlomo, Gil; Haynes, Joseph; Allbaugh, Rachel A

2016-07-01

To present the clinicopathologic features of a Domestic Short-haired cat with spontaneous, intermediate-grade corneal fibrosarcoma, possibly secondary to chronic corneal irritation associated with a corneal sequestrum. A 12-year-old, spayed female Domestic Short-haired cat was evaluated for a slowly growing, pink, exophytic mass affecting the left cornea. The cat had presented 6 years previously for bilateral brown corneal sequestra, as well as 3 years previously for a small pale growth on the left cornea hypothesized to be an epithelial inclusion cyst and a corneal ulcer affecting the right eye. Incisional biopsy of the corneal mass indicated intermediate-grade corneal fibrosarcoma within the corneal stroma. Owing to the potential for malignant behavior, the left globe was enucleated. Routine systemic staging was performed prior to surgery with no evidence of metastasis. Definitive diagnosis of corneal fibrosarcoma was made through histopathologic examination of the incisional biopsy. There was an elevated mitotic index, indicating an intermediate-grade phenotype. Histopathology of the enucleated globe substantiated the initial findings, and complete tumor resection was confirmed. Subjacent to the corneal fibrosarcoma, there was a region of necrotic tissue suggestive of a corneal sequestrum. Six months after diagnosis and enucleation, the patient remained healthy with no signs of local spread or distant metastasis. To the authors' knowledge, this is the first documented case of a corneal fibrosarcoma in a cat. © 2016 American College of Veterinary Ophthalmologists.

Epidemiologic evidence for a causal relation between vaccination and fibrosarcoma tumorigenesis in cats.

PubMed

Kass, P H; Barnes, W G; Spangler, W L; Chomel, B B; Culbertson, M R

1993-08-01

Within the past 2 years, a putative causal relationship has been reported between vaccination against rabies and the development of fibrosarcomas at injection sites in cats. A retrospective study was undertaken, involving 345 cats with fibrosarcomas diagnosed between January 1991 and May 1992, to assess the causal hypothesis. Cats with fibrosarcomas developing at body locations where vaccines are typically administered (n = 185) were compared with controls (n = 160) having fibrosarcomas at locations not typically used for vaccination. In cats receiving FeLV vaccination within 2 years of tumorigenesis, the time between vaccination and tumor development was significantly (P = 0.005) shorter for tumors developing at sites where vaccines are typically administered than for tumors at other sites. Univariate analysis, adjusted for age, revealed associations between FeLV vaccination (odds ratio [OR] = 2.82; 95% confidence interval [CI] = 1.54 to 5.15), rabies vaccination at the cervical/interscapular region (OR = 2.09; 95% CI = 1.01 to 4.31), and rabies vaccination at the femoral region (OR = 1.83; 95% CI = 0.65 to 5.10) with fibrosarcoma development at the vaccination site within 1 year of vaccination. Multivariate analysis, adjusted for age and other vaccines, also revealed increased risks after FeLV (OR = 5.49; 95% CI = 1.98 to 15.24) and rabies (OR = 1.99; 95% CI = 0.72 to 5.54) vaccination.(ABSTRACT TRUNCATED AT 250 WORDS)

Sinonasal fibrosarcoma: analysis of the Surveillance, Epidemiology, and End Results database.

PubMed

Patel, Tapan D; Carniol, Eric T; Vázquez, Alejandro; Baredes, Soly; Liu, James K; Eloy, Jean Anderson

2016-02-01

Primary fibrosarcoma of the sinonasal region is an infrequently occurring malignant neoplasm. Fibrosarcomas are most commonly found in the extremities, with only 1% of fibrosarcomas reported in the head and neck region. This study analyzes the demographic, clinicopathologic, and survival characteristics of sinonasal fibrosarcoma (SNFS). The Surveillance, Epidemiology, and End Results (SEER) database (1973 to 2012) was queried for SNFS cases. Data were analyzed with respect to various demographic and clinicopathologic factors. Survival was analyzed using the Kaplan-Meier model. Fifty-one cases of fibrosarcoma were identified in the sinonasal region. The mean age at diagnosis was 54.5 years and the mean survival was 119.7 months. There was no gender predilection with a male-to-female ratio of 1.04:1. The maxillary sinus was the most common site of involvement (54.9%), followed by the nasal cavity (23.5%). Five-year survival analysis revealed an overall survival rate of 71.7%, disease-specific survival rate of 77.8%, and relative survival (RS) rate of 78.8%. Disease-specific survival was better among those treated with surgery (with [76.2%] or without [87.5%] adjuvant radiotherapy) than those treated with primary radiotherapy alone (33.3%) (p = 0.0069). SNFS is a rare entity. This study represents the largest series of SNFS to date. The mainstay of treatment for this tumor is surgical resection with or without radiotherapy. © 2015 ARS-AAOA, LLC.

[Surgical and chemotherapeutic treatment of fibrosarcoma in a cat].

PubMed

Odendaal, J S; Cronje, J D; Bastianello, S S

1983-09-01

Fibrosarcoma in a cat was repeatedly treated unsuccessfully by surgery and chemotherapy, which included drugs such as amethopterin sodium at very high dosages, vincristine sulphate and doxyrubicine hydrochloride.

Bilateral subcutaneous fibrosarcomas in a cat following feline parvo-, herpes- and calicivirus vaccination.

PubMed

De Man, Marc M G; Ducatelle, Richard V

2007-10-01

A crossbred cat developed a subcutaneous fibrosarcoma on the left side of the thorax at the site of previous administration of a feline parvo-, herpes- and calicivirus vaccine. A few months later the cat developed a second mass on the right side of the thorax after a booster vaccine had been administered at this site. This unique case of bilateral fibrosarcomas in a cat shortly after vaccination with parvo-, herpes- and caliciviruses suggests an individual disposition for the development of vaccine-associated sarcomas and a possible triggering of this type of pathological response which could have precipitated the development of the second tumour. To the authors' knowledge, this is the first case of vaccine-induced fibrosarcomas occurring bilaterally after injection of a feline parvo-, herpes- and calicivirus containing vaccine at different sides of the thorax.

Growth regulators in connective tissue. Systemic administration of an aortic extract inhibits tumor growth in mice.

PubMed Central

Eisenstein, R.; Schumacher, B.; Meineke, C.; Matijevitch, B.; Kuettner, K. E.

1978-01-01

A low-molecular-weight fraction prepared from extracts of bovine aorta inhibits the growth of a transplantable mammary tumor and a fibrosarcoma in mice when injected systemically. It also inhibits the growth of the fibrosarcoma in cell culture. The effect on the fibrosarcoma is much more marked than on the mammary tumor. Since the extract is more effective against the fibrosarcoma and is known to inhibit the growth of endothelial cells, it appears that the enhanced effect on this tumor is due to its activity on the endothelial cells of the host and the tumor cells themselves. The material injected is enriched in an antiproteinase we have previously isolated, which has anticollagneolytic activity and is presumed to be the effector molecule. Images Figure 1 Figure 2 PMID:645813

Radiotherapy and hyperthermia in the treatment of fibrosarcomas in the dog.

PubMed

Brewer, W G; Turrel, J M

1982-07-15

Ten dogs with oral or external nasal fibrosarcoma were treated sequentially with orthovoltage radiation and radiofrequency (RF)-induced hyperthermia. Total radiation doses ranged from 3,200 to 4,800 rad given in 8 to 12 fractions of 400 rad. Immediately after 2 to 4 radiation treatments, hyperthermia was given. Six oral fibrosarcomas were heated to 50 C for 30 sec, using a hand-held RF generator. Four nasomaxillary fibrosarcomas were heated to 43 C for 30 minutes, using a 500-kHz RF generator. Hyperthermia of 50 C resulted in tumor necrosis and infection in 3 dogs and fatal septicemia in 1 dog. Nine of 10 tumors responded to therapy. One year after therapy, 5 dogs were free of disease. Tumor regrowth occurred in 5 dogs. Mean time to tumor regrowth and mean survival time of all dogs were 343 and 398 days, respectively. The results suggested that sequential radiation-hyperthermia is an effective therapeutic regimen for canine fibrosarcoma. It was concluded that this modality not only may be beneficial in the treatment of canine tumors but may be useful for designing new therapeutic approaches to similar tumors in man.

Computed tomography characteristics of fibrosarcoma -- a histological subtype of feline injection-site sarcoma.

PubMed

Travetti, Olga; di Giancamillo, Mauro; Stefanello, Damiano; Ferrari, Roberta; Giudice, Chiara; Grieco, Valeria; Saunders, Jimmy H

2013-06-01

Feline injection-site sarcoma (FISS) may be a consequence of subcutaneous injection. In the present study, the medical records and the computed tomography (CT) features of 22 cats with a FISS, histopathological subtype fibrosarcoma, were used. The majority of the fibrosarcomas (45%) were located in the interscapular region. All fibrosarcomas, except one with mild enhancement, showed strong contrast uptake, characterised as ring (42%), heterogeneous (36%), homogeneous (9%), heterogeneous/ring (6.5%) or mixed heterogeneous/homogeneous enhancement (6.5%). The longest axis of the mass was in a cranio-caudal (68%) or dorso-ventral (32%) direction. The median volume calculated on CT was 7.57 cm(3). Common features were a marked local invasiveness of the musculature and heterogeneity of the tissue in the periphery of the neoplasia. When the fibrosarcoma was interscapular, performing an additional post-contrast scan with the forelimbs positioned caudally along the body, in addition to the standard protocol with the forelimbs extended cranially, allowed better evaluation of the actual relationship between the tumour and the surrounding tissues. The mean number of muscles involved with the tumour was 2.09 with extended and 1.95 with flexed forelimbs. When a lower number of structures was considered infiltrated through the double positioning, a less invasive surgical approach to underlying muscles and scapula was performed.

In vivo marking of spontaneous or vaccine-induced fibrosarcomas in the domestic house cat, using an adenoviral vector containing a bifunctional fusion protein, GAL-TEK.

PubMed

Marini, F C; Cannon, J P; Belmont, J W; Shillitoe, E J; Lapeyre, J N

1995-09-01

We evaluated the ability of a replication-deficient, recombinant adenoviral vector to transfer the bifunctional gene GAL-TEK, which expresses a marking/therapeutic gene product, to naturally occurring cat fibrosarcomas in situ. GAL-TEK contains an in-frame fusion of the bacterial LacZ gene for histochemical marking of tumors with beta-galactosidase (beta-Gal) and the HSV tk gene for enzyme-prodrug activation of the prodrug ganciclovir (GCV) to induce selective tumor cell killing. GAL-TEK bifunctional marking and cell killing activities were tested in vitro after adenoviral vector infection of HT1080 human fibrosarcoma cells. The tk activity of GAL-TEK is shown to be almost as potent as HSV tk to catalyze conversion of GCV to GCV nucleotides and promote selective cell killing. Using 8 cats with recurring 2.5-cm2 fibrosarcomas that either arose spontaneously or were induced by vaccine, we determined experimentally the administration routes and times required for optimum GAL-TEK gene transfer by beta-Gal histological staining and reverse transcriptase polymerase chain reaction to the multiple compartments of the growing fibrosarcomas consonant with minimizing collateral infection of neighboring tissues and other unwanted side effects.

Feline fibrosarcoma: perioperative management.

PubMed

Davis, Kechia M; Hardie, Elizabeth M; Lascelles, B Duncan X; Hansen, Bernie

2007-12-01

Aggressive and complete surgical excision is the treatment of choice for fibrosarcomas in cats. Thorough preoperative planning and meticulous surgical technique are necessary for optimal cosmetic, functional, and oncologic outcome. Perioperative pain management with an emphasis on preemptive analgesia and multimodal analgesia is essential to minimize patient morbidity.

Vaccine-associated fibrosarcoma in a cat.

PubMed

Martin, Melanie

2003-08-01

An 8-year-old, spayed, female domestic shorthair was diagnosed with a vaccine-associated fibrosarcoma and treated with full course radiation therapy, aggressive surgery, and postoperative chemotherapy. Histopathologic examination confirmed that excision of the tumor was complete. The cat was doing well 278 days after initial presentation.

Bilateral uveal metastasis of a subcutaneous fibrosarcoma in a cat.

PubMed

Mowat, Freya M; Langohr, Ingeborg M; Bilyk, Olenka; Koterbay, Amy; Pierce, Kenneth E; Petersen-Jones, Simon M

2012-11-01

A 6-year-old neutered male domestic short-haired cat was presented to the Comparative Ophthalmology service at Michigan State University with a 3-week history of decreased appetite and redness of the left eye. The left forelimb had been removed 15 months previously because of the presence of a subcutaneous fibrosarcoma. In the left globe, a large iridal mass was associated with increased intraocular pressure and retinal detachment. A smaller mass involving the right iris was also present. Imaging revealed a 2-cm mass in the left caudodorsal lung lobe, and abdominal ultrasound showed multifocal bilateral renal masses. Aspirates of these masses were nondiagnostic. The left globe was removed for palliative reasons, and histopathology showed that fibrosarcoma was infiltrating the iris, choroid, and optic nerve. Despite systemic chemotherapy with doxorubicin, the animal died 4 months after initial presentation. Histopathology confirmed highly angioinvasive metastatic fibrosarcoma also in the right uveal tract, the lungs, and both kidneys. © 2012 American College of Veterinary Ophthalmologists.

Fibrosarcoma of the urinary bladder in a cat

PubMed Central

Capasso, Angelo; Raiano, Vera; Sontuoso, Antonio; Olivero, Daniela

2015-01-01

Case summary A 5-year-old female spayed domestic shorthair cat was presented with haematuria, pollakiuria and stranguria of 2 months’ duration, and a firm non-painful mass in the urinary bladder was palpated. Abdominal radiographs showed thickening and irregular cranial margins of the urinary bladder wall. Abdominal ultrasound showed a vascularised mass of mixed echogenicity almost entirely occupying the urinary bladder lumen. During explorative laparotomy, the mass appeared pedunculated and was totally excised. Histopathology was characterised by infiltration of the mucosal, submucosal and muscular layers by proliferated atypical mesenchymal cells; immunochemistry confirmed the diagnosis of fibrosarcoma. The cat was discharged with normal urination 5 days after surgery. The owner declined any imaging follow-up but reported the cat to be free of any clinical signs at 16 months after surgery. Relevance and novel information To the best of our knowledge, this is the first case of primary fibrosarcoma of the urinary bladder in the cat. Fibrosarcoma should be included in the differential diagnosis of urinary bladder neoplasia. PMID:28491352

Fibrosarcoma of the urinary bladder in a cat.

PubMed

Capasso, Angelo; Raiano, Vera; Sontuoso, Antonio; Olivero, Daniela; Greci, Valentina

2015-01-01

A 5-year-old female spayed domestic shorthair cat was presented with haematuria, pollakiuria and stranguria of 2 months' duration, and a firm non-painful mass in the urinary bladder was palpated. Abdominal radiographs showed thickening and irregular cranial margins of the urinary bladder wall. Abdominal ultrasound showed a vascularised mass of mixed echogenicity almost entirely occupying the urinary bladder lumen. During explorative laparotomy, the mass appeared pedunculated and was totally excised. Histopathology was characterised by infiltration of the mucosal, submucosal and muscular layers by proliferated atypical mesenchymal cells; immunochemistry confirmed the diagnosis of fibrosarcoma. The cat was discharged with normal urination 5 days after surgery. The owner declined any imaging follow-up but reported the cat to be free of any clinical signs at 16 months after surgery. To the best of our knowledge, this is the first case of primary fibrosarcoma of the urinary bladder in the cat. Fibrosarcoma should be included in the differential diagnosis of urinary bladder neoplasia.

Vaccine-associated fibrosarcoma in a cat

PubMed Central

Martin, Melanie

2003-01-01

An 8-year-old, spayed, female domestic shorthair was diagnosed with a vaccine- associated fibrosarcoma and treated with full course radiation therapy, aggressive surgery, and postoperative chemotherapy. Histopathologic examination confirmed that excision of the tumor was complete. The cat was doing well 278 days after initial presentation. PMID:13677599

Recurrent EML4-NTRK3 fusions in infantile fibrosarcoma and congenital mesoblastic nephroma suggest a revised testing strategy.

PubMed

Church, Alanna J; Calicchio, Monica L; Nardi, Valentina; Skalova, Alena; Pinto, Andre; Dillon, Deborah A; Gomez-Fernandez, Carmen R; Manoj, Namitha; Haimes, Josh D; Stahl, Joshua A; Dela Cruz, Filemon S; Tannenbaum-Dvir, Sarah; Glade-Bender, Julia L; Kung, Andrew L; DuBois, Steven G; Kozakewich, Harry P; Janeway, Katherine A; Perez-Atayde, Antonio R; Harris, Marian H

2018-03-01

Infantile fibrosarcoma and congenital mesoblastic nephroma are tumors of infancy traditionally associated with the ETV6-NTRK3 gene fusion. However, a number of case reports have identified variant fusions in these tumors. In order to assess the frequency of variant NTRK3 fusions, and in particular whether the recently identified EML4-NTRK3 fusion is recurrent, 63 archival cases of infantile fibrosarcoma, congenital mesoblastic nephroma, mammary analog secretory carcinoma and secretory breast carcinoma (tumor types that are known to carry recurrent ETV6-NTRK3 fusions) were tested with NTRK3 break-apart FISH, EML4-NTRK3 dual fusion FISH, and targeted RNA sequencing. The EML4-NTRK3 fusion was identified in two cases of infantile fibrosarcoma (one of which was previously described), and in one case of congenital mesoblastic nephroma, demonstrating that the EML4-NTRK3 fusion is a recurrent genetic event in these related tumors. The growing spectrum of gene fusions associated with infantile fibrosarcoma and congenital mesoblastic nephroma along with the recent availability of targeted therapies directed toward inhibition of NTRK signaling argue for alternate testing strategies beyond ETV6 break-apart FISH. The use of either NTRK3 FISH or next-generation sequencing will expand the number of cases in which an oncogenic fusion is identified and facilitate optimal diagnosis and treatment for patients.

Nonepithelial tumors of the nasal cavity, paranasal sinuses, and nasopharynx. A clinicopathologic study. VI. Fibrous tissue tumors (fibroma, fibromatosis, fibrosarcoma).

PubMed

Fu, Y S; Perzin, K H

1976-06-01

In a study of 256 nonepithelial neoplasms involving the nasal cavity, paranasal sinuses, and nasopharynx, 23 lesions were classified as fibrous tissue tumors, including four cases of "fibroma", six of fibromatosis, and thirteen of fibrosarcoma. The clinical findings associated with these lesions are described, their histologic features illustrated, results of therapy presented and clinicopathologic correlations made. The "fibromas" presented a small localized nodules. None recurred after local excision. Fibromatosis, a locally aggressive tumor, does not metastasize, but may cause considerable morbidity or even death due to local infiltration which may be difficult to control surgically. Fibrosarcoma may cause death either by local infiltration or by metastasis, but has a better prognosis than most other sarcomas of this region. We recommend that a large en block resection be performed initially for fibromatosis and fibrosarcoma growing in this area, after the diagnosis has been made by biopsy. In this series, including patients who had more than one operation, recurrent tumor was seen following 10 of 12 limited local excisions performed for fibromatosis and fibrosarcoma, but in only one of 13 patients after a large bloc resection. The problems involved in histologically differentiating fibrous tissue tumors from other lesions are discussed. A patient with the rare syndrome of multicentric fibromatosis with spontaneous regression of lesions is presented.

Ameloblastic fibrosarcoma: Report of a case

PubMed Central

Akinyamoju, Akindayo O; Olusanya, Adeola A; Adeyemi, Bukola F; Kolude, B

2013-01-01

Ameloblastic fibrosarcoma (AFS) is a rare odontogenic malignancy with benign epithelial and malignant ectomesenchymal components. About 66 cases have been reported in the medical literature. We therefore report an additional case as well as a review of literature to add to the existing knowledge on this rare lesion. PMID:24574665

Low-grade fibrosarcoma of the anterior skull base: endoscopic resection and repair.

PubMed

Kuhn, Frederick A; Javer, Amin R

2003-01-01

Fibrosarcomas of the paranasal sinuses and skull base are uncommon tumors. Traditionally, "open approach" surgery remains the mainstay for treatment of choice for these tumors. A 49-year-old man underwent resection of a right anterior skull base fibrosarcoma using the endoscopic approach. Close follow-up using both endoscopic and imaging methods over a period of four years has revealed a well-healed skull base with no evidence of recurrence. Significant resistance exists at present for such a technique to deal with malignant diseases of the head and neck but results from advanced centers continue to prove that this may be a technique worth mastering and improving on.

Near triploidy in a feline fibrosarcoma.

PubMed

Mayr, B; Eschborn, U; Kalat, M

1991-10-01

A seven-year-old male cat developed a subcutaneous fibrosarcoma. The numerical cytogenetic evaluation of the tumour revealed the presence of 69.2% of cells in the near-triploid chromosome range between 51 and 64. The copy numbers of the different chromosomes were widely distributed from monosomies up to heptasomies. Two giant chromosomes were regularly present.

[Fibrosarcoma of the nasal surface in a cat--cosmetically pleasing healing after surgical removal].

PubMed

Neumann, W; Wittker, J; Bahnemann, R

1990-06-01

In a seven year old male domestic cat diagnosis, therapy and healing of a nasal fibrosarcoma is described. After two surgical treatments no recurrence was seen in a time period of 10 months. Even with this unfavourable localization of the tumor a functionally and cosmetically satisfactory result was achieved.

Destructive Fibrosarcoma of the Maxillary Sinus.

PubMed

Ekinci, Adnan; Karataş, Duran; Yetiş, Abdurrahman; Erenler, Behice Hande; Ozcan, Muge

2018-05-01

Paranasal fibrosarcoma of nasal cavity and paranasal sinuses is a very rare malignant tumor. It is usually presented with nasal obstruction and epistaxis. In this clinical report, clinical symptoms, pathogenesis, and treatment principles of a paranasal fibrosarcoma originating from the right maxillary sinus and obstructing the right nasal passage are discussed.A 55-year-old male patient was admitted to the authors clinic with complaints of nasal obstruction and epistaxis lasting for 2 years. Anterior rhinoscopy revealed a mass lesion which obstructed the right nasal passage and caused frequent epistaxis. An opacity consistent with soft tissue lesion which was originated from the right maxillary sinus and filled the right nasal passage was observed in paranasal tomography. Magnetic resonance imaging revealed that the mass lesion was contrasted. Tumor was seen to erode orbital floor, and lateral and anterior walls of the maxillary sinus. Biopsy result was reported as papilloma. The patient was treated with Denker approach as anterior wall of the maxillary sinus was eroded by the tumor lesion and the mass lesion was excised. The patient received postoperative radiotherapy as pathological diagnosis was reported as paranasal fibrosarcoma.

Inhibitory effects of Indigofera aspalathoides on 20-methylcholanthrene-induced chemical carcinogenesis in rats.

PubMed

Kumar, S Selva; Karrunakaran, C M; Rao, M R K; Balasubramanian, M P

2011-01-11

The anticancer and antioxidant effects of the aqueous extract of Indigofera aspalathoides on 20-methylcholanthrene (20-MCA) induced fibrosarcoma were investigated in male albino rats. The rats were divided into four different groups, each group consisting of six animals. Group I animals were served as normal control, Group II animals were fibrosarcoma-bearing animals after the incubation period, Group III animals were fibrosarcoma-bearing animals, treated with aqueous extract of I. aspalathoides intraperitoneally at a dose of 250 mg/kg b.w. for 30 days and Group IV animals were administered with the aqueous extract of I. aspalathoides alone, at a dose of 250 mg/kg b.w. for 30 days, served as drug control animals. After the experimental period, all the rats were weighed and killed by cervical decapitation. The serum was separated from the blood for analysis. The weights of the liver and the kidneys were noted. The fibrosarcoma was proved by pathological examinations. The liver and kidney tissues were excised and then homogenized in an ice-cold buffer. These tissues were used for biochemical analysis. The activities of antioxidant enzymes, e.g. catalase (CAT), glutathione peroxidase (GPx) and superoxide dismutase (SOD), in blood serum, liver, and kidney of control and experimental animals, respectively, have been reported. The present observations suggested that the aqueous extract of I. aspalathoides treatment enhanced the recovery from 20-MCA-induced fibrosarcoma due to its antioxidants and antineoplastic properties.

Inhibitory effects of Indigofera aspalathoides on 20-methylcholanthrene-induced chemical carcinogenesis in rats

PubMed Central

Kumar, S. Selva; Karrunakaran, C. M.; Rao, M. R. K.; Balasubramanian, M. P.

2011-01-01

Background: The anticancer and antioxidant effects of the aqueous extract of Indigofera aspalathoides on 20-methylcholanthrene (20-MCA) induced fibrosarcoma were investigated in male albino rats. Materials and Methods: The rats were divided into four different groups, each group consisting of six animals. Group I animals were served as normal control, Group II animals were fibrosarcoma-bearing animals after the incubation period, Group III animals were fibrosarcoma-bearing animals, treated with aqueous extract of I. aspalathoides intraperitoneally at a dose of 250 mg/kg b.w. for 30 days and Group IV animals were administered with the aqueous extract of I. aspalathoides alone, at a dose of 250 mg/kg b.w. for 30 days, served as drug control animals. After the experimental period, all the rats were weighed and killed by cervical decapitation. The serum was separated from the blood for analysis. The weights of the liver and the kidneys were noted. The fibrosarcoma was proved by pathological examinations. The liver and kidney tissues were excised and then homogenized in an ice-cold buffer. These tissues were used for biochemical analysis. Results: The activities of antioxidant enzymes, e.g. catalase (CAT), glutathione peroxidase (GPx) and superoxide dismutase (SOD), in blood serum, liver, and kidney of control and experimental animals, respectively, have been reported. Conclusion: The present observations suggested that the aqueous extract of I. aspalathoides treatment enhanced the recovery from 20-MCA-induced fibrosarcoma due to its antioxidants and antineoplastic properties. PMID:21297921

Adjuvant immunotherapy of feline fibrosarcoma with recombinant feline interferon-omega.

PubMed

Hampel, Verena; Schwarz, Bianca; Kempf, Christine; Köstlin, Roberto; Schillinger, Ulrike; Küchenhoff, Helmut; Fenske, Nora; Brill, Thomas; Hirschberger, Johannes

2007-01-01

Recombinant feline interferon-omega (rFeIFN-omega) was tested as a treatment option for cats with fibrosarcoma to assess safety and feasibility. Treatment with rFeIFN-omega in cats with fibrosarcoma is safe and feasible. Twenty domestic cats. In an open-labeled uncontrolled clinical trial 12 injections of 1 x 10(6) U/kg rFeIFN-omega were administered over a 5-week period: the 1st through 4th injections were given intratumorally, and the 5th through 12th injections were administered subcutaneously at the tumor excision site. Wide surgical excision of the tumors was carried out after the 4th injection and before the 5th injection of rFeIFN-omega. A Common Terminology Criteria for Adverse Events (CTCAE) analysis was conducted. Flow cytometry of fibrosarcoma cells after incubation with rFeIFN-omega and recombinant feline interferon-gamma was performed to assess the biological effect of rFeIFN-omega. Changes in blood cell count, increases in serum aspartate-amino-transferase activity, serum bilirubin concentration, serum creatinine and serum electrolyte concentrations, weight loss, anorexia, increased body temperature, and reduced general condition were observed but were mostly minor (grade 1 and 2) and self limiting. Eosinophilia (P = .025), neutropenia (P = .021), and weight loss (P < .001) were statistically correlated with rFeIFN-omega-treatment (analysis of parameters before treatment and after 3 injections of rFeIFN-omega). Flow cytometry of 5 unrelated feline fibrosarcoma cell lines showed increased expression of major histocompatibility complex (MHC) class I molecules (P = .026) in response to in vitro incubation with rFeIFN-omega, whereas expression of MHC class II molecules was not affected significantly. RFeIFN-omega for the treatment of feline fibrosarcoma is safe, well tolerated, and can be easily performed in practice. To assess the efficacy of the treatment, it should be tested in a placebo-controlled trial.

Trisomy D1, marker F1: new cytogenetic findings in two cases of feline fibrosarcoma.

PubMed

Mayr, B; Hofstadler, E; Schleger, W; Reifinger, M; Eisenmenger, E

1994-04-01

An 11-year-old female cat and a 12-year-old male cat developed fibrosarcomas. Trisomy D1 was observed in a high percentage (20%) of the tumour cells of the female patient while a large marker chromosome F1 was present in 25% of the tumour cells of the male patient.

Cytogenetic variation between four cases of feline fibrosarcoma.

PubMed

Mayr, B; Bockstahler, B; Loupal, G; Reifinger, M; Schleger, W

1996-11-01

Short term cultures of four feline fibrosarcomas were analysed cytogenetically. There was marked genetic heterogeneity between the four cats, each showing a different clonal abnormality. The aberrations detected were one deleted B2, one marker F1 and two reciprocal translocations, t (A2q; E3q) and t (A1q; B4p).

Tumor-associated erythrocytosis in a dog with nasal fibrosarcoma.

PubMed

Couto, C G; Boudrieau, R J; Zanjani, E D

1989-01-01

Erythrocytosis (hematocrit, 79%) was diagnosed in an 8-year-old, neutered female, mixed-breed dog with an intranasal fibrosarcoma. Both serum and tumor erythropoietin (Ep) activities were elevated, as determined by the polycythemic exhypoxic mouse model, and the Ep activity was neutralized in that model by rabbit anti-Ep antibodies. Tumor resection normalized the hematocrit.

[Sclerosing epithelioid fibrosarcoma of the paravertebral column. Case report and literature review].

PubMed

Puerta Roldán, Patricia; Rodríguez Rodríguez, Rodrigo; Bagué Rossell, Silvia; de Juan Delago, Manel; Molet Teixidó, Joan

2013-01-01

Sclerosing epithelioid fibrosarcoma (SEF) is a rare variant of low-grade fibrosarcoma, with specific histological and immunohistochemical features and a poor prognosis. We report a case of SEF of the paravertebral column in a 49-year old male who presented a paraspinal mass with extension into the L4-L5 neural foramen and invasion of the L5 nerve root. Histology of the tumourectomy specimen and its immunohistochemical study led to the diagnosis of SEF. This case was particularly unusual due to its paravertebral column location and, despite its low grade, illustrates the malignant potential of SEF. Copyright © 2012 Sociedad Española de Neurocirugía. Published by Elsevier España. All rights reserved.

Fibrosarcoma adjacent to the site of microchip implantation in a cat.

PubMed

Daly, Meighan K; Saba, Corey F; Crochik, Sonia S; Howerth, Elizabeth W; Kosarek, Carrie E; Cornell, Karen K; Roberts, Royce E; Northrup, Nicole C

2008-04-01

A 14-year-old spayed female domestic shorthair cat presented with an interscapular mass. A computed tomography scan, biopsy, and histological examination revealed a fibrosarcoma adjacent to a pet identification microchip. Because the cat was previously vaccinated at this site, it is not possible to establish definitive causation of the fibrosarcoma, but this is the first report of a tumor in the vicinity of a microchip in a cat. Microchip-associated tumors have been reported in rodents and dogs. Veterinarians should be aware that because inflammation may predispose felines to tumor formation, separation and observation of vaccination and implantation sites are indicated. Adherence to American Association of Feline Practitioners (AAFP) vaccination guidelines and monitoring of microchip implantation sites are recommended.

Vaccine-associated fibrosarcoma with keloidal differentiation in a cat.

PubMed

Gumber, Sanjeev; Wakamatsu, Nobuko

2011-09-01

A 6-year-old Domestic Shorthair cat was presented with a history of subcutaneous mass of the lateral left hind limb. The subcutaneous mass developed over a period of approximately 16 months subsequent to administration of Feline leukemia virus vaccines. Based on the histopathological and immunohistochemical examination, the subcutaneous mass was diagnosed as vaccine-associated fibrosarcoma with keloidal differentiation.

Hepatic fibrosarcoma incarcerated in a peritoneopericardial diaphragmatic hernia in a cat.

PubMed

Linton, Michael; Tong, Lydia; Simon, Adrian; Buffa, Eugene; McGregor, Ross; Labruyére, Julien; Foster, Darren

2016-01-01

A 14-year-old, female neutered domestic shorthair presented for dyspnoea. Thoracic ultrasonography and radiography showed that a heterogeneous mass was present within the pericardial sac, and the mass continued caudally with the mesenteric fat. On CT, the outline of the diaphragm was not continuous and there was an obvious defect with diaphragmatic thickening present at the mid-level of the liver. A pleural effusion and a small-volume pericardial effusion were also present. A ventral midline coeliotomy and median sternotomy revealed a 5 × 6 × 7 cm firm, irregular, tan-coloured soft tissue mass within the pericardial sac attached to both the diaphragmatic defect and liver. The mass was carefully dissected away from the heart and the diaphragmatic defect was repaired with primary closure. Postoperatively, the cat had a persistent pneumothorax that required continuous pleural suction for 41 h. The cat died 44 h postoperatively. Histopathology and immunohistochemistry confirmed the mass to be a hepatic fibrosarcoma incarcerated in a peritoneopericardial diaphragmatic hernia (PPDH). This is the first reported case of metaplastic transformation of liver into a sarcoma in a cat with PPDH. In addition, hepatic fibrosarcoma is a rarely reported location for fibrosarcoma in this species.

Ocular metastasis of a vaccine-associated fibrosarcoma in a cat.

PubMed

Cohen, M; Sartin, E A; Whitley, E M; Whitley, R D; Smith, A N; Brawner, W R; Henderson, R; Behrend, E N

2003-12-01

A 6-year-old, neutered male domestic shorthair cat was evaluated for a recurrent vaccine-associated fibrosarcoma. The cat had three excisions of the tumour prior to presentation and was referred for radiation therapy. Ten months following treatment with radiation therapy, the cat was presented again for a cloudy appearance to the eye. An exenteration was performed, and biopsy revealed fibrosarcoma. At the same time, two discrete pulmonary nodules were identified on thoracic radiographs. Two doses of doxorubicin (20 mg/m(2)) and cyclophosphamide (100 mg/m(2)) were administered intravenously 3 weeks apart. Despite treatment, the pulmonary nodule doubled in size. This case represents the first antemortem report of ocular metastasis of a vaccine-associated sarcoma and supports the highly aggressive nature of these tumours.

A rare sinonasal neoplasm: fibrosarcoma.

PubMed

Bercin, Sami; Muderris, Togay; Kırıs, Muzaffer; Kanmaz, Alper; Kandemir, Olcay

2011-05-01

Sinonasal fibrosarcoma is an infrequently occurring malignant neoplasm. It usually presents with nasal obstruction and epistaxis, as do other sarcomas in this region. The final diagnosis is based on the histopathologic and immunohistochemical examination. We report a case involving a 47-year-old woman with a 2-year history of left nasal obstruction and proptosis, as well as diplopia for the 2 months preceding her visit. Computed tomography and magnetic resonance imaging showed a neoplasm occupying the left nasal cavity, ethmoid sinuses, and bilateral frontal sinuses. The neoplasm also was eroding the medial wall of the maxillary sinus, the lamina papyracea, the cribriform plate, and the anterior wall of the frontal sinus. Complete removal of the tumor was achieved both endoscopically and through a Lynch incision. Sinonasal fibrosarcoma was found on histopathologic examination.

Inverted papilloma-like sinonasal epithelial hyperplasia, overshadowing underlying sinonasal fibrosarcoma: a diagnostic pitfall.

PubMed

Maly, Alexander; Maly, Bella; Eliashar, Ron; Doviner, Victoria

2006-01-01

Proliferating invaginations of the sinonasal epithelium, simulating inverted papillomas, have been mentioned once in the literature as a reactive phenomenon overlying sinonasal fibrosarcomas. These proliferations may be so marked as to make the distinction from inverted papilloma virtually impossible. The possible result is that the examining pathologist's attention might be drawn exclusively to the epithelial component, thus causing him to overlook, especially in a small biopsy, a rather bland but distinctive sarcomatoid component which is located underneath. We report such a case of marked endophytic proliferation of sinonasal epithelium which was interpreted, in the preoperative biopsy, as an inverted papilloma with dense fibrous stroma which later, in the surgical specimen, was found to be a part of a submucosal fibrosarcoma. The diagnostic pitfall is discussed.

Fibrosarcoma in the distal radius and carpus of a four-year-old Persian.

PubMed

Cook, J L; Turk, J R; Tomlinson, J L; Corwin, L A; Shaw, D C

1998-01-01

A four-year-old Persian was presented for evaluation of a nonweight-bearing, left forelimb lameness. Radioulnar and pancarpal osteolysis with minimal periosteal reaction were seen on radiographs of the antebrachium. Cytological examinations of fine-needle aspirates and impression smears were suggestive of sarcoma. After forequarter amputation, histopathological examination provided a diagnosis of fibrosarcoma with axillary lymph-node metastasis.

Electrochemical treatment of mouse and rat fibrosarcomas with direct current

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chou, C.K.; McDougall, J.A.; Ahn, C.

1997-03-01

Electrochemical treatment (ECT) of cancer utilizes direct current to produce chemical changes in tumors. ECT has been suggested as an effective alternative local cancer therapy. However, a methodology is not established, and mechanisms are not well studied. In vivo studies were conducted to evaluate the effectiveness of ECT on animal tumor models. Radiation-induced fibrosarcomas were implanted subcutaneously in 157 female C3H/HeJ mice. Larger rat fibrosarcomas were implanted on 34 female Fisher 344 rats. When the spheroidal tumors reached 10 mm in the mice, two to five platinum electrodes were inserted into the tumors at various spacings and orientations. Ten ratsmore » in a pilot group were treated when their ellipsoidal tumors were about 25 mm long; electrode insertion was similar to the later part of the mouse study; i.e., two at the base and two at the center. A second group of 24 rats was treated with six or seven electrodes when their tumors were about 20 mm long; all electrodes were inserted at the tumor base. Of the 24 rats, 12 of these were treated once, 10 were treated twice, and 2 were treated thrice. All treated tumors showed necrosis and regression for both mice and rats; however, later tumor recurrence reduced long-term survival. When multiple treatments were implemented, the best 3 month mouse tumor cure rate was 59.3%, and the best 6 month rat tumor cure rate was 75.0%. These preliminary results indicate that ECT is effective on the radiation-induced fibrosarcoma (RIF-1) mouse tumor and rat fibrosarcoma. The effectiveness is dependent on electrode placement and dosage.« less

Immunomodulatory properties of silver nanoparticles contribute to anticancer strategy for murine fibrosarcoma

PubMed Central

Chakraborty, Biswajit; Pal, Ramkrishna; Ali, Mohammed; Singh, Leichombam Mohindro; Shahidur Rahman, Dewan; Kumar Ghosh, Sujit; Sengupta, Mahuya

2016-01-01

The use of nanotechnology in nanoparticle-based cancer therapeutics is gaining impetus due to the unique biophysical properties of nanoparticles at the quantum level. Silver nanoparticles (AgNPs) have been reported as one type of potent therapeutic nanoparticles. The present study is aimed to determine the effect of AgNPs in arresting the growth of a murine fibrosarcoma by a reductive mechanism. Initially, a bioavailability study showed that mouse serum albumin (MSA)-coated AgNPs have enhanced uptake; therefore, toxicity studies of AgNP-MSA at 10 different doses (1–10 mg/kg b.w.) were performed in LACA mice by measuring the complete blood count, lipid profile and histological parameters. The complete blood count, lipid profile and histological parameter results showed that the doses from 2 to 8 mg (IC50: 6.15 mg/kg b.w.) sequentially increased the count of leukocytes, lymphocytes and granulocytes, whereas the 9- and 10-mg doses showed conclusive toxicity. In an antitumor study, the incidence and size of fibrosarcoma were reduced or delayed when murine fibrosarcoma groups were treated by AgNP-MSA. Transmission electron micrographs showed that considerable uptake of AgNP-MSA by the sentinel immune cells associated with tumor tissue and a morphologically buckled structure of the immune cells containing AgNP-MSA. Because the toxicity studies revealed a relationship between AgNPs and immune function, the protumorigenic cytokines TNF-α, IL-6 and IL-1β were also assayed in AgNP-MSA-treated and non-treated fibrosarcoma groups, and these cytokines were found to be downregulated after treatment with AgNP-MSA. PMID:25938978

Characteristics of a Virus Isolated from a Feline Fibrosarcoma

PubMed Central

McKissick, G. E.; Lamont, P. H.

1970-01-01

A virus was isolated from a radioresistant feline fibrosarcoma. It induced multi-nucleated giant-cell formation and lysis in a cell line derived from a canine fibro-sarcoma, which was used to characterize the virus. End-point titrations in these cells required 28 days. The virus was sensitive to ether and heat and was destroyed at pH 3. Replication was not inhibited by 5-bromodeoxyuridine. Electron microscopy revealed assembly by a budding process from the plasma membrane of infected cells. The average diameter of the virion was 106 nm. Intracisternal particles with an average diameter of 45 nm were present within infected cells. In two instances secondary monolayers of feline renal cells underwent morphological transformation after inoculation of the virus. The two strains of transformed cells are now in continuous culture and do not yield infectious virus. Images PMID:4194169

Fibrosarcoma of the mandible following supravoltage irradiation. Report of a case.

PubMed

Moloy, P J; Kowal, K A; Siegel, W M

1989-10-01

Supravoltage irradiation is commonly thought not to be carcinogenic. Several recent studies question this concept, as does our case report. A 50-year-old woman with stage 1 squamous carcinoma of the left side of the tongue was treated in 1973 with 73 Gy of supravoltage irradiation. Twelve years later a painful, ulcerated lesion that eventually was shown to be fibrosarcoma developed in the contralateral mandible. The fibrosarcoma in this case fulfills all criteria for diagnosing radiation-induced neoplasia and demonstrates that supravoltage irradiation, like other forms of irradiation, can cause malignancy. The occasional occurrence of sarcoma should be recalled during follow-up of patients treated with supravoltage radiation. Similarly, the possibility of radiation-induced tumors should be considered in planning treatment for younger patients with tumors that can be treated equally well by surgery or irradiation.

Hepatic fibrosarcoma incarcerated in a peritoneopericardial diaphragmatic hernia in a cat

PubMed Central

Linton, Michael; Tong, Lydia; Simon, Adrian; Buffa, Eugene; McGregor, Ross; Labruyére, Julien; Foster, Darren

2016-01-01

Case summary A 14-year-old, female neutered domestic shorthair presented for dyspnoea. Thoracic ultrasonography and radiography showed that a heterogeneous mass was present within the pericardial sac, and the mass continued caudally with the mesenteric fat. On CT, the outline of the diaphragm was not continuous and there was an obvious defect with diaphragmatic thickening present at the mid-level of the liver. A pleural effusion and a small-volume pericardial effusion were also present. A ventral midline coeliotomy and median sternotomy revealed a 5 × 6 × 7 cm firm, irregular, tan-coloured soft tissue mass within the pericardial sac attached to both the diaphragmatic defect and liver. The mass was carefully dissected away from the heart and the diaphragmatic defect was repaired with primary closure. Postoperatively, the cat had a persistent pneumothorax that required continuous pleural suction for 41 h. The cat died 44 h postoperatively. Histopathology and immunohistochemistry confirmed the mass to be a hepatic fibrosarcoma incarcerated in a peritoneopericardial diaphragmatic hernia (PPDH). Relevance and novel information This is the first reported case of metaplastic transformation of liver into a sarcoma in a cat with PPDH. In addition, hepatic fibrosarcoma is a rarely reported location for fibrosarcoma in this species. PMID:28491416

Fibrosarcoma arising at the site of a retained surgical sponge in a cat.

PubMed

Haddad, Jamie L; Goldschmidt, Michael H; Patel, Reema T

2010-06-01

An 8-year-old female spayed domestic shorthair cat had an abdominal mass palpated as an incidental finding on physical examination. Cytologic findings in ultrasound-guided fine-needle aspirates of the mass were most compatible with a sarcoma, with abundant mineralized material and mixed inflammation. The mass was removed surgically and on gross examination was white-tan, firm, associated with the mesentery, and when transected contained a gauze sponge in its center. On histopathologic examination, an area of central necrosis with mineralization and numerous refractile fibers consistent with sponge material was surrounded by dense fibrous connective tissue (gossypiboma). Within the connective tissue was a population of highly pleomorphic spindle cells consistent with a fibrosarcoma. Immunohistochemically, most neoplastic cells stained strongly positive for vimentin and a low number of cells were positive for smooth muscle actin. The results were consistent with a fibrosarcoma arising at the site of a retained surgical sponge. At a follow-up visit 2 months postoperatively, ultrasonographic and cytologic evidence of metastasis was found in the spleen and mesentery. To our knowledge, this is the first report of malignant transformation at the site of a retained surgical sponge in a cat and the first report of a fibrosarcoma arising within a gossypiboma in a domestic animal.

Gossypol inhibition of mitosis, cyclin D1 and Rb protein in human mammary cancer cells and cyclin-D1 transfected human fibrosarcoma cells.

PubMed Central

Ligueros, M.; Jeoung, D.; Tang, B.; Hochhauser, D.; Reidenberg, M. M.; Sonenberg, M.

1997-01-01

The antiproliferative effects of gossypol on human MCF-7 mammary cancer cells and cyclin D1-transfected HT-1060 human fibrosarcoma cells were investigated by cell cycle analysis and effects on the cell cycle regulatory proteins Rb and cyclin D1. Flow cytometry of MCF-7 cells at 24 h indicated that 10 microM gossypol inhibited DNA synthesis by producing a G1/S block. Western blot analysis using anti-human Rb antibodies and anti-human cyclin D1 antibodies in MCF-7 cells and high- and low-expression cyclin D1-transfected fibrosarcoma cells indicated that, after 6 h exposure, gossypol decreased the expression levels of these proteins in a dose-dependent manner. Gossypol also decreased the ratio of phosphorylated to unphosphorylated Rb protein in human mammary cancer and fibrosarcoma cell lines. Gossypol (10 microM) treated also decreased cyclin D1-associated kinase activity on histone H1 used as a substrate in MCF-7 cells. These results suggest that gossypol might suppress growth by modulating the expression of cell cycle regulatory proteins Rb and cyclin D1 and the phosphorylation of Rb protein. Images Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 PMID:9218727

Structure of the c-Ki-ras gene in a rat fibrosarcoma induced by 1,8-dinitropyrene.

PubMed Central

Tahira, T; Hayashi, K; Ochiai, M; Tsuchida, N; Nagao, M; Sugimura, T

1986-01-01

Restriction enzyme maps were made of the region around exons 1 and 2 of activated c-Ki-ras of a fibrosarcoma (1,8-DNP2) induced in a rat by 1,8-dinitropyrene. Nucleotide sequence analysis revealed that activated c-Ki-ras shows a G----T transversion in codon 12 and consequently encodes cysteine instead of glycine in normal rat c-Ki-ras. PMID:3023884

Fibrosarcoma of the eyelid in two sibling Czech wolfdogs

PubMed Central

Nordio, Laura; Fattori, Sabina; Giudice, Chiara

2017-01-01

Most canine tumors of the eyelid are tumors generally encountered in the skin. They are most commonly of epithelial origin and benign. In this report, we describe the cases of two sibling Czech wolfdogs presented, one year apart, with a subcutaneous mass involving the left eyelid. Both lesions were histologically consistent with a diagnosis of subcutaneous fibrosarcoma. Immunohistochemical analyses of the tumors revealed a mild positivity for vimentin and negativity for GFAP, desmin, αSMA, myoglobin, S100, PNL2 and calponin, excluding all differential diagnosis (i.e. peripheral nerve sheath tumor, melanoma, perivascular sarcoma, myofibroblastic sarcoma, rhabdomyosarcoma). To the best of authors’ knowledge, this is the first report of canine eyelid fibrosarcoma. Since this rare tumor has been observed in two full siblings, we could speculate the existence of some genetic predisposition to sarcoma, however the present data did not allow any definite conclusion on the etiopathogenesis or genetic basis of these tumors. PMID:28616389

Primary fibrosarcoma of the urinary bladder in a cat: follow-up after incomplete surgical excision.

PubMed

Greci, Valentina; Rocchi, Paola M; Sontuoso, Antonio F; Olivero, Daniela; Capasso, Angelo; Raiano, Vera

2017-01-01

An 11-year-old female spayed domestic shorthair cat was presented with haematuria of 2 months' duration followed by pollakiuria and stranguria. A firm, non-painful mass in the urinary bladder was palpated. Abdominal radiographs and ultrasound were suggestive of a urinary neoplasia. During explorative laparotomy, a partial cystectomy and surgical debulking were performed. Histopathology and immunostaining were consistent with a fibrosarcoma. The cat was discharged 10 days after surgery with a residual mass of about 1.8 cm on ultrasound re-examination. The cat was not given adjuvant therapy. The cat was euthanased 8 months after surgery because of tumour invasion of the urinary trigone and subsequent ureter dilation, hydronephrosis and severe azotaemia. Malignant urinary fibrosarcoma in this cat appeared to be only locally invasive. Palliative surgery without adjuvant postoperative chemotherapy in this cat resulted in an 8 month period of good quality of life.

Antitumor effectiveness of different amounts of electrical charge in Ehrlich and fibrosarcoma Sa-37 tumors

PubMed Central

Ciria, HC; Quevedo, MS; Cabrales, LB; Bruzón, RP; Salas, MF; Pena, OG; González, TR; López, DS; Flores, JM

2004-01-01

Background In vivo studies were conducted to quantify the effectiveness of low-level direct electric current for different amounts of electrical charge and the survival rate in fibrosarcoma Sa-37 and Ehrlich tumors, also the effect of direct electric in Ehrlich tumor was evaluate through the measurements of tumor volume and the peritumoral and tumoral findings. Methods BALB/c male mice, 7–8 week old and 20–22 g weight were used. Ehrlich and fibrosarcoma Sa-37 cell lines, growing in BALB/c mice. Solid and subcutaneous Ehrlich and fibrosarcoma Sa-37 tumors, located dorsolaterally in animals, were initiated by the inoculation of 5 × 106 and 1 × 105 viable tumor cells, respectively. For each type of tumor four groups (one control group and three treated groups) consisting of 10 mice randomly divided were formed. When the tumors reached approximately 0.5 cm3, four platinum electrodes were inserted into their bases. The electric charge delivered to the tumors was varied in the range of 5.5 to 110 C/cm3 for a constant time of 45 minutes. An additional experiment was performed in BALB/c male mice bearing Ehrlich tumor to examine from a histolological point of view the effects of direct electric current. A control group and a treated group with 77 C/cm3 (27.0 C in 0.35 cm3) and 10 mA for 45 min were formed. In this experiment when the tumor volumes reached 0.35 cm3, two anodes and two cathodes were inserted into the base perpendicular to the tumor long axis. Results Significant tumor growth delay and survival rate were achieved after electrotherapy and both were dependent on direct electric current intensity, being more marked in fibrosarcoma Sa-37 tumor. Complete regressions for fibrosarcoma Sa-37 and Ehrlich tumors were observed for electrical charges of 80 and 92 C/cm3, respectively. Histopathological and peritumoral findings in Ehrlich tumor revealed in the treated group marked tumor necrosis, vascular congestion, peritumoral neutrophil infiltration, an acute inflammatory response, and a moderate peritumoral monocyte infiltration. The morphologic pattern of necrotic cell mass after direct electric current treatment is the coagulative necrosis. These findings were not observed in any of the untreated tumors. Conclusion The data presented indicate that electrotherapy with low-level DEC is feasible and effective in the treatment of the Ehrlich and fibrosarcoma Sa-37 tumors. Our results demonstrate that the sensitivity of these tumors to direct electric current and survival rates of the mice depended on both the amount of electrical charge and the type of tumor. Also the complete regression of each type of tumor is obtained for a threshold amount of electrical charge. PMID:15566572

Effect of aged garlic extract on immune responses to experimental fibrosarcoma tumor in BALB/c mice.

PubMed

Tabari, M Abouhosseini; Ebrahimpour, S

2014-01-01

Aged garlic extract (AGE) has many biological activities including radical scavenging, antioxidative and immunomodulative effects. In this research work, the antitumor and immunomodulatory effects of AGE against fibrosarcoma implanted tumor were studied. WEHI-164 fibrosarcoma cells were implanted subcutaneously on day 0 into the right flank of 40 BALB/c mice at age of 8 weeks. Mice were randomly categorized in two separate groups: First received AGE (100 mg/kg, IP), second group as the control group received phosphate buffered saline. Treatments were carried out 3 times/week. Tumor growth was measured and morbidity was recorded. Subpopulations of CD4+/CD8+ T cells were determined using flow cytometry. WEHI-164 cell specific cytotoxicity of splenocytes and in vitro production of interferon gamma (IFN-γ) and interleukin-4 cytokines were measured. The mice received AGE had significantly longer survival time compared with the control mice. The inhibitory effect on tumor growth was seen in AGE treated mice. The CD4+/CD8+ ratio and in vitro IFN-γ production of splenocytes were significantly increased in AGE group. WEHI-164 specific cytotoxicity of splenocytes from AGE mice was also significantly increased at 25:1 E: T ratio. Administration of AGE resulted in improved immune responses against experimentally implanted fibrosarcoma tumors in BALB/c mice. AGE showed significant effects on inhibition of tumor growth and longevity of survival times.

Molecular Determinants of Antiestrogen and Drug Sensitivity in Breast Carcinoma Cells

DTIC Science & Technology

1997-08-01

W.S. human HT1080 fibrosarcoma cells (a gift of Pear, personal communication). G.R. Stark), susceptible to ecotropic retrovirus In several...transfection with equal amounts of plasmid pOPRSVIluc (generated by replacing CAT of pORRSVICAT with luc) which expresses luc from R02 promoter, and control...retroviral transduction into (Fig. 1). During transient co-transfection of NIH 3T3 human HT1080 fibrosarcoma or mouse NIH 3T3 cell cells with a laac expressing

Primary intraosseous fibrosarcoma in a cat.

PubMed

Levitt, L; Doige, C E

1989-06-01

A primary intraosseous fibrosarcoma was diagnosed in a 1.5-year-old cat. Clinical signs included nonweight-bearing lameness of the right forelimb and signs of pain on palpation of the right elbow. Radiography of the right elbow revealed a well-circumscribed osteolytic lesion of the olecranon. The right fore-limb was amputated, and histologic examination revealed tumor invasion into local veins and metastasis to the axillary lymph nodes. The cat had no signs of tumor redevelopment or pulmonary metastatic disease one year after amputation.

Central amaurosis induced by an intraocular, posttraumatic fibrosarcoma in a cat.

PubMed

Barrett, P M; Merideth, R E; Alarcon, F L

1995-01-01

A 12-year-old, castrated male, domestic shorthair cat with a previous penetrating trauma to the left globe which progressed to a phthisical eye presented for acute blindness. Ophthalmic examination and electroretinography of the right eye were found to be normal. Following euthanasia, gross and microscopic examinations were completed. A left intraocular, posttraumatic fibrosarcoma with extension to the optic nerve and chiasm and induced right optic nerve fiber degeneration at the optic chiasm with necrosis leading to central amaurosis were diagnosed.

Repair of a facial defect with an interpolation skin flap in a cat.

PubMed

Allen, S W; Miller, M A; Haas, K M

1997-05-01

A 9-year-old domestic shorthair cat was referred for removal of a rostrally located fibrosarcoma on the face, which had previously recurred twice following excision. A wide excision was performed, using a neodymium:yttrium-aluminumgarnet (Nd:YAG) laser, resulting in a facial defect that could not be closed by primary suture. An interpolation skin flap was elevated, using skin from the side of the cat's face, and sutured in place over the defect. Recurrence of the tumor at the medial canthus of the left eye, which was observed 4 months after surgery, was treated by laser excision and cryotherapy. Other recurrences of the fibrosarcoma were not noticed for 2.5 years after referral, at which time the cat was euthanatized for other reasons. Necropsy revealed that the fibrosarcoma had not recurred. In this cat, an interpolation skin flap was useful in repairing a large rostral facial defect. Care should be taken when elevating this flap to preserve the palpebral nerve.

Amplification of the major satellite DNA family (FA-SAT) in a cat fibrosarcoma might be related to chromosomal instability.

PubMed

Santos, Sara; Chaves, Raquel; Adega, Filomena; Bastos, Estela; Guedes-Pinto, Henrique

2006-01-01

Most mammalian chromosomes have satellite DNA sequences located at or near the centromeres, organized in arrays of variable size and higher order structure. The implications of these specific repetitive DNA sequences and their organization for centromere function are still quite cloudy. In contrast to most mammalian species, the domestic cat seems to have the major satellite DNA family (FA-SAT) localized primarily at the telomeres and secondarily at the centromeres of the chromosomes. In the present work, we analyzed chromosome preparations from a fibrosarcoma, in comparison with nontumor cells (epithelial tissue) from the same individual, by in situ hybridization of the FA-SAT cat satellite DNA family. This repetitive sequence was found to be amplified in the cat tumor chromosomes analyzed. The amplification of these satellite DNA sequences in the cat chromosomes with variable number and appearance (marker chromosomes) is discussed and might be related to mitotic instability, which could explain the exhibition of complex patterns of chromosome aberrations detected in the fibrosarcoma analyzed.

Primary fibrosarcoma of the urinary bladder in a cat: follow-up after incomplete surgical excision

PubMed Central

Greci, Valentina; Rocchi, Paola M; Sontuoso, Antonio F; Olivero, Daniela; Capasso, Angelo; Raiano, Vera

2017-01-01

Case summary An 11-year-old female spayed domestic shorthair cat was presented with haematuria of 2 months’ duration followed by pollakiuria and stranguria. A firm, non-painful mass in the urinary bladder was palpated. Abdominal radiographs and ultrasound were suggestive of a urinary neoplasia. During explorative laparotomy, a partial cystectomy and surgical debulking were performed. Histopathology and immunostaining were consistent with a fibrosarcoma. The cat was discharged 10 days after surgery with a residual mass of about 1.8 cm on ultrasound re-examination. The cat was not given adjuvant therapy. The cat was euthanased 8 months after surgery because of tumour invasion of the urinary trigone and subsequent ureter dilation, hydronephrosis and severe azotaemia. Relevance and novel information Malignant urinary fibrosarcoma in this cat appeared to be only locally invasive. Palliative surgery without adjuvant postoperative chemotherapy in this cat resulted in an 8 month period of good quality of life. PMID:28680699

Dataset on FAP-induced emergence of spontaneous metastases and on the preparation of activatable FAP-targeting immunoliposomes to detect the metastases.

PubMed

Tansi, Felista L; Rüger, Ronny; Böhm, Claudia; Kontermann, Roland E; Teichgraeber, Ulf K; Fahr, Alfred; Hilger, Ingrid

2016-12-01

The underlying data demonstrates that fibroblast activation protein (FAP) paves the way for fibrosarcoma cells, which require the proteolysis of the extracellular matrix (ECM) and basement membranes to intravasate from implanted subcutaneous primary tumors into blood vessels, be transported to distant organs where they extravasate from the blood vessels, reattach and proliferate to metastases. The data additionally shows that FAP, when overexpressed on fibrosarcoma cells induces their invasion and formation of spontaneous metastases in multiple organs, particularly after subcutaneous co-implantation of the FAP-expressing and wildtype fibrosarcoma. The raw and processed data presented herein is related to a research article entitled "Potential of activatable FAP-targeting immunoliposomes in intraoperative imaging of spontaneous metastases" (F.L. Tansi, R. Rüger, C. Böhm, R.E. Kontermann, U.K. Teichgraeber, A. Fahr, I. Hilger, 2016) [1]. Furthermore, evidence for the detection of FAP-expressing tumor cells and cells of the tumor stroma by activatable FAP-targeting liposomes is presented in this dataset.

Endocardial fibrosarcoma in a reticulated python (Python reticularis).

PubMed

Gumber, Sanjeev; Nevarez, Javier G; Cho, Doo-Youn

2010-11-01

A female, reticulated python (Python reticularis) of unknown age was presented with a history of lethargy, weakness, and distended coelom. Physical examination revealed severe dystocia and stomatitis. The reticulated python was euthanized due to a poor clinical prognosis. Postmortem examination revealed marked distention of the reproductive tract with 26 eggs (10-12 cm in diameter), pericardial effusion, and a slightly firm, pale tan mass (3-4 cm in diameter) adhered to the endocardium at the base of aorta. Based on histopathologic and transmission electron microscopic findings, the diagnosis of endocardial fibrosarcoma was made.

Phase 1/2 Study of LOXO-195 in Patients With Previously Treated NTRK Fusion Cancers

ClinicalTrials.gov

2018-05-30

Carcinoma, Non-Small-Cell Lung; Thyroid Neoplasms; Sarcoma; Colorectal Neoplasms; Salivary Gland Neoplasms; Biliary Tract Neoplasms; Brain Neoplasm, Primary; Melanoma; Glioblastoma; Bile Duct Neoplasms; Astrocytoma; Head and Neck Squamous Cell Carcinoma; Pontine Glioma; Pancreatic Neoplasms; Ovarian Neoplasms; Carcinoma, Renal Cell; Cholangiocarcinoma; Skin Carcinoma; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Intestinal Neoplasms; Thyroid Cancer; GIST; Malignant Peripheral Nerve Sheath Tumors; Breast Secretory Carcinoma; Uterine Neoplasms; Fibrosarcoma; Infantile Fibrosarcoma; Congenital Mesoblastic Nephroma; Central Nervous System Neoplasms

Chromosome rearrangements in canine fibrosarcomas.

PubMed

Sargan, D R; Milne, B S; Hernandez, J Aguirre; O'Brien, P C M; Ferguson-Smith, M A; Hoather, T; Dobson, J M

2005-01-01

We have previously reported the use of six- and seven-color paint sets in the analysis of canine soft tissue sarcomas. Here we combine this technique with flow sorting of translocation chromosomes, reverse painting, and polymerase chain reaction (PCR) analysis of the gene content of the reverse paint in order to provide a more detailed analysis of cytogenetic abnormalities in canine tumors. We examine two fibrosarcomas, both from female Labrador retrievers, and show abnormalities in chromosomes 11 and 30 in both cases. Evidence of involvement of TGFBR1 is presented for one tumor.

The nature of immunity to Snyder-Theilen fibrosarcoma virus induced tumors in cats.

PubMed

Johnson, L; Pedersen, N C; Theilen, G H

1985-07-01

Snyder-Theilen fibrosarcoma virus (ST-FeSV) induced tumors evoked a vigorous immune response in adolescent cats. The response was characterized histologically by a lymphoid and histiocytic cell infiltrate beginning around the 9th day post inoculation. Hyperemia edema, hemorrhage, and necrosis of the tumors occurred shortly thereafter. Gross regression of the tumors commenced around the 15th day. Viable fibrosarcoma cells could be recovered as almost pure cultures from tumors biopsied on the 9th day. Biopsies taken between days 9 and 15 contained progressively fewer tumor cells and increasing numbers of lymphoid cells, histiocytes, giant cells, and normal fibroblasts. Tumor cells in such mixed cultures did not replicate as fast as normal and died out within 7 to 14 days. Viable tumor cells were not recovered from biopsies taken after day 15. Fibrosarcoma regression was associated with the appearance of tumor cell specific cytotoxic lymphocytes and antibodies in the blood. Cell mediated immunity, as determined by a chromium release assay, consisted of both antibody dependent and independent mechanisms. Fluorescent and complement dependent cytolytic antibodies were detected in the blood at the same time as cytotoxic lymphocytes, but persisted after regression. In a preliminary experiment, serum from tumor regressor cats was injected into susceptible kittens, and the kittens were then challenged with ST-FeSV transformed fibroblasts or whole FeSV. Immune serum did not prevent the appearance of initial growth of tumors, but did slow their subsequent growth and increased the rate of regression. Immune serum had a much more dramatic inhibitory effect on the accompanying retrovirus infection.

Feline vaccine-associated fibrosarcoma: morphologic distinctions.

PubMed

Couto, S S; Griffey, S M; Duarte, P C; Madewell, B R

2002-01-01

Forty-four primary feline vaccine-associated fibrosarcomas and 16 recurrences were examined histologically for detailed morphologic characterization with emphasis on tumor grade, presence of neoplastic multinucleated giant cells, presence and proportion of T and B lymphocytes within the tumor, and thin and intermediate filament contents of neoplastic and stromal cells. The microvascularity and proliferation rates of central and peripheral areas of the tumors were also quantified by computerized image analysis. For primary fibrosarcomas, 11 of 44 (25%) were grade I, 21 of 44 (47.7%) were grade II, and 12 of 44 (27.3%) were grade III. The recurrences followed a similar pattern: 4 of 16 (25%) were grade I, 8 of 16 (50%) were grade II, and 4 of 16 (25%) were grade III. A positive correlation was found between the presence of neoplastic multinucleated giant cells and tumor grade. These cells were present in 9 of 12 (75%) of grade III and none of the grade I tumors. Prominent peritumoral lymphoid aggregates or follicles were present in 59% of the tumors, and many contained high proportions of T lymphocytes, varying from 19 to 87%. All fibrosarcomas were immunoreactive for vimentin and 28 of 44 (64%) were reactive for alpha-smooth muscle actin. The actin-positive cells were either part of the tumor or formed a capsule around tumor nodules. The peripheral vascularity was significantly higher than the central vascular density but no difference was found in tumor cell proliferation rates between the two areas. Centrally located, fluid-filled micro- or macrocavitations were frequently observed in the large vaccine sarcomas and probably formed secondary to rapid tumor growth and central necrosis.

Radical lateral body-wall resection for fibrosarcoma with reconstruction using polypropylene mesh and a caudal superficial epigastric axial pattern flap: a prospective clinical study of the technique and results in 6 cats.

PubMed

Lidbetter, David A; Williams, Fred A; Krahwinkel, D J; Adams, William H

2002-01-01

To describe and evaluate a technique for radical resection of the lateral body wall for treatment of fibrosarcoma with reconstruction using polypropylene mesh and a caudal superficial epigastric axial pattern flap in cats. Prospective, clinical study. Six client-owned cats with fibrosarcoma. Six cats with histologically confirmed fibrosarcoma of the lateral body wall were staged using radiography and/or computer tomography scanning. Preoperative radiotherapy was used in 3 cats. All cats had the lateral abdominal wall resected and reconstructed with polypropylene mesh. A caudal superficial epigastric flap was mobilized and rotated to close the skin deficit. The animals were evaluated after surgery for wound complications, tumor recurrence, and metastasis. Outcome was assessed by patient examination and client consultation. Minor dehiscence of the skin flaps occurred in 2 cats, and 1 other cat was successfully resuscitated from respiratory and cardiac arrest after surgery. All tissue specimens were tumor-free at the surgical margins. Follow-up times ranged from 12 to 21 months, with a mean time of 17.2 months. None of the cats had evidence of local tumor recurrence or metastasis; outcome was judged good to excellent in all cats. Radical lateral body-wall resection and reconstruction is an effective technique for achieving local tumor control with acceptable patient morbidity. Further studies are needed to assess whether the technique will result in improved tumor-free intervals and survival times. Copyright 2002 by The American College of Veterinary Surgeons

Derivation of feline vaccine-associated fibrosarcoma cell line and its growth on chick embryo chorioallantoic membrane - a new in vivo model for veterinary oncological studies.

PubMed

Zabielska, K; Lechowski, R; Król, M; Pawłowski, K M; Motyl, T; Dolka, I; Zbikowski, A

2012-12-01

Feline vaccine associated fibrosarcomas are the second most common skin tumor in cats. Methods of treatment are: surgery, chemotherapy and radiotherapy. Nevertheless, the usage of cytostatics in feline vaccine associated sarcoma therapy is limited due to their adverse side effects, high toxicity and low biodistribution after i.v. injection. Therefore, much research on new therapeutic drugs is being conducted. In human medicine, the chick embryo chorioallantoic membrane (CAM) model is used as a cheap and easy to perform assay to assess new drug effectiveness in cancer treatment. Various human cell lines have different tumors growth on CAM. In veterinary medicine such model has not been described yet. In the present article derivation of feline vaccine associated fibrosarcoma cell line and its growth on CAM is described. The cell line and the tumor grown were confirmed by histopathological and immunohistochemical examination. As far as we believe, this is the first attempt to create such model, which may be used for further in vivo studies in veterinary oncology.

Neoadjuvant gene delivery of feline granulocyte-macrophage colony-stimulating factor using magnetofection for the treatment of feline fibrosarcomas: a phase I trial.

PubMed

Hüttinger, Cornelia; Hirschberger, Johannes; Jahnke, Anika; Köstlin, Roberto; Brill, Thomas; Plank, Christian; Küchenhoff, Helmut; Krieger, Stefan; Schillinger, Ulrike

2008-06-01

Despite aggressive pre- or postoperative treatment, feline fibrosarcomas have high recurrence rates. Immunostimulatory gene therapy is a promising approach in veterinary oncology. This phase I dose-escalation study was performed to determine toxicity and feasibility of gene therapy with feline granulocyte-macrophage colony-stimulating factor (feGM-CSF) in cats with fibrosarcomas. Twenty cats were treated with plasmid coding for feGM-CSF attached to magnetic nanoparticles in doses of 50, 250, 750 and 1250 microg. Two preoperative intratumoral injections followed by magnetofection were given. Four control cats received only surgical treatment. Adverse events were recorded and correlated according to the veterinary co-operative oncology group toxicity scale. An enzyme-linked immunosorbent assay was performed to detect plasma feGM-CSF concentrations. No significant treatment related toxicity was observed. Preliminary recurrence results were encouraging as, on day 360, ten of 20 treated cats were recurrence-free. In conclusion, 1250 microg of feGM-CSF plasmid DNA applied by magnetofection is safe and feasible for phase II testing.

Gliosarcoma developing from an irradiated ependymoma.

PubMed

Kepes, J J; Bastian, F O; Weber, E D

1996-11-01

A 17-year-old girl was operated for a cystic mass located deep within the left parieto-occipital white matter. Histologically the tumor was an ependymoma with a vascular stroma. In spite of irradiation the tumor recurred locally twice, 1 and 2 years respectively after the original operation. The ependymoma portion of the tumor remained unchanged, but the stroma showed increased vascular hyperplasia at the time of the second operation and transformation into a fibrosarcoma in the third operative specimen. Proliferating cell markers (MIB-1) were positive only in the ependymoma cell nuclei in the first two specimens, but were also extensively present in the nuclei of the fibrosarcoma in the third specimen. In the latter, the fibrosarcoma portion greatly overwhelmed the residual ependymoma islands, but remained sharply delineated from them. This is the first observed case of a gliosarcoma originating from an ependymoma. The histological pattern of this mixed tumor clearly indicates that the source of the sarcomatous portions was the neoplastically transformed fibrovascular stroma of the original tumor, rather than "desmoplastic" alterations of the neoplastic ependymal cells themselves.

Apoptosis of mouse MS-2 fibrosarcoma cells induced by photodynamic therapy with Zn (II)-phthalocyanine.

PubMed

Zhou, C; Shunji, C; Jinsheng, D; Junlin, L; Jori, G; Milanesi, C

1996-05-01

The destructive process of mouse MS-2 fibrosarcoma induced by photodynamic therapy (PDT) with liposome-administered Zn(II)-phthalocyanine (ZnPc) was studied by electron microscopy. Pronounced ultrastructural changes characteristic of apoptosis were observed for several tumour cells, including early occurrence of condensation and margination of chromatin, disappearance of nuclear pores, karyopyknosis, karyorrhexis, protuberance formation at the cell surface and cell fragmentation. The findings indicate that apoptosis was involved in the process of tumour cell death induced by ZnPc-PDT. The detailed mechanism and pathways controlling this phenomenon need to be elucidated further.

Feline vaccine-associated fibrosarcoma induced by aluminium compound in two cats: short communication.

PubMed

Deim, Zoltán; Palmai, Nimród; Cserni, Gábor

2008-03-01

Two cases of feline vaccine-associated fibrosarcoma (FVAF) are reported. The excised tumours were both characterised as well circumscribed, subcutaneous, firm and white with central necrosis. Histopathologically, they consisted of well-differentiated and variably sized and shaped anaplastic cells, characterised by marked nuclear and cellular pleomorphism including giant cells. The mitotic activity was low. Aluminium was demonstrated in the central necrosis and giant cells. Neoplastic cells were positive for vimentin and negative for desmin and cytokeratin. The presence of feline sarcoma virus and feline immunodeficiency virus could not be detected by PCR in either case.

Molecular Toxicology of Chromatin: The Role of Poly(ADP-Ribose) in Gene Control.

DTIC Science & Technology

1985-02-01

04 4 0V 0 r4. $) 4 0n U) Ln 𔃺 V W 0 Ř (u %D -T -a Ai j4 W0 .. 04 04 0 04rd 412% I cb 01 41 410 41 .j A . . to 2.4 Ř -A 411 0 2 0 -r 0. 04 0A CAt e4...reported previously (1). The selection procedures used for NNSF * were compared with fibrosarcoma . Ieionmyosarcoui and synovial sarcoma cells. V...tumor incidence of human fibrosarcoma , lelomyosarcoma and synovial sarcoma cells in nude mice was identical with that of UV-transformed human

The use of a latissimus dorsi muscle flap for scapular reconstruction in a cat following fibrosarcoma excision.

PubMed

Canapp, S O; Mann, F A; Henry, C J; Lattimer, J C

2001-01-01

A latissimus dorsi muscle flap was used to reconstruct a proximal scapular defect in a cat after excision of a fibrosarcoma that had recurred after eight surgeries, radiation therapy, and chemotherapy. To obtain appropriate surgical margins, infraspinatus and supraspinatus myectomy and scapular spinous ostectomy were performed. The latissimus dorsi muscle flap was rotated into the defect and anchored to four holes placed in the cranial border of the scapula. The cat showed no lameness at 6, 21, 42, and 147 days after surgery. The latissimus dorsi muscle flap was successful for proximal scapular reconstruction in this cat.

Multicentric Fibrosarcoma in a Cat and a Review of the Literature

PubMed Central

Harasen, G. L. G.

1984-01-01

A case of multicentric fibrosarcoma in a ten month old domestic short-haired cat is presented and discussed. Tumor tissue was found to involve the right distal forepaw, right shoulder area and a popliteal lymph node. This anaplastic neoplasm was concentrated primarily in subcutaneous tissues but also extended to muscle, bone and lung. The cat was found to be positive for feline leukemia virus by the ELISA test. Based on these findings, it is likely that the lesions in this case result from an interaction between the feline leukemia virus and feline sarcoma virus. ImagesFigures 1 and 2.Figure 3.Figure 4. PMID:17422403

Ameloblastic fibrosarcoma of the upper jaw: Report of a rare case with long-term follow-up

PubMed Central

Khalili, Maryam; Shakib, Pouyan Amini

2013-01-01

Ameloblastic fibrosarcoma (AFS) is a rare malignant mixed odontogenic tumor which is usually considered as the malignant counterpart of ameloblastic fibroma. Only mesenchymal component represents sarcomatous alterations and ameloblast-like epithelial nest remains bland in AFS. Here, we report a case of AFS in a 26-year-old man in the maxilla, which was regarded as an uncommon location for this tumor. After 2 years follow up, no evidence of recurrence was noted. We also emphasize on comprehensive clinical, radiographic, and histopathologic evaluation of such patients rather than immunohistochemical staining to make an accurate diagnosis. PMID:23878574

Observation, Radiation Therapy, Combination Chemotherapy, and/or Surgery in Treating Young Patients With Soft Tissue Sarcoma

ClinicalTrials.gov

2017-09-07

Adult Alveolar Soft-part Sarcoma; Adult Angiosarcoma; Adult Epithelioid Sarcoma; Adult Extraskeletal Chondrosarcoma; Adult Extraskeletal Osteosarcoma; Adult Fibrosarcoma; Adult Leiomyosarcoma; Adult Liposarcoma; Adult Malignant Fibrous Histiocytoma; Adult Malignant Hemangiopericytoma; Adult Malignant Mesenchymoma; Adult Neurofibrosarcoma; Adult Synovial Sarcoma; Childhood Alveolar Soft-part Sarcoma; Childhood Angiosarcoma; Childhood Epithelioid Sarcoma; Childhood Fibrosarcoma; Childhood Leiomyosarcoma; Childhood Liposarcoma; Childhood Malignant Mesenchymoma; Childhood Neurofibrosarcoma; Childhood Synovial Sarcoma; Dermatofibrosarcoma Protuberans; Metastatic Childhood Soft Tissue Sarcoma; Nonmetastatic Childhood Soft Tissue Sarcoma; Stage I Adult Soft Tissue Sarcoma; Stage II Adult Soft Tissue Sarcoma; Stage III Adult Soft Tissue Sarcoma; Stage IV Adult Soft Tissue Sarcoma

CVMP advice on injection-site fibrosarcomas in cats.

PubMed

2003-03-29

In response to increasing concern, the Committee for Veterinary Medicinal Products (CVMP) has produced this advisory notice for veterinary surgeons on the development in cats of fibrosarcomas at sites of administration of veterinary medicinal products. The advice relates principally, but not exclusively, to the subcutaneous injection of vaccines. The issue is of relevance only to cats and no extrapolation should be made to other species or to man. At the current state of knowledge, it is not possible to provide specific advice on the risk that any product, or any type of product, might represent in terms of inducing a fibrosarcoma at the site of administration. However, following the precautionary principle, the CVMP considers that information on this issue should be made available to veterinary surgeons in order that they can have an informed discussion with owners of the benefits and risks of therapeutic interventions in cats, particularly in relation to vaccination and re-vaccination. The CVMP wishes to emphasise that modern vaccines continue to represent the only safe and effective means of protecting cats against serious infectious diseases and this should be taken fully into account in any discussion between veterinary surgeons and owners of cats.

Generation of fibrosarcomas in vivo by a retrovirus that expresses the normal B chain of platelet-derived growth factor and mimics the alternative splice pattern of the v-sis oncogene

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pech, M.; Gazit, A.; Arnstein, P.

1989-04-01

A retrovirus containing the entire human platelet-derived growth factor B-chain (PDGF-B) gene was constructed in order to investigate the in vivo biological activity of its encoded growth factor. When this virus was introduced into newborn mice, it reproducibly generated fibrosarcomas at the site of inoculation. Proviruses in each fibrosarcoma analyzed had lost 149 nucleotides downstream of the PDGF-B coding region. This deletion originated from an alternative or aberrant splice event that occurred within exon 7 of the PDGF-B gene and mimicked the v-sis oncogene. Thus, deletion of this region may be necessary for efficient retrovirus replication or for more potentmore » transforming function. Evidence that the normal growth factor coding sequence was unaltered derived from RNase protection studies and immunoprecipitation analysis. Tumors were generally polyclonal but demonstrated clonal subpopulations. Moreover, tumor-derived cell lines became monoclonal within a few tissue culture passages and rapidly formed tumors in vivo. These findings argue that overexpression of the normal human PDGF-B gene product under retrovirus control can induce the fully malignant phenotype.« less

A delayed presentation of ameloblastic fibrosarcoma in an African patient.

PubMed

Chauke, Nkhensani Yvonne; Sofianos, Chrysis; Liakos, Dimitri; Ndobe, Elias

2017-08-01

A 24-year-old womanpresented with ameloblastic fibrosarcoma arising from ameloblastic fibroma. The delayed presentation accounted for the extensive destruction of the mandible and complete occlusion of her oral cavity. This resulted in an inability to eat and maintain oral hygiene. A multidisciplinary team management approach involved nutritional optimisation, segmental mandibulectomy, reconstruction with a reconstructive plate and a free anterolateral thigh flap to line the the floor of mouth. Functional and aesthetic outcome was acceptable, and the patient is planned for secondary free fibular flap bony reconstruction. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Novel p53 tumour suppressor mutations in cases of spindle cell sarcoma, pleomorphic sarcoma and fibrosarcoma in cats.

PubMed

Mayr, B; Reifinger, M; Alton, K; Schaffner, G

1998-06-01

Twenty feline neoplasms were sequenced in the region from exons 5 to 8 for the presence of tumour suppressor gene p53 mutations. In a spindle cell sarcoma of the bladder, a missense mutation (codon 164 AAG-->GAG, lysine-->glutamic acid) in exon 5 was detected. In a pleomorphic sarcoma, a 23 bp deletion involving the splicing junction between intron 5 and exon 6 was observed. In a fibrosarcoma, a 6 bp deletion of p53 covering 2 bp of exon 7 and 4 bp of intron 7, including the splicing junction, was found. The study demonstrates three new p53 mutations in different types of sarcomas in cats.

Sinonasal fibrosarcoma: a case report.

PubMed

Plaza, G; Ferrando, J; Pinedo, F

2006-07-01

Sinonasal fibrosarcoma (SFS) is an infrequent malignant neoplasm. It usually presents as other sarcomas in this region, with nasal obstruction and epistaxis. The final diagnosis is based on the histopathology and immunohistochemistry. We report the case of a 58-year-old man with an 8-month history of left proptosis, recurrent epistaxis and nasal obstruction. Nasal endoscopy confirmed a left nasal neoplasia. CT and MRI showed the extension of the neoplasia, occupying the left nasal fossa and ethmoid sinuses, and eroding the medial wall of the orbit. Complete removal was achieved through endoscopic sinus surgery, preserving the orbit. SFS was found on histopathologic examination. After 4 years of follow-up, nasal endoscopy, CT and MRI imaging show no sign of recurrence.

Determination of the Chronic Mammalian Toxicological Effects of RDX. Twenty-Four Month Chronic Toxicity/Carcinogenicity Study of Hexahydro-1,3,5-Trinitro-1,3,5-Triazine (RDX) in the B6C3F1 Hybrid Mouse. Phase 4, Volume 3, Appendix 11: Final Pathology Report

DTIC Science & Technology

1984-04-01

bladder 1 muscle, s k e l e t a l 5 bone marrow smear --- 3 nasal t u rb ina tes *ti ~ s u e masses ,- and any o the r t i ssues w i t h...Lymphoma, lymphocytic type .__ - __ __ ___ .____. . _ - --- Fibrosarcoma , me ta s t a t i c - __ .._._- _ __._ - - .- Granulosa-cell Carcinoma... Fibrosarcoma , m e t a s t a t i c . -- RENAL LYMPH NODE -- E ’ L - --.I- t Malignant Lymphoma, mixed type Malignant

Pardaxin, a Fish Antimicrobial Peptide, Exhibits Antitumor Activity toward Murine Fibrosarcoma in Vitro and in Vivo

PubMed Central

Wu, Shu-Ping; Huang, Tsui-Chin; Lin, Ching-Chun; Hui, Cho-Fat; Lin, Cheng-Hui; Chen, Jyh-Yih

2012-01-01

The antitumor activity of pardaxin, a fish antimicrobial peptide, has not been previously examined in in vitro and in vivo systems for treating murine fibrosarcoma. In this study, the antitumor activity of synthetic pardaxin was tested using murine MN-11 tumor cells as the study model. We show that pardaxin inhibits the proliferation of MN-11 cells and reduces colony formation in a soft agar assay. Transmission electron microscopy (TEM) showed that pardaxin altered the membrane structure similar to what a lytic peptide does, and also produced apoptotic features, such as hollow mitochondria, nuclear condensation, and disrupted cell membranes. A qRT-PCR and ELISA showed that pardaxin induced apoptosis, activated caspase-7 and interleukin (IL)-7r, and downregulated caspase-9, ATF 3, SOCS3, STAT3, cathelicidin, p65, and interferon (IFN)-γ suggesting that pardaxin induces apoptosis through the death receptor/nuclear factor (NF)-κB signaling pathway after 14 days of treatment in tumor-bearing mice. An antitumor effect was observed when pardaxin (25 mg/kg; 0.5 mg/day) was used to treat mice for 14 days, which caused significant inhibition of MN-11 cell growth in mice. Overall, these results indicate that pardaxin has the potential to be a novel therapeutic agent to treat fibrosarcomas. PMID:23015777

INTERFERON α ACTIVATES NF-κ B IN JAK1-DEFICIENT CELLS THROUGH A TYK2-DEPENDENT PATHWAY

PubMed Central

Yang, Chuan He; Murti, Aruna; Valentine, William J.; Du, Ziyun; Pfeffer, Lawrence M.

2005-01-01

In addition to activating members of the STAT transcription factor family, IFN α/β activates the NF-κ B transcription factor. To determine the role of the JAK-STAT pathway in NF-κ B activation by IFN, we examined NF-κ B activation in JAK1-deficient mutant human fibrosarcoma cells. In wild-type fibrosarcoma cells (2fTGH) IFN activates STAT1, STAT2 and STAT3, as well as NF-κB complexes comprised of p50 and p65. In contrast, in JAK1-deficient cells IFN induces NF-κB activation and NF-κB dependent gene transcription, but does not activate these STAT proteins and has no effect on STAT-dependent gene transcription. Expression of a catalytically-inactive TYK2 tyrosine kinase in JAK1-deficient cells, as well as in the highly IFN-sensitive Daudi lymphoblastoid cell line, abrogates NF-κB activation by IFN. Moreover, IFN does not promote NF-κB activation in TYK2-deficient mutant fibrosarcoma cells. Our results demonstrate a dichotomy between the classical JAK-STAT pathway and the NF-κB signaling pathway. In the IFN signaling pathway leading to STAT activation both JAK1 and TYK2 are essential, while NF-κB activation requires only TYK2. PMID:15883164

Biological behavior of tumors and associated retroviremia in cats inoculated with Snyder-Theilen fibrosarcoma virus and the phenomenon of tumor recurrence after primary regression.

PubMed Central

Pedersen, N C; Johnson, L; Theilen, G H

1984-01-01

The fate of tumors and associated retroviremia was studied in 111 cats infected with the Snyder-Theilen strain of feline sarcoma virus (FeSV). Tumors appeared at the site of inoculation within 7 to 10 days. A retroviremia, due mainly to the associated feline leukemia virus helper virus (FeLV-helper), developed at the same time as tumors. Of the cats, 44 developed progressively growing tumors and therefore had to be killed, and 67 developed tumors that regressed. There was a strong correlation between the persistence of the accompanying retroviremia and the growth of the tumors. The 44 cats with progressively growing fibrosarcomas remained retroviremic until death. Conversely, 53 of the 67 cats with solitary, regressing tumors were only transiently retroviremic. Tumor regression in these cats paralleled the disappearance of retrovirus from the blood. The fate of tumors and retroviremia was not always the same, however. Twelve cats remained persistently retroviremic after all signs of gross tumors disappeared. Two other kittens became nonviremic within 20 days after inoculation, yet tumors continued to grow and even metastasize for another 3 to 5 weeks before regressing. Fibrosarcomas recurred 3 weeks to 8 months later in 8 of 12 persistently retroviremic cats with regressed tumors. Although the blood and bone marrow from these cats contained predominantly FeLV-helper, tumor cells yielded both FeSV and FeLV-helper. Of 53 animals, 3 developed recurrent fibrosarcomas 5 weeks to 8 months after all signs of tumors and retroviremia had disappeared. Cells cultured from these tumors appeared initially like normal fibroblasts and were virus nonproducers. After one to three passages in culture, however, cells became malignantly transformed and replicated both FeSV and FeLV-helper. Cultures of the bone marrow from these and other nonviremic cats with regressed tumors yielded only FeLV-helper. PMID:6319286

Dedifferentiated liposarcoma of the spermatic cord: a series of 42 cases.

PubMed

Kryvenko, Oleksandr N; Rosenberg, Andrew E; Jorda, Merce; Epstein, Jonathan I

2015-09-01

Dedifferentiated liposarcoma (DDL) of the spermatic cord is rare, with limited data regarding morphology and prognosis. We analyzed the morphologic spectrum of DDL of the spermatic cord and its clinical significance in 42 patients from 1990 to 2014. The median age of the patients was 70.5 years (range: 43 to 90 y). The median tumor size was 10.9 cm (range: 3 to 30 cm). Six cases were low-grade DDL, 28 were high-grade DDL, and in 8 cases both coexisted. Five cases had osteosarcoma, and 2 had leiomyosarcoma differentiation. Low-grade DDL had a fibrosarcoma-like (n=11), myxofibrosarcoma-like (n=2), and fibrosarcoma and inflammatory-like (n=1) pattern. High-grade DDL had a fibrosarcoma-like (n=22), undifferentiated pleomorphic sarcoma-like (n=7), myxofibrosarcoma and undifferentiated pleomorphic sarcoma-like (n=4), fibrosarcoma and undifferentiated pleomorphic sarcoma-like (n=2), and myxofibrosarcoma-like (n=1) pattern. Resection margins were positive in 22, negative in 13, and unknown in 7 cases. MDM2 was positive in 24/24 cases. Two patients received neoadjuvant radiotherapy (1 with chemotherapy). Patients received postoperative radiation (n=13), reexcision (n=5) with radiation (n=3), chemotherapy (n=2), chemotherapy and radiation (n=1), no therapy (n=11), and unknown (n=6). Follow-up information was available in 31 patients (mean: 54.2 mo; median: 38.5 mo; range: 2 to 180 mo). Seven patients developed local recurrence. Two patients had systemic metastases and succumbed to disease. Recurrence developed at an average of 40.9 months (median: 24 mo; range: 12 to 100 mo) after resection. Average follow-up in patients without recurrence was 45.2 months (median: 25 mo; range: 2 to 180 mo) (P=0.87). Margin status, size, and grade did not correlate with recurrence (P>0.05). Thus, DDL of the spermatic cord includes a spectrum of morphologic patterns. Complete excision is difficult at first attempt. Local recurrence is common, and relatively few patients develop systemic disease.

Mitochondrial dynamics and respiration within cells with increased open pore cytoskeletal meshes

PubMed Central

Jang, David H.; Seeger, Sarah C.; Grady, Martha E.; Shofer, Frances S.

2017-01-01

ABSTRACT The cytoskeletal architecture directly affects the morphology, motility, and tensional homeostasis of the cell. In addition, the cytoskeleton is important for mitosis, intracellular traffic, organelle motility, and even cellular respiration. The organelle responsible for a majority of the energy conversion for the cell, the mitochondrion, has a dependence on the cytoskeleton for mobility and function. In previous studies, we established that cytoskeletal inhibitors altered the movement of the mitochondria, their morphology, and their respiration in human dermal fibroblasts. Here, we use this protocol to investigate applicability of power law diffusion to describe mitochondrial locomotion, assessment of rates of fission and fusion in healthy and diseased cells, and differences in mitochondria locomotion in more open networks either in response to cytoskeletal destabilizers or by cell line. We found that mitochondria within fibrosarcoma cells and within fibroblast cells treated with an actin-destabilizing toxin resulted in increased net travel, increased average velocity, and increased diffusion of mitochondria when compared to control fibroblasts. Although the mitochondria within the fibrosarcoma travel further than mitochondria within their healthy counterparts, fibroblasts, the dependence on mitochondria for respiration is much lower with higher rates ofhydrogen peroxide production and was confirmed using the OROBOROS O2K. We also found that rates of fission and fusion of the mitochondria equilibrate despite significant alteration of the cytoskeleton. Rates ranged from 15% to 25%, where the highest rates were observed within the fibrosarcoma cell line. This result is interesting because the fibrosarcoma cell line does not have increased respiration metrics including when compared to fibroblast. Mitochondria travel further, faster, and have an increase in percent mitochondria splitting or joining while not dependent on the mitochondria for a majority of its energy production. This study illustrates the complex interaction between mitochondrial movement and respiration through the disruption of the cytoskeleton. PMID:29109116

Atypical fibrosarcomas derived from cutaneous ganglion cell-like cells in 2 domestic Djungarian hamsters (Phodopus sungorus).

PubMed

Kondo, Hirotaka; Onuma, Mamoru; Shibuya, Hisashi; Sato, Tsuneo; Abbott, Jeffrey R

2011-07-01

Androgen-dependent atypical fibromas are benign tumors derived from ganglion-cell-like cells that are particular to Djungarian hamsters (Phodopus sungorus). Masses excised from 2 hamsters were composed of pleomorphic ganglion cell-like cells supported by small to moderate amounts of collagenous matrix. Intracytoplasmic fibrils were present in silver-stained sections, and immunohistochemistry showed that the cells expressed vimentin, androgen receptor, and, in one case, estrogen receptor α. In contrast to previously reported atypical fibromas, these tumors had features of anaplasia and were locally invasive. We diagnosed the tumors as atypical fibrosarcomas and consider them an unusual malignant counterpart of atypical fibroma. Copyright 2011 by the American Association for Laboratory Animal Science

Combined doxorubicin and cyclophosphamide chemotherapy for nonresectable feline fibrosarcoma.

PubMed

Barber, L G; Sørenmo, K U; Cronin, K L; Shofer, F S

2000-01-01

A retrospective evaluation was performed on 12 cats with nonresectable, histopathologically confirmed fibrosarcomas that were treated with doxorubicin and cyclophosphamide chemotherapy. All of the tumors were located in sites potentially used for vaccination. Six cats had a greater than 50% decrease in gross tumor burden. However, the responses were not durable, with a median response duration of 125 days. All cats developed progressive disease. When animals that received other treatments after doxorubicin-based chemotherapy were eliminated from the analysis, median survival time was significantly longer for cats that responded to chemotherapy compared with the median survival time for nonresponders (242 and 83 days, respectively). These findings may serve as a basis for further evaluating the role of chemotherapy in the treatment of vaccine-associated sarcomas.

Long acting propranolol and HSP-70 rich tumor lysate reduce tumor growth and enhance immune response against fibrosarcoma in Balb/c mice.

PubMed

Khalili, Ahmad; Hassan, Zuhair Muhammad; Shahabi, Shahram; Pourfathollah, Ali Akbar; Ostad, Seyed Nasser; Noori, Shokoofe; Mahdavi, Mehdi; Haybar, Habib; Langroudi, Ladan

2013-06-01

Noradrenaline (NA), the principal neurotransmitter released from sympathetic nerve terminals, influences T-cell maturation, not only directly in developing T cells, but also indirectly, by acting on the thymic nonlymphoid cells. In vitro and in vivo studies have demonstrated the anti-proliferative, anti-migratory, anti-angiogenic and cytotoxic properties of propranolol, β-AR blocker, against various cancers. To evaluate the effect of propranolol on efficacy of HSP-70 rich lysate vaccine in immunotherapy of fibrosarcoma. Mouse fibrosarcoma WEHI-164 cells were used to immunize tumor-bearing mice with or without propranolol and HSP-70. Splenocytes proliferation, cytotoxicity activity of the splenocytes, naturally occurring CD4+ CD25high T-reg cells and IFN-γ and IL-4 secretion as well as tumor size, were assessed to describe the anti-tumor immune response. A significant increase in the level of IFN-γ in the mice vaccinated with WEHI-164 cells enriched with HSP-70 and co-treated with propranolol was observed compared to controls. However, HSP enrichment or propranolol treatment alone did not enhance the immune response as measured by the level of IFN-γ. Likewise, a decrease in tumor growth in the test group (p<0.01) and a significant increase in CTL activity (p<0.05) was observed. HSP enriched vaccine shows anti-tumor activity, probably due to the modulation of immune responses.

Suppression of human fibrosarcoma cell growth by transcription factor, Egr-1, involves down-regulation of Bcl-2.

PubMed

Huang, R P; Fan, Y; Peng, A; Zeng, Z L; Reed, J C; Adamson, E D; Boynton, A L

1998-09-11

Previously, we showed that the transcription factor Egr-1 suppressed the proliferation of v-sis transformed NIH3T3 cells and also a number of human tumor cells. Here, we investigate the possible mechanisms responsible for this function. We show that transfected Egr-1 in human fibrosarcoma cells HT1080 leads to down-regulation of Bcl-2. Transient CAT transfection assays reveal that expression of Egr-1 suppresses Bcl-2 promoter activity in a dose-dependent manner. Furthermore, overexpression of Bcl-2 in Egr-1-expressing HT1080 cells enhanced cell proliferation in monolayer culture and increased anchorage-independent growth. Our results suggest that suppression of tumor cell proliferation by Egr-1 may be at least partially mediated through the down-regulation of Bcl-2.

Microchip-associated fibrosarcoma in a cat.

PubMed

Carminato, Antonio; Vascellari, Marta; Marchioro, Wendy; Melchiotti, Erica; Mutinelli, Franco

2011-12-01

A 9-year-old, neutered male cat was presented for a subcutaneous mass on the neck. After surgical removal of the mass, a pet identification microchip was found within the tumour. Histological examination of the mass revealed typical features of the feline postinjection sarcoma. The cat had never received injections at the tumour site; all routine vaccinations were administered in the hindlimbs. Few cases of sarcomas developing at the site of microchip application have been reported in animals, although the contributory role of vaccine administrations has not been ruled out. This is the first report of a microchip-associated fibrosarcoma in a cat. Adherence to American Association of Feline Practitioners vaccination guidelines, avoiding the interscapular area, enabled confirmation of the definitive aetiology of the neoplasia. © 2011 The Authors. Veterinary Dermatology. © 2011 ESVD and ACVD.

Near-infrared optical guided surgery of highly infiltrative fibrosarcomas in cats using an anti-αvß3 integrin molecular probe.

PubMed

Wenk, Christiane H F; Ponce, Frédérique; Guillermet, Stéphanie; Tenaud, Corinne; Boturyn, Didier; Dumy, Pascal; Watrelot-Virieux, Dorothée; Carozzo, Claude; Josserand, Véronique; Coll, Jean-Luc

2013-07-01

We investigated how near-infrared imaging could improve highly infiltrative spontaneous fibrosarcoma surgery in 12 cats in a clinical veterinary phase. We used an RGD-based nanoprobe at different doses and times before surgery and a portable clinical grade imaging system. All tumours were labelled by the tracer and had an overall tumour-to-healthy tissue ratio of 14±1 during surgery. No false negatives were found, and the percentage of tumour cells was linearly correlated with the fluorescence intensity. All cats recovered well and were submitted to long-term follow-up that is currently on-going 1year after the beginning of the study. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Postvaccinal sarcomas in the cat: epidemiology and electron probe microanalytical identification of aluminum

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hendrick, M.J.; Goldschmidt, M.H.; Shofer, F.S.

1992-10-01

An increase in fibrosarcomas in a biopsy population of cats in the Pennsylvania area appears to be related to the increased vaccination of cats following enactment of a mandatory rabies vaccination law. The majority of fibrosarcomas arose in sites routinely used by veterinarians for vaccination, and 42 of 198 tumors were surrounded by lymphocytes and macrophages containing foreign material identical to that previously described in postvaccinal inflammatory injection site reactions. Some of the vaccines used have aluminum-based adjuvants, and macrophages surrounding three tumors contained aluminum oxide identified by electron probe microanalysis and imaged by energy-filtered electron microscopy. Persistence of inflammatorymore » and immunological reactions associated with aluminum may predispose the cat to a derangement of its fibrous connective tissue repair response, leading to neoplasia.« less

Doxorubicin With Upfront Dexrazoxane Plus Olaratumab for the Treatment of Advanced or Metastatic Soft Tissue Sarcoma

ClinicalTrials.gov

2018-02-08

Sarcoma, Soft Tissue; Soft Tissue Sarcoma; Undifferentiated Pleomorphic Sarcoma; Leiomyosarcoma; Liposarcoma; Synovial Sarcoma; Myxofibrosarcoma; Angiosarcoma; Fibrosarcoma; Malignant Peripheral Nerve Sheath Tumor; Epithelioid Sarcoma

Cixutumumab and Doxorubicin Hydrochloride in Treating Patients With Unresectable, Locally Advanced, or Metastatic Soft Tissue Sarcoma

ClinicalTrials.gov

2016-05-16

Adult Angiosarcoma; Adult Desmoplastic Small Round Cell Tumor; Adult Epithelioid Sarcoma; Adult Extraskeletal Myxoid Chondrosarcoma; Adult Extraskeletal Osteosarcoma; Adult Fibrosarcoma; Adult Leiomyosarcoma; Adult Liposarcoma; Adult Malignant Mesenchymoma; Adult Malignant Peripheral Nerve Sheath Tumor; Adult Rhabdomyosarcoma; Adult Synovial Sarcoma; Adult Undifferentiated High Grade Pleomorphic Sarcoma of Bone; Childhood Angiosarcoma; Childhood Desmoplastic Small Round Cell Tumor; Childhood Epithelioid Sarcoma; Childhood Fibrosarcoma; Childhood Leiomyosarcoma; Childhood Liposarcoma; Childhood Malignant Mesenchymoma; Childhood Malignant Peripheral Nerve Sheath Tumor; Childhood Pleomorphic Rhabdomyosarcoma; Childhood Rhabdomyosarcoma With Mixed Embryonal and Alveolar Features; Childhood Synovial Sarcoma; Dermatofibrosarcoma Protuberans; Malignant Adult Hemangiopericytoma; Malignant Childhood Hemangiopericytoma; Metastatic Childhood Soft Tissue Sarcoma; Previously Treated Childhood Rhabdomyosarcoma; Recurrent Adult Soft Tissue Sarcoma; Recurrent Childhood Rhabdomyosarcoma; Recurrent Childhood Soft Tissue Sarcoma; Stage III Adult Soft Tissue Sarcoma; Stage IV Adult Soft Tissue Sarcoma; Untreated Childhood Rhabdomyosarcoma

Specific binding of TES-23 antibody to tumour vascular endothelium in mice, rats and human cancer tissue: a novel drug carrier for cancer targeting therapy

PubMed Central

Tsunoda, S; Ohizumi, I; Matsui, J; Koizumi, K; Wakai, Y; Makimoto, H; Tsutsumi, Y; Utoguchi, N; Taniguchi, K; Saito, H; Harada, N; Ohsugi, Y; Mayumi, T

1999-01-01

The tissue distribution of anti-tumour vascular endothelium monoclonal antibody (TES-23) produced by immunizing with plasma membrane vesicles from isolated rat tumour-derived endothelial cells (TECs) was assessed in various tumour-bearing animals. Radiolabelled TES-23 dramatically accumulated in KMT-17 fibrosarcoma, the source of isolated TECs after intravenous injection. In Meth-A fibrosarcoma, Colon-26 adenocarcinoma in BALB/c mice and HT-1080 human tumour tissue in nude mice, radioactivities of 125I-labelled TES-23 were also up to 50 times higher than those of control antibody with little distribution to normal tissues. The selective recognition of TES-23 to TECs was competitively blocked by preadministration of unlabelled TES-23 in vivo. Furthermore, immunostaining of human tissue sections showed specific binding of TES-23 on endothelium in oesophagus cancers. These results indicate that tumour vascular endothelial cells express common antigen in different tumour types of various animal species. In order to clarify the efficacy of TES-23 as a drug carrier, an immunoconjugate, composed of TES-23 and neocarzinostatin, was tested for its anti-tumour effect in rats bearing KMT-17 fibrosarcomas. The immunoconjugate (TES-23-NCS) caused marked regression of the tumour, accompanied by haemorrhagic necrosis. Thus, from a clinical view, TES-23 would be a novel drug carrier because of its high specificity to tumour vascular endothelium and its application to many types of cancer. © 1999 Cancer Research Campaign PMID:10584876

Radiation Therapy With or Without Combination Chemotherapy or Pazopanib Hydrochloride Before Surgery in Treating Patients With Newly Diagnosed Non-rhabdomyosarcoma Soft Tissue Sarcomas That Can Be Removed by Surgery

ClinicalTrials.gov

2018-06-20

Adult Fibrosarcoma; Alveolar Soft Part Sarcoma; Angiomatoid Fibrous Histiocytoma; Atypical Fibroxanthoma; Clear Cell Sarcoma of Soft Tissue; Epithelioid Malignant Peripheral Nerve Sheath Tumor; Epithelioid Sarcoma; Extraskeletal Myxoid Chondrosarcoma; Extraskeletal Osteosarcoma; Fibrohistiocytic Neoplasm; Glomus Tumor of the Skin; Inflammatory Myofibroblastic Tumor; Intimal Sarcoma; Leiomyosarcoma; Liposarcoma; Low Grade Fibromyxoid Sarcoma; Low Grade Myofibroblastic Sarcoma; Malignant Cutaneous Granular Cell Tumor; Malignant Peripheral Nerve Sheath Tumor; Malignant Triton Tumor; Mesenchymal Chondrosarcoma; Myxofibrosarcoma; Myxoid Chondrosarcoma; Myxoinflammatory Fibroblastic Sarcoma; Nerve Sheath Neoplasm; PEComa; Pericytic Neoplasm; Plexiform Fibrohistiocytic Tumor; Sclerosing Epithelioid Fibrosarcoma; Stage IB Soft Tissue Sarcoma AJCC v7; Stage IIB Soft Tissue Sarcoma AJCC v7; Stage III Soft Tissue Sarcoma AJCC v7; Stage IV Soft Tissue Sarcoma AJCC v7; Synovial Sarcoma; Undifferentiated (Embryonal) Sarcoma; Undifferentiated High Grade Pleomorphic Sarcoma of Bone

Sarcomas of nasal cavity and paranasal sinuses: chondrosarcoma, osteosarcoma and fibrosarcoma.

PubMed

Koka, V; Vericel, R; Lartigau, E; Lusinchi, A; Schwaab, G

1994-11-01

Forty-two patients were treated for sarcoma of the nasal cavity and paranasal sinuses at the Institut Gustave Roussy, Paris, between 1960 and 1993. Twelve patients had chondrosarcoma (CS), 14 had osteosarcoma (OS) and 16 had fibrosarcoma (FS). Ten patients had grade I, six grade II and 26 grade III tumours. All but 10 patients had surgery for the primary tumour. A significantly increased risk of local failure was associated with the male sex (p < 0.01), grade III tumours (p < 0.02) and patients excluded from surgery (p < 0.04). The overall incidence of local and distant failure was 76 and 12 per cent respectively. Overall survival was 28 per cent at three years and 23 per cent at five years. Eight patients (20 per cent) were alive more than 10 years later. The factors significantly influencing survival were sex (p < 0.01), grade (p < 0.05) and local failure (p < 0.01).

Spontaneous generation of germline characteristics in mouse fibrosarcoma cells

NASA Astrophysics Data System (ADS)

Ma, Zhan; Hu, Yao; Jiang, Guoying; Hou, Jun; Liu, Ruilai; Lu, Yuan; Liu, Chunfang

2012-10-01

Germline/embryonic-specific genes have been found to be activated in somatic tumors. In this study, we further showed that cells functioning as germline could be present in mouse fibrosarcoma cells (L929 cell line). Early germline-like cells spontaneously appeared in L929 cells and further differentiated into oocyte-like cells. These germline-like cells can, in turn, develop into blastocyst-like structures in vitro and cause teratocarcinomas in vivo, which is consistent with natural germ cells in function. Generation of germline-like cells from somatic tumors might provide a novel way to understand why somatic cancer cells have strong features of embryonic/germline development. It is thought that the germline traits of tumors are associated with the central characteristics of malignancy, such as immortalization, invasion, migration and immune evasion. Therefore, germline-like cells in tumors might provide potential targets to tumor biology, diagnosis and therapy.

The radiosensitivity of a murine fibrosarcoma as measured by three cell survival assays.

PubMed Central

Rice, L.; Urano, M.; Suit, H. D.

1980-01-01

The radiation sensitivity of a weakly immunogenic spontaneous fibrosarcoma of the C3Hf/Sed mouse (designated FSa-II) was assessed by three in vivo cell survival methods: end-point dilution (TD50) assay, lung colony (LC) assay, and agar diffusion chamber (ADC) assay. The hypoxic fraction of this tumour was also determined by the ADC method. Although there was a good agreement of the cell survival data between the ADC and LC methods, the TD50 method yielded a considerably less steep cell survival curve. Beneficial aspects and limitations of each assay are discussed. In addition, the use of the ADC method for the growth of xenogeneic cell lines and a preliminary experiment with human tumour cells in non-immunosuppressed hosts suggest that this method may be a valuable adjunct for studying the growth and therapeutic responses of human tumour cells. PMID:6932931

Caffeine induces metformin anticancer effect on fibrosarcoma in hamsters.

PubMed

Popović, D J; Lalošević, D; Miljković, D; Popović, K J; Čapo, I; Popović, J K

2018-04-01

We investigated the effect of metformin and caffeine on fibrosarcoma in hamsters. 32 Syrian golden hamsters of both sexes, weighing approximately 100 g, were randomly allocated to 3 experimental and 2 control groups, with a minimum of 6 animals per group. 2 x 106 BHK-21/C13 cells in 1 ml were injected subcutaneously into the animals' back in 4 groups. The first experimental group started peroral treatment with metformin 500 mg/kg daily, the second with caffeine 100 mg/kg daily and the third with a combination of metformin 500 mg/kg and caffeine 100 mg/kg daily, via a gastric probe 3 days before tumor inoculation. After 2 weeks, when the tumors were approximately 2 cm in the control group, all animals were sacrificed. The blood was collected for glucose and other analyses. The tumors were excised and weighed and their diameters were measured. The tumor samples were pathohistologically (HE) and immunohistochemically (Ki-67, CD 31, COX IV, GLUT-1, iNOS) assessed and the main organs toxicologically analyzed, including the control animals that had received metformin and caffeine. Tumor volume was determined using the formula LxS2/2, where L was the longest and S the shortest diameter. Ki-67-positive cells in the tumor samples were quantified. Images were taken and processed by software UTHSCSA Image Tools for Windows Version 3.00. Statistical significances were determined by the Student's t-test. The combination of metformin and caffeine inhibited fibrosarcoma growth in hamsters without toxicity. Administration of metformin with caffeine might be an effective and safe approach in novel nontoxic adjuvant anticancer treatment.

A novel rat fibrosarcoma cell line from transformed bone marrow-derived mesenchymal stem cells with maintained in vitro and in vivo stemness properties

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Meng-Yu; Nestvold, Janne, E-mail: j.m.nestvold@medisin.uio.no; Rekdal, Øystein

Increasing evidence suggests a possible relationship between mesenchymal stem cells (MSCs) and sarcoma. MSCs are hypothesized to be the cells initiating sarcomagenesis, and cancer stem cells (CSCs) sharing features of MSCs have been identified in sarcomas. Here, we report on the characteristics of a bone marrow-derived rat mesenchymal stem cell line that spontaneously transformed in long-term culture. The rat transformed mesenchymal stem cells (rTMSCs) produced soft-tissue fibrosarcomas in immunocompromised mice and immunocompetent rats. In vitro, the rTMSCs displayed increased proliferation capacity compared to the untransformed cell line. The transformed MSCs maintained the mesenchymal phenotype by expression of the stem cellmore » marker CD 90 and the lack of hematopoietic and endothelial markers. Cytogenetic analysis detected trisomy 6 in the rTMSCs. Side population (SP) isolation and tumorsphere cultivation of the transformed cells confirmed the presence of CSCs among the rTMSCs. Importantly, the rTMSCs retained their differentiation capacity towards osteogenic and adipogenic lineages. This transformed MSC-based cell line may be valuable in examining the balance in a mixed cell population between cancer stem cell properties and the ability to differentiate to specific non-transformed cell populations. Moreover, it may also be a useful tool to evaluate the efficacy of novel targeted immunotherapies in vivo. - Highlights: • Spontaneously transformed rat MSCs (rTMSCs) share characteristics with normal MSCs. • rTMSCs possess a side population, enriched with tumorigenic cells. • rTMSCs model fibrosarcoma in vivo.« less

Huaier aqueous extract induces apoptosis of human fibrosarcoma HT1080 cells through the mitochondrial pathway

PubMed Central

CUI, YANG; MENG, HONGMEI; LIU, WEIDONG; WANG, HUAN; LIU, QINGPENG

2015-01-01

In recent years, aqueous extract of Trametes robiniophila Murr. (Huaier), a traditional Chinese medicine, has been frequently used in China for complementary cancer therapy. However, the mechanisms underlying its anticancer effects have yet to be elucidated. The present study aimed to evaluate the ability of Huaier extract to inhibit proliferation, promote apoptosis and suppress mobility in the fibrosarcoma HT1080 cell line in vitro. The cells were treated with gradient doses of Huaier extract at concentrations of 0, 4, 8 or 16 mg/ml for 24, 48 or 72 h. The cell viability and motility were measured in vitro using MTT, invasive, migration and scratch assays. The distribution of the cell cycle and the extent of cellular apoptosis were analyzed by flow cytometry. The apoptotic pathways were detected using a mitochondrial membrane potential transition assay and western blotting. The results revealed that the cellular viability decreased significantly with increasing concentrations of Huaier extract. In addition, cell invasiveness and migration were also suppressed significantly. It was demonstrated that Huaier extract induced G2 cell-cycle arrest and cellular apoptosis in a time- and dose-dependent manner. The decreased mitochondrial membrane potential, the downregulation of B-cell lymphoma 2 and pro-caspase-3, and upregulation of Bcl-2-associated X protein, cleaved caspase-9 and caspase-3 suggested that Huaier extract induced the apoptosis of HT1080 cells through the mitochondrial pathway. The results of the present study indicate that Huaier extract is a potential complementary agent for the treatment of fibrosarcoma. PMID:25789006

Measurement of differences in pO2 in response to perfluorocarbon/carbogen in FSa and NFSa murine fibrosarcomas with low-frequency electron paramagnetic resonance oximetry.

PubMed

Halpern, H J; Yu, C; Peric, M; Barth, E D; Karczmar, G S; River, J N; Grdina, D J; Teicher, B A

1996-05-01

We have used very low-frequency electron paramagnetic resonance (EPR) oximetry to measure the change in oxygen concentration (delta pO2) due to change in breathing atmosphere in FSa and NFSa fibrosarcomas implanted in the legs of C3H mice infused with perfluoro-octylbromine (PFOB). Measurements in each tumor were made before and after the administration of the high-density (47% v/v) perfluorocarbon PFOB, perflubron (Alliance Pharmaceutical Corporation, San Diego, CA). Measurements in each tumor were also made, after the administration of the PFOB, both before (PFOB/air) and after the administration of carbogen (95% O2 + 5% CO2, PFOB/carbogen). Large changes (delta p02) relative to PFOB/air oxygenation were seen with the administration of PFOB/carbogen. No significant difference in oxygen concentration was seen between air-breathing mice with and without PFOB. The mean delta pO2 for FSa tumors was 13 +/- 6 torr, while the mean for NFSa fibrosarcomas was 28 +/- 7 torr. There were such large intertumor differences that the trend toward a smaller change in the more hypoxic FSa tumors was not significant (P = 0.13). This paper describes a novel method of measuring differences in oxygenation in tumor tissues. The results of such measurements indicate large differences in pO2 response to different breathing atmospheres in PFOB-infused tumors of similar histology. The intertumor delta pO2 differences may correlate with differences in radiation response.

Synthesis and evaluation of novel Tc-99m labeled NGR-containing hexapeptides as tumor imaging agents.

PubMed

Kim, Dae-Weung; Kim, Woo Hyoung; Kim, Myoung Hyoun; Kim, Chang Guhn

2015-02-01

Asparagine-glycine-arginine (NGR)-containing peptides targeting aminopeptidase N (APN)/CD13 can be an excellent candidate for targeting ligands in molecular tumor imaging. In this study, we developed two NGR-containing hexapeptides, and evaluated the diagnostic performance of Tc-99m labeled hexapeptides as molecular imaging agents in an HT-1080 fibrosarcoma-bearing murine model. Peptides were synthesized using Fmoc solid-phase peptide synthesis. Radiochemical purity of Tc-99m was evaluated using instant thin-layer chromatography. The uptake of two NGR-containing hexapeptides within HT-1080 cells was evaluated in vitro. In HT-1080 fibrosarcoma tumor-bearing mice, gamma images were acquired. A biodistribution study was performed to calculate percentage of the injected dose per gram of tissue (%ID/g). Two hexapeptides, glutamic acid-cysteine-glycine (ECG)-NGR and NGR-ECG were successfully synthesized. After radiolabeling procedures with Tc-99m, the complexes Tc-99m hexapeptides were prepared in high yield. The uptake of Tc-99m ECG-NGR within the tumor cells had been assured by in vitro studies. The gamma camera imaging in the murine model showed that Tc-99m ECG-NGR was accumulated substantially in the subcutaneously engrafted tumor. However, Tc-99m NGR-ECG was accumulated minimally in the tumor. Two NGR-containing hexapeptides, ECG-NGR and NGR-ECG were developed as molecular imaging agents to target APN/CD13 in HT-1080 fibrosarcoma. Tc-99m ECG-NGR showed a significant uptake in the tumor, and it is a good candidate for tumor imaging. Copyright © 2015 John Wiley & Sons, Ltd.

Primary mesenchymal (nonangiomatous/nonlymphomatous) neoplasms occurring in the canine spleen: anatomic classification, immunohistochemistry, and mitotic activity correlated with patient survival.

PubMed

Spangler, W L; Culbertson, M R; Kass, P H

1994-01-01

Surgical submissions from canine splenectomy cases spanning a 3-year period (1988-1990) were evaluated. Eighty seven neoplasms of the spleen considered to be of nonangiomatous and nonlymphomatous origin were selected for morphologic classification, mitotic index determination, immunohistochemical analysis, and patient survival determination. In 76/87 cases, patient survival information was available, and the mitotic index was determined in 83/87 cases. Immunohistochemistry for selected antigens (vimentin, desmin, smooth muscle actin, myosin, and factor VIII-related antigen) was performed in 58/87 of the cases. Morphologic classification of these lesions in standard HE preparations yielded the following neoplastic groups: fibrosarcoma (19/87), undifferentiated sarcoma (19/87), leiomyosarcoma (14/87), osteosarcoma (8/87), mesenchymoma (7/87), myxosarcoma (6/87), histiocytic sarcoma (6/87), leiomyoma (3/87), lipoma-myelolipoma (2/87), liposarcoma (2/87), and malignant fibrous histiocytoma (1/87). A lack of distinct morphologic characteristics among many of the neoplasms that were classified as either fibrosarcoma, leiomyosarcoma, or undifferentiated sarcoma contrasted these groups with the relatively unambiguous features that distinguished the other sarcoma groups. Using immunohistochemical staining for muscle-specific antigens (desmin, smooth muscle actin, and myosin), specific staining often overlapped extensively within the neoplastic groups of fibrosarcomas, leiomyosarcomas, and undifferentiated sarcomas, suggesting either ambiguous morphologic findings or the possibility of a common histogenesis from smooth muscle trabeculae or a distinct population of splenic myofibroblasts. The biological behavior of all tumors examined could be placed into three categories of patient survival: (1) benign, noninvasive tumors (leiomyoma, lipoma) with prolonged survival intervals; (2) malignant tumors (fibrosarcoma, undifferentiated sarcoma, leiomyosarcoma, osteosarcoma, myxosarcoma, histiocytic sarcoma, and liposarcoma), showing severely truncated survival (median 4 months with 80-100% mortality after 12 months; and (3) intermediate survival periods (median 12 months with 50% 1 year survival) attributed to a single group of neoplasm, the mesenchymomas. The biological behavior of primary splenic nonangiomatous, nonlymphomatous sarcomas was most closely correlated with observed mitotic index. Splenic neoplasms of this type with a mitotic index < 9 showed significantly (P < 0.0001) longer survival intervals than those with an index > 9. With the exception of osteosarcoma, all anatomically defined tumor groups contained one or more specimens with a mitotic index < 9. The clinical prognosis given for splenic sarcomas should be modified according to the mitotic index as a predictive value for patient survival.

Intracellular delivery and passive tumor targeting of a self-assembled nanogel containing carborane clusters for boron neutron capture therapy.

PubMed

Kawasaki, Riku; Sasaki, Yoshihiro; Akiyoshi, Kazunari

2017-01-29

Boron neutron capture therapy, based on the release of thermal neutron irradiation from boron, is a targeted radiation therapy for cancer. Targeted and sufficient accumulation of boron in tumor cells to achieve cytotoxic efficacy and reduce off-target effects remains a challenge. Carborane has been investigated for use as a delivery agent in boron neutron capture therapy because of its high boron content and chemical stability; however, it is cytotoxic, making safe delivery difficult. The aim of this study was to investigate the potential of carborane-bearing pullulan nanogels to safely and effectively deliver boron to tumor cells in vitro and in vivo and, consequently, assess their potential as a boron neutron capture therapeutic. Murine fibrosarcoma cells (CMS5a) were used for in vitro investigations of nanogel cytotoxicity, cell uptake. A mouse fibrosarcoma xenograft model was used to investigate the bio-distribution of nanogels after intravenous administration. The nanogels produced no apparent cytotoxicity and underwent cell uptake in CMS5a cells after a 24 h incubation at up to 2000 μg/mL and 400 μg/mL, respectively. The internalized nanogels were localized around the nuclear membrane. The nanogels were administered intravenously to mice bearing fibrosarcoma xenografts. Nanogel tumor localization likely occurred through the enhanced permeation and retention effect. The nanogels successfully reduced the cytotoxicity of carborane, were internalized into tumor cells, acted as a dual-delivery therapeutic and accumulated in tumors in vivo. Consequently, they demonstrate significant potential as a boron neutron capture therapeutic. Copyright © 2016 Elsevier Inc. All rights reserved.

Synthesis and evaluation of Tc-99m-labeled RRL-containing peptide as a non-invasive tumor imaging agent in a mouse fibrosarcoma model.

PubMed

Kim, Dae-Weung; Kim, Woo Hyoung; Kim, Myoung Hyoun; Kim, Chang Guhn

2015-11-01

Arginine-arginine-leucine (RRL) is considered a tumor endothelial cell-specific binding sequence. RRL-containing peptide targeting tumor vessels is an excellent candidate for tumor imaging. In this study, we developed RRL-containing hexapeptides and evaluated their feasibility as a tumor imaging agent in a HT-1080 fibrosarcoma-bearing murine model. The hexapeptide, glutamic acid-cysteine-glycine (ECG)-RRL was synthesized using Fmoc solid-phase peptide synthesis. Radiolabeling efficiency was evaluated using instant thin-layer chromatography. Uptake of Tc-99m ECG-RRL within HT-1080 cells was evaluated in vitro by confocal microscopy and cellular binding affinity was calculated. Gamma images were acquired In HT-1080 fibrosarcoma tumor-bearing mice, and the tumor-to-muscle uptake ratio was calculated. The inflammatory-to-normal muscle uptake ratio was also calculated in an inflammation mouse model. A biodistribution study was performed to calculate %ID/g. A high yield of Tc-99m ECG-RRL complexes was prepared after Tc-99m radiolabeling. Binding of Tc-99m ECG-RRL to tumor cells had was confirmed by in vitro studies. Gamma camera imaging in the murine model showed that Tc-99m ECG-RRL accumulated substantially in the subcutaneously engrafted tumor and that tumoral uptake was blocked by co-injecting excess RRL. Moreover, Tc-99m ECG-RRL accumulated minimally in inflammatory lesions. We successfully developed Tc-99m ECG-RRL as a new tumor imaging candidate. Specific tumoral uptake of Tc-99m ECG-RRL was evaluated both in vitro and in vivo, and it was determined to be a good tumor imaging candidate. Additionally, Tc-99m ECG-RRL effectively distinguished between cancerous tissue and inflammatory lesions.

Impedimetric Analysis of the Effect of Decellularized Porcine Heart Scaffold on Human Fibrosarcoma, Endothelial, and Cardiomyocyte Cell Lines

PubMed Central

Bäcker, Henrik; Polgár, Livia; Soós, Pal; Lajkó, Eszter; Láng, Orsolya; Merkely, Bela; Szabó, Gabor; Dohmen, Pascal M.; Weymann, Alexander; Kőhidai, Laszlo

2017-01-01

Background Experiments on porcine heart scaffold represent significant assays in development of immunoneutral materials for cardiac surgery. Characterization of cell-cell and cell-scaffold interactions is essential to understand the homing process of cardiac cells into the scaffolds. Material/Methods In the present study, the highly sensitive and real-time impedimetric technique of xCELLigence SP was used to monitor cell adhesion, which is the key process of recellularization in heart scaffolds. Our objectives were: (i) to characterize the effect of decellularized porcine heart scaffold on cell adhesion of human cardiovascular cells potentially used in the recellularization process; and (ii) to investigate cell-extracellular matrix element interactions for building artificial multi-layer systems, applied as cellular models of recellularization experiments. Human fibrosarcoma, endothelial, and cardiomyocyte cells were investigated and the effect of decellularized porcine heart scaffold (HS) and fibronectin on cell adhesion was examined. Adhesion was quantified as slope of curves. Results Heart scaffold had neutral effect on cardiomyocytes as well as on endothelial cells. Adhesion of cardiomyocytes was increased by fibronectin (1.480±0.021) compared to control (0.745±0.029). The combination of fibronectin and HS induced stronger adhesion of cardiomyocytes (2.407±0.634) than fibronectin alone. Endothelial and fibrosarcoma cells showed similarly strong adhesion profiles with marked enhancer effect by fibronectin. Conclusions Decellularized porcine HS does not inhibit adhesion of human cardiovascular cells at the cell biological level, while fibronectin has strong cell adhesion-inducer effect, as well as an enhancer effect on activity of HS. Consequently, decellularized porcine hearts could be used as scaffolds for recellularization with cardiomyocytes and endothelial cells with fibronectin acting as a regulator, leading to construction of working bioartificial hearts. PMID:28493851

Pseudolaric Acid B Induced Cell Cycle Arrest, Autophagy and Senescence in Murine Fibrosarcoma L929 Cell

PubMed Central

hua Yu, Jing; yu Liu, Chun; bin Zheng, Gui; Zhang, Li Ying; hui Yan, Ming; yan Zhang, Wen; ying Meng, Xian; fang Yu, Xiao

2013-01-01

Objective: PAB induced various cancer cell apoptosis, cell cycle arrest and senescence. But in cell line murine fibrosarcoma L929, PAB did not induce apoptosis, but autophagy, therefore it was thought by us as a good model to research the relationship of cell cycle arrest, autophagy and senescence bypass apoptosis. Methods: Inhibitory ratio was assessed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) analysis. Phase contrast microscopy visualized cell morphology. Hoechst 33258 staining for nuclear change, propidium iodode (PI) staining for cell cycle, monodansylcadaverine (MDC) staining for autophagy, and rodanmine 123 staining for mitochondrial membrane potential (MMP) were measured by fluorescence microscopy or flowcytometry. Apoptosis was determined by DNA ladder test. Protein kinase C (PKC) activity was detected by PKC assay kit. SA-β-galactosidase assay was used to detect senescence. Protein expression was examined by western blot. Results: PAB inhibited L929 cell growth in time-and dose-dependent manner. At 12 h, 80 μmol/L PAB induced obvious mitotic arrest; at 24 h, PAB began to induce autophagy; at 36 h, cell-treated with PAB slip into G1 cell cycle; and 3 d PAB induced senescence. In time sequence PAB induced firstly cell cycle arrest, then autophagy, then slippage into G1 phase, lastly senescence. Senescent cells had high level of autophagy, inhibiting autophagy led to apoptosis, and no senescence. PAB activated PKC activity to induce cell cycle arrest, autophagy and senescence, inhibiting PKC activity suppressed cell cycle arrest, autophagy and senescence. Conclusion: PAB induced cell cycle arrest, autophagy and senescence in murine fibrosarcoma L929 cell through PKC. PMID:23630435

Exposure Standard for Fog Oil

DTIC Science & Technology

1990-11-15

painting thrice weekly for 15 weeks with a non-carcinogenic batch of Jute oil induced benign papillomas, keratoacanthoinas and fibrosarcomas . Agarw;l et...granulomas and pneumonias, following 91a13o5repeated nasal administration of food or medicinal grade mineral oils. *, ,3 3 Scattered case reports

Exosome secretion promotes chemotaxis of cancer cells.

PubMed

Sung, Bong Hwan; Weaver, Alissa M

2017-03-04

Migration of cells toward chemical cues, or chemotaxis, is important for many biologic processes such as immune defense, wound healing and cancer metastasis. Although chemotaxis is thought to occur in cancer cells, it is less well characterized than chemotaxis of professional immune cells such as neutrophils. Here, we show that cancer cell chemotaxis relies on secretion of exosome-type extracellular vesicles. Migration of fibrosarcoma cells toward a gradient of exosome-depleted serum was diminished by knockdown of the exosome secretion regulator Rab27a. Rescue experiments in which chemotaxis chambers were coated with purified extracellular vesicles demonstrate that exosomes but not microvesicles affect both speed and directionality of migrating cells. Chamber coating with purified fibronectin and fibronectin-depleted exosomes demonstrates that the exosome cargo fibronectin promotes cell speed but cannot account for the role of exosomes in promoting directionality of fibrosarcoma cell movement during chemotaxis. These experiments indicate that exosomes contain multiple motility-promoting cargoes that contribute to different aspects of cell motility.

Production of interferon-gamma by in vivo tumor-sensitized T cells: Association with active antitumor immunity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bursuker, I.; Pearce, M.T.

1990-02-01

The state of active immunity to Meth A fibrosarcoma in mice immunized with an admixture of Meth A cells and Propionibacterium acnes is associated with possession by the host of spleen cells capable of producing interferon-gamma (IFN-gamma) upon in vitro restimulation with irradiated tumor cells. The ability of spleen cells from immunized mice to produce IFN-gamma in response to irradiated Meth A cells decays as active antitumor immunity is replaced by a state of immunological memory. The IFN-producing cells are L3T4+Ly2+, cyclophosphamide-sensitive and radiosensitive T cells, as determined by their sensitivity to corresponding monoclonal antibodies and complement. The induction ofmore » IFN-gamma production by in vivo tumor-sensitized T cells is tumor specific, in that spleen cells from mice immunized against Meth A fibrosarcoma can produce IFN in response to irradiated Meth A cells but not in response to another syngeneic tumor M109 lung carcinoma.« less

Pulmonary and mediastinal metastases of a vaccination-site sarcoma in a cat.

PubMed

Rudmann, D G; Van Alstine, W G; Doddy, F; Sandusky, G E; Barkdull, T; Janovitz, E B

1996-07-01

Sarcomas at vaccination sites in cats were first reported in 1992. Recent retrospective studies have confirmed an association between these vaccination-site sarcomas (VSS) and feline leukemia virus (FeLV) and/ or rabies vaccines. In most cases, VSS are locally invasive fibrosarcomas that tend to recur but rarely metastasize. We report the mediastinal and pulmonary metastases of a VSS in a FeLV-and feline immunodeficiency virus-negative, 8-year-old, domestic short-haired cat. The primary sarcoma was removed from an interscapular vaccination site and diagnosed as a VSS 3 months prior to radiographic lesions suggestive of pulmonary and mediastinal metastases. At necropsy, there were multiple pulmonary and mediastinal nodules that histologically and ultrastructurally were fibrosarcomas, cytomorphologically similar to the VSS. In addition, immunohistochemical staining patterns of the VSS and metastatic sites were consistent with that described for VSS. Recent reports of pulmonary and mediastinal metastases of interscapular VSS emphasize the importance of early diagnosis and treatment of these tumors.

Laminin-111 peptide C16 regulates invadopodia activity of malignant cells through β1 integrin, Src and ERK 1/2.

PubMed

Siqueira, Adriane S; Pinto, Monique P; Cruz, Mário C; Smuczek, Basilio; Cruz, Karen S P; Barbuto, José Alexandre M; Hoshino, Daisuke; Weaver, Alissa M; Freitas, Vanessa M; Jaeger, Ruy G

2016-07-26

Laminin peptides influence tumor behavior. In this study, we addressed whether laminin peptide C16 (KAFDITYVRLKF, γ1 chain) would increase invadopodia activity of cells from squamous cell carcinoma (CAL27) and fibrosarcoma (HT1080). We found that C16 stimulates invadopodia activity over time in both cell lines. Rhodamine-conjugated C16 decorates the edge of cells, suggesting a possible binding to membrane receptors. Flow cytometry showed that C16 increases activated β1 integrin, and β1 integrin miRNA-mediated depletion diminishes C16-induced invadopodia activity in both cell lines. C16 stimulates Src and ERK 1/2 phosphorylation, and ERK 1/2 inhibition decreases peptide-induced invadopodia activity. C16 also increases cortactin phosphorylation in both cells lines. Based on our findings, we propose that C16 regulates invadopodia activity over time of squamous carcinoma and fibrosarcoma cells, probably through β1 integrin, Src and ERK 1/2 signaling pathways.

A novel branched TAT(47-57) peptide for selective Ni(2+) introduction into the human fibrosarcoma cell nucleus.

PubMed

Szyrwiel, Łukasz; Shimura, Mari; Shirataki, Junko; Matsuyama, Satoshi; Matsunaga, Akihiro; Setner, Bartosz; Szczukowski, Łukasz; Szewczuk, Zbigniew; Yamauchi, Kazuto; Malinka, Wiesław; Chavatte, Laurent; Łobinski, Ryszard

2015-07-01

A TAT47-57 peptide was modified on the N-terminus by elongation with a 2,3-diaminopropionic acid residue and then by coupling of two histidine residues on its N-atoms. This branched peptide could bind to Ni under physiological conditions as a 1 : 1 complex. We demonstrated that the complex was quantitatively taken up by human fibrosarcoma cells, in contrast to Ni(2+) ions. Ni localization (especially at the nuclei) was confirmed by imaging using both scanning X-ray fluorescence microscopy and Newport Green fluorescence. A competitive assay with Newport Green showed that the latter displaced the peptide ligand from the Ni-complex. Ni(2+) delivered as a complex with the designed peptide induced substantially more DNA damage than when introduced as a free ion. The availability of such a construct opens up the way to investigate the importance of the nucleus as a target for the cytotoxicity, genotoxicity or carcinogenicity of Ni(2+).

Congenital Fibrosarcoma and History of Prenatal Exposure to Petroleum Derivatives

PubMed Central

Soldin, Offie P.; López-Hernández, Fernando A.; Trasande, Leonardo; Ferrís-Tortajada, Josep

2012-01-01

Congenital fibrosarcoma (CFS) is a rare fibrous tissue malignancy that usually presents in the first few years of life. It is unique among human sarcomas in that it has an excellent prognosis. We describe a temporal clustering of a number of cases of CFS and investigate the possible associated prenatal risk factors. The Pediatric Environmental History, a questionnaire developed in our clinic that is instrumental in determining environmental risk factors for tumor-related disease, was essential in documenting the presence or absence of risk factors considered as human carcinogens. We found a history of exposure to petroleum products in four cases of CFS that occurred at a greater than expected rate in a short time frame–an apparent cancer cluster. We call attention to the possibility that exposure to petroleum products raises the risk of developing CFS. While future studies should focus on systematic investigation of CFS and its underlying mechanisms, this report suggests the need for proactive measures to avoid exposure to solvents and petroleum products during pregnancy. PMID:22945410

Ribociclib and Doxorubicin in Treating Patients With Metastatic or Advanced Soft Tissue Sarcomas That Cannot Be Removed by Surgery

ClinicalTrials.gov

2018-05-09

Metastatic Angiosarcoma; Metastatic Epithelioid Sarcoma; Metastatic Fibrosarcoma; Metastatic Leiomyosarcoma; Metastatic Liposarcoma; Metastatic Malignant Peripheral Nerve Sheath Tumor; Metastatic Synovial Sarcoma; Metastatic Undifferentiated Pleomorphic Sarcoma; Myxofibrosarcoma; Pleomorphic Rhabdomyosarcoma; Stage III Soft Tissue Sarcoma; Stage IV Soft Tissue Sarcoma; Undifferentiated (Embryonal) Sarcoma

Prostaglandin E2 Regulation of Chondrocyte Proliferation and Differentiation

DTIC Science & Technology

1994-05-01

lipopolysaccharide- and TNF-induced cartilage breakdown in bovine nasal cartilage(121’. The use of medications that modulate PGE2 production may have an adverse...Levine, P. Goldhaber. 1972. Evidence that the bone resorption stimulating factor produced by mouse fibrosarcoma cells is prostaglandin E2. J. Exp. Med

Bibliography of Scientific Publications 1977-1991.

DTIC Science & Technology

1992-06-01

A.R., " Nasal Adenocarcinoma in a Taiwan Macaque." Veterinary Pathology, Vol. 14., pp. 294-296, 1977. Brown, RJ., Kessler, MJ., and Kupper, J.L...34Myocardial Fibrosarcoma in Rhesus Monkey." Laboratory Animal Science, Vol. 27, pp. 524-525, 1977. Carney, W.P., Brown, RJ., Van Peenen, P.F.D., Purnomo

Development of Carcinogenesis Bioassay Models: Response of Small Fish Species to Various Classes of Carcinogens

DTIC Science & Technology

1989-12-14

induces injection-site sarcomas (mainly fibrosarcomas and rhabdomyosarcomas) as well as reproductive toxicity and neoplasms in males (Haddow et al...G., and Ward, J.M., 1981. Characteristics of proliferative lesions in the nasal cavities of mice following chronic inhalation of EDB. Cancer Lett., 12

Studying Genes in Tissue Samples From Younger and Adolescent Patients With Soft Tissue Sarcomas

ClinicalTrials.gov

2016-05-13

Childhood Alveolar Soft-part Sarcoma; Childhood Angiosarcoma; Childhood Desmoplastic Small Round Cell Tumor; Childhood Epithelioid Sarcoma; Childhood Fibrosarcoma; Childhood Leiomyosarcoma; Childhood Liposarcoma; Childhood Malignant Mesenchymoma; Childhood Neurofibrosarcoma; Childhood Synovial Sarcoma; Chordoma; Desmoid Tumor; Metastatic Childhood Soft Tissue Sarcoma; Nonmetastatic Childhood Soft Tissue Sarcoma; Recurrent Childhood Soft Tissue Sarcoma

Temporal Control of Transforming Growth Factor (TGF) - Betal Expression on Mammary Cell Multistep Transformation

DTIC Science & Technology

1999-10-01

deregulated cell mors and may eventually regress through growth (18). The importance of APC and 0- cat - apoptosis (25). enin in the development of colorectal...progression. In support of this idea, Torre Amione et al. [74] demonstrated that, unlike parental tumor cells, fibrosarcoma cells transfected to express 10

Radiation-induced antrochoanal fibrosarcoma.

PubMed

Liddington, M I; Harrison, R F; Booth, A P; Das Gupta, A R

1992-06-01

Therapeutic radiation for malignant conditions is known to cause sarcomatous change in an irradiated field after a latent period; equally this change may occur following radiotherapy to benign conditions which may result in a more difficult management problem later. Radiotherapy to benign conditions should be reserved for use after failure of conventional surgery or other interventional techniques.

Stawamycin analog, JBIR-11 from Streptomyces viridochromogenes subsp. sulfomycini NBRC 13830.

PubMed

Izumikawa, Miho; Komaki, Hisayuki; Hashimoto, Junko; Takagi, Motoki; Shin-ya, Kazuo

2008-05-01

A stawamycin analog, JBIR-11 (1) was isolated from mycelium of Streptomyces viridochromogenes subsp. sulfomycini NBRC 13830. The structure was determined on the basis of the spectroscopic data. Compound 1 exhibited growth inhibitory effect against human fibrosarcoma HT1080 cells with an IC50 value of 25 microM.

To Find a Safe Dose and Show Early Clinical Activity of Weekly Nab-paclitaxel in Pediatric Patients With Recurrent/ Refractory Solid Tumors

ClinicalTrials.gov

2018-04-23

Neuroblastoma; Rhabdomyosarcoma; Ewing's Sarcoma; Ewing's Tumor; Sarcoma, Ewing's; Sarcomas, Epitheliod; Sarcoma, Soft Tissue; Sarcoma, Spindle Cell; Melanoma; Malignant Melanoma; Clinical Oncology; Oncology, Medical; Pediatrics, Osteosarcoma; Osteogenic Sarcoma; Osteosarcoma Tumor; Sarcoma, Osteogenic; Tumors; Cancer; Neoplasia; Neoplasm; Histiocytoma; Fibrosarcoma; Dermatofibrosarcoma

Cixutumumab and Temsirolimus in Treating Younger Patients With Recurrent or Refractory Sarcoma

ClinicalTrials.gov

2018-03-21

Childhood Alveolar Soft Part Sarcoma; Childhood Angiosarcoma; Childhood Epithelioid Sarcoma; Childhood Fibrosarcoma; Childhood Gliosarcoma; Childhood Leiomyosarcoma; Childhood Liposarcoma; Childhood Malignant Peripheral Nerve Sheath Tumor; Childhood Synovial Sarcoma; Previously Treated Childhood Rhabdomyosarcoma; Recurrent Childhood Rhabdomyosarcoma; Recurrent Childhood Soft Tissue Sarcoma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Osteosarcoma; Rhabdomyosarcoma

Seahorse-derived peptide suppresses invasive migration of HT1080 fibrosarcoma cells by competing with intracellular α-enolase for plasminogen binding and inhibiting uPA-mediated activation of plasminogen.

PubMed

Kim, Yong-Tae; Kim, Se-kwon; Jeon, You-Jin; Park, Sun Joo

2014-12-01

α-Enolase is a glycolytic enzyme and a surface receptor for plasminogen. α-Enolase-bound plasminogen promotes tumor cell invasion and cancer metastasis by activating plasmin and consequently degrading the extracellular matrix degradation. Therefore, α-enolase and plasminogen are novel targets for cancer therapy. We found that the amino acid sequence of a peptide purified from enzymatic hydrolysates of seahorse has striking similarities to that of α-enolase. In this study, we report that this peptide competes with cellular α-enolase for plasminogen binding and suppresses urokinase plasminogen activator (uPA)-mediated activation of plasminogen, which results in decreased invasive migration of HT1080 fibrosarcoma cells. In addition, the peptide treatment decreased the expression levels of uPA compared to that of untreated controls. These results provide new insight into the mechanism by which the seahorse-derived peptide suppresses invasive properties of human cancer cells. Our findings suggest that this peptide could emerge as a potential therapeutic agent for cancer.

Seahorse-derived peptide suppresses invasive migration of HT1080 fibrosarcoma cells by competing with intracellular α-enolase for plasminogen binding and inhibiting uPA-mediated activation of plasminogen

PubMed Central

Kim, Yong-Tae; Kim, Se-kwon; Jeon, You-Jin; Park, Sun Joo

2014-01-01

α-Enolase is a glycolytic enzyme and a surface receptor for plasminogen. α-Enolase-bound plasminogen promotes tumor cell invasion and cancer metastasis by activating plasmin and consequently degrading the extracellular matrix degradation. Therefore, α-enolase and plasminogen are novel targets for cancer therapy. We found that the amino acid sequence of a peptide purified from enzymatic hydrolysates of seahorse has striking similarities to that of α-enolase. In this study, we report that this peptide competes with cellular α-enolase for plasminogen binding and suppresses urokinase plasminogen activator (uPA)-mediated activation of plasminogen, which results in decreased invasive migration of HT1080 fibrosarcoma cells. In addition, the peptide treatment decreased the expression levels of uPA compared to that of untreated controls. These results provide new insight into the mechanism by which the seahorse-derived peptide suppresses invasive properties of human cancer cells. Our findings suggest that this peptide could emerge as a potential therapeutic agent for cancer. [BMB Reports 2014; 47(12): 691-696] PMID:24602611

Transcriptional response of peripheral lymphocytes to early fibrosarcoma: a model system for cancer detection based on hybridization signatures.

PubMed

Marques, Márcia M C; Junta, Cristina M; Zárate-Blades, Carlos R; Sakamoto-Hojo, Elza Tiemi; Donadi, Eduardo A; Passos, Geraldo A S

2009-07-01

Since circulating leukocytes, mainly B and T cells, continuously maintain vigilant and comprehensive immune surveillance, these cells could be used as reporters for signs of infection or other pathologies, including cancer. Activated lymphocyte clones trigger a sensitive transcriptional response, which could be identified by gene expression profiling. To assess this hypothesis, we conducted microarray analysis of the gene expression profile of lymphocytes isolated from immunocompetent BALB/c mice subcutaneously injected with different numbers of tumorigenic B61 fibrosarcoma cells. Flow cytometry demonstrated that the number of circulating T (CD3(+)CD4(+) or CD3(+)CD8(+)) or B (CD19(+)) cells did not change. However, the lymphocytes isolated from tumor cell-injected animals expressed a unique transcriptional profile that was identifiable before the development of a palpable tumor mass. This finding demonstrates that the transcriptional response appears before alterations in the main lymphocyte subsets and that the gene expression profile of peripheral lymphocytes can serve as a sensitive and accurate method for the early detection of cancer.

CGP 55398, a liposomal Ge(IV) phthalocyanine bearing two axially ligated cholesterol moieties: a new potential agent for photodynamic therapy of tumours.

PubMed Central

Segalla, A.; Milanesi, C.; Jori, G.; Capraro, H. G.; Isele, U.; Schieweck, K.

1994-01-01

Ge(IV) phthalocyanine (GePc) with two axially ligated cholesterol moieties was prepared by chemical synthesis and incorporated in a monomeric state into small unilamellar liposomes (CGP 55398). Upon photoexcitation with light wavelengths around its intense absorption peak at 680 nm, GePc shows an efficient photosensitising activity towards biological substrates through a mechanism which largely involves the intermediacy of singlet oxygen. GePc injected systemically into mice bearing an intramuscularly implanted MS-2 fibrosarcoma is quantitatively transferred to serum lipoproteins and localises in the tumour tissue with good efficiency: at 24 h post injection the GePc content in the tumour is 0.74 and 1.87 micrograms per g of tissue with a tumour/peritumoral ratio of 4.35 and 5.67 for injected doses of 0.76 and 1.52 mg kg-1 respectively. At this time the red-light irradiation of the GePc-loaded fibrosarcoma causes a fast and massive tumour necrosis involving both malignant cells and blood vessels. Images Figure 8 Figure 9 Figure 10 Figure 11 Figure 12 PMID:8180009

Biological study of the effect of water soluble [N-(2-hydroxybenzyl)-L-aspartato] gallium complexes on breast carcinoma and fibrosarcoma cells.

PubMed

Mohsen, Ahmed; Saby, Charles; Collery, Philippe; Sabry, Gilane Mohamed; Hassan, Rasha Elsherif; Badawi, Abdelfattah; Jeannesson, Pierre; Desmaële, Didier; Morjani, Hamid

2016-10-01

Two water soluble gallium complexes described as [Ga(III)LCl], where L is the deprotonated form of N-2-hydroxybenzyl aspartic acid derivatives, were synthesized and characterized by (1)H NMR, (13)C NMR, FT-IR, mass spectrometry, and elemental analysis. The 2-(5-chloro-2-hydroxybenzylamino)succinic acid derivative (GS2) has been found to be a promising anticancer drug candidate. This compound was found to be more cytotoxic against human breast carcinoma MDA-MB231 and fibrosarcoma HT-1080 cell lines than the unsubstituted derivative and GaCl3. GS2 was able to induce apoptosis through downregulation of AKT phosphorylation, G2M arrest in cell cycle, and caspase 3/7 pathway. This gallium complex was found to induce an increase in mitochondrial ROS level in HT-1080 cells but not in MDA-MB231 cells. This suggests that the mechanism of action of GS2 would not be mediated by the drug-induced oxidative stress but probably by directly and indirectly inhibiting the AKT cell-signaling pathway.

Radiation therapy and surgery for fibrosarcoma in 33 cats.

PubMed

Cronin, K; Page, R L; Spodnick, G; Dodge, R; Hardie, E N; Price, G S; Ruslander, D; Thrall, D E

1998-01-01

Thirty-three cats with histologically confirmed fibrosarcomas were treated with radiation therapy followed by surgery. The median (95% confidence interval) disease free interval and overall survival were 398 (261,924) and 600 (lower limit 515) days, respectively. There were 19 treatment failures; 11 cats had only local recurrence, 4 cats developed metastatic disease, 3 cats had local recurrence followed by metastasis, and 1 cat developed simultaneous local and distant disease. Twelve cats are alive and disease free. Two cats died without evidence of treatment failure. The presence of tumor cells at the margin of resected tissue after radiation was the only variable which influenced treatment success. The median (95% confidence interval) disease free interval in 5 cats with tumor cells at the margin of the resected specimen was 112 (94,150) days versus 700 (lower limit 328) days for 26 cats with negative tumor margins, p < 0.0001. We did not identify a relationship between tumor volume, number of prior tumor excisions, concomitant use of chemotherapy or various descriptors of the radiation therapy technique and disease free interval.

Regulation of adhesion and growth of fibrosarcoma cells by NF-kappa B RelA involves transforming growth factor beta.

PubMed Central

Perez, J R; Higgins-Sochaski, K A; Maltese, J Y; Narayanan, R

1994-01-01

The NF-kappa B transcription factor is a pleiotropic activator that participates in the induction of a wide variety of cellular genes. Antisense oligomer inhibition of the RelA subunit of NF-kappa B results in a block of cellular adhesion and inhibition of tumor cell growth. Investigation of the molecular basis for these effects showed that in vitro inhibition of the growth of transformed fibroblasts by relA antisense oligonucleotides can be reversed by the parental-cell-conditioned medium. Cytokine profile analysis of these cells treated with relA antisense oligonucleotides revealed inhibition of transforming growth factor beta 1 (TGF-beta 1 to the transformed fibroblasts reversed the inhibitory effects of relA antisense oligomers on soft agar colony formation and cell adhesion to the substratum. Direct inhibition of TGF-beta 1 expression by antisense phosphorothioates to TGF-beta 1 mimicked the in vitro effects of blocking cell adhesion that are elicited by antisense relA oligomers. These results may explain the in vitro effects of relA antisense oligomers on fibrosarcoma cell growth and adhesion. Images PMID:8035811

DNA-hypomethylating agent, 5'-azacytidine, induces cyclooxygenase-2 expression via the PI3-kinase/Akt and extracellular signal-regulated kinase-1/2 pathways in human HT1080 fibrosarcoma cells.

PubMed

Yu, Seon-Mi; Kim, Song-Ja

2015-10-01

The cytosine analogue 5'-azacytidine (5'-aza) induces DNA hypomethylation by inhibiting DNA methyltransferase. In clinical trials, 5'-aza is widely used in epigenetic anticancer treatments. Accumulated evidence shows that cyclooxygenase-2 (COX-2) is overexpressed in various cancers, indicating that it may play a critical role in carcinogenesis. However, few studies have been performed to explore the molecular mechanism underlying the increased COX-2 expression. Therefore, we tested the hypothesis that 5'-aza regulates COX-2 expression and prostaglandin E2 (PGE2) production. The human fibrosarcoma cell line HT1080, was treated with various concentrations of 5'-aza for different time periods. Protein expressions of COX-2, DNA (cytosine-5)-methyltransferase 1 (DNMT1), pAkt, Akt, extracellular signal-regulated kinase (ERK), and phosphorylated ERK (pERK) were determined using western blot analysis, and COX-2 mRNA expression was determined using RT-PCR. PGE2 production was evaluated using the PGE2 assay kit. The localization and expression of COX-2 were determined using immunofluorescence staining. Treatment with 5'-aza induces protein and mRNA expression of COX-2. We also observed that 5'-aza-induced COX-2 expression and PGE2 production were inhibited by S-adenosylmethionine (SAM), a methyl donor. Treatment with 5'-aza phosphorylates PI3-kinase/Akt and ERK-1/2; inhibition of these pathways by LY294002, an inhibitor of PI3-kinase/Akt, or PD98059, an inhibitor of ERK-1/2, respectively, prevents 5'-aza-induced COX-2 expression and PGE2 production. Overall, these observations indicate that the hypomethylating agent 5'-aza modulates COX-2 expression via the PI3-kinase/Akt and ERK-1/2 pathways in human HT1080 fibrosarcoma cells.

Intracellular delivery and passive tumor targeting of a self-assembled nanogel containing carborane clusters for boron neutron capture therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kawasaki, Riku; JST-ERATO, Japan Science and Technology Agency; Sasaki, Yoshihiro

Boron neutron capture therapy, based on the release of thermal neutron irradiation from boron, is a targeted radiation therapy for cancer. Targeted and sufficient accumulation of boron in tumor cells to achieve cytotoxic efficacy and reduce off-target effects remains a challenge. Carborane has been investigated for use as a delivery agent in boron neutron capture therapy because of its high boron content and chemical stability; however, it is cytotoxic, making safe delivery difficult. The aim of this study was to investigate the potential of carborane-bearing pullulan nanogels to safely and effectively deliver boron to tumor cells in vitro and in vivo and,more » consequently, assess their potential as a boron neutron capture therapeutic. Murine fibrosarcoma cells (CMS5a) were used for in vitro investigations of nanogel cytotoxicity, cell uptake. A mouse fibrosarcoma xenograft model was used to investigate the bio-distribution of nanogels after intravenous administration. The nanogels produced no apparent cytotoxicity and underwent cell uptake in CMS5a cells after a 24 h incubation at up to 2000 μg/mL and 400 μg/mL, respectively. The internalized nanogels were localized around the nuclear membrane. The nanogels were administered intravenously to mice bearing fibrosarcoma xenografts. Nanogel tumor localization likely occurred through the enhanced permeation and retention effect. The nanogels successfully reduced the cytotoxicity of carborane, were internalized into tumor cells, acted as a dual-delivery therapeutic and accumulated in tumors in vivo. Consequently, they demonstrate significant potential as a boron neutron capture therapeutic. - Highlights: • A carborane-bearing pullulan nanogel is developed as a boron delivery agent. • The nanogels are cell-friendly and show effective cell uptake for drug delivery. • The nanogels show passive tumor targeting by enhanced permeation and retention.« less

Intra-tumoral gene delivery of feIL-2, feIFN-gamma and feGM-CSF using magnetofection as a neoadjuvant treatment option for feline fibrosarcomas: a phase-I study.

PubMed

Jahnke, A; Hirschberger, J; Fischer, C; Brill, T; Köstlin, R; Plank, C; Küchenhoff, H; Krieger, S; Kamenica, K; Schillinger, U

2007-12-01

Despite aggressive pre- or postoperative treatment, feline fibrosarcomas have a high relapse rate. In this study, a new treatment option based on immune stimulation by intra-tumoral delivery of three feline cytokine genes was performed. The objective of this phase-I dose-escalation study was to determine a safe dose for further evaluation in a subsequent phase-II trial. Twenty-five client-owned cats with clinical diagnosis of fibrosarcoma - primary tumours as well as recurrences - entered the study. Four increasing doses of plasmids coding for feIL-2, feIFN-gamma or feGM-CSF, respectively, were previously defined. In groups I, II, III and IV these doses were 15, 50, 150 and 450 microg per plasmid and a corresponding amount of magnetic nanoparticles. Two preoperative intra-tumoral injections of the magnetic DNA solution were followed by magnetofection. A group of four control cats received only surgical treatment. Side effects were registered and graded according to the VCOG-CTCAE scale and correlated to treatment. Statistical analyses included one-way anova, post hoc and Kruskal-Wallis tests. ELISA tests detecting plasma feIFN-gamma and plasma feGM-CSF were performed. One cat out of group IV (450 microg per plasmid) showed adverse events probably related to gene delivery. As these side effects were self-limiting and occurred only in one of eight cats in group IV, this dose was determined to be well tolerable. Altogether six cats developed local recurrences during a 1-year observation period. Four of these cats had been treated with dose IV. Regarding these observations, a subsequent phase-II trial including a representative amount of cats should be tested for the efficacy of dose IV as well as dose III.

Transcription factor EGR-1 suppresses the growth and transformation of human HT-1080 fibrosarcoma cells by induction of transforming growth factor beta 1.

PubMed Central

Liu, C; Adamson, E; Mercola, D

1996-01-01

The early growth response 1 (EGR-1) gene product is a transcription factor with role in differentiation and growth. We have previously shown that expression of exogenous EGR-1 in various human tumor cells unexpectedly and markedly reduces growth and tumorigenicity and, conversely, that suppression of endogenous Egr-1 expression by antisense RNA eliminates protein expression, enhances growth, and promotes phenotypic transformation. However, the mechanism of these effects remained unknown. The promoter of human transforming growth factor beta 1 (TGF-beta 1) contains two GC-rich EGR-1 binding sites. We show that expression of EGR-1 in human HT-1080 fibrosarcoma cells uses increased secretion of biologically active TGF-beta 1 in direct proportion (rPearson = 0.96) to the amount of EGR-1 expressed and addition of recombinant human TGF-beta 1 is strongly growth-suppressive for these cells. Addition of monoclonal anti-TGF-beta 1 antibodies to EGR-1-expressing HT-1080 cells completely reverses the growth inhibitory effects of EGR-1. Reporter constructs bearing the EGR-1 binding segment of the TGF-beta 1 promoter was activated 4- to 6-fold relative to a control reporter in either HT-1080 cells that stably expressed or parental cells cotransfected with an EGR-1 expression vector. Expression of delta EGR-1, a mutant that cannot interact with the corepressors, nerve growth factor-activated factor binding proteins NAB1 and NAB2, due to deletion of the repressor domain, exhibited enhanced transactivation of 2- to 3.5-fold over that of wild-type EGR-1 showing that the reporter construct reflected the appropriate in vivo regulatory context. The EGR-1-stimulated transactivation was inhibited by expression of the Wilms tumor suppressor, a known specific DNA-binding competitor. These results indicate that EGR-1 suppresses growth of human HT-1080 fibrosarcoma cells by induction of TGF-beta 1. Images Fig. 1 Fig. 5 PMID:8876223

Synergistic effect of aged garlic extract and naltrexone on improving immune responses to experimentally induced fibrosarcoma tumor in BALB/c mice

PubMed Central

Ebrahimpour, Soheil; Tabari, Mohaddeseh Abouhosseini; Youssefi, Mohammad Reza; Aghajanzadeh, Hamid; Behzadi, Manijeh Yousefi

2013-01-01

Background: Garlic, a medicinal plant, and Naltrexone (NTX), an opioid receptor antagonist, both have immunomodulatory and antitumor effects. Current study was designed to evaluate synergistic antitumor effects of aged garlic extract (AGE) and NTX. Materials and Methods: WEHI-164 fibrosarcoma cells were implanted subcutaneously on day 0 into right flank of 80 BALB/c mice at age of 8 weeks. Mice were randomly categorized in four separate groups: The first group received AGE (100 mg/kg, i.p.), the second group received NTX (0.5 mg/kg, i.p.), the third group received both of them, and the fourth group received phosphate buffered saline as control group. Treatments were administered three times per week. Tumor growth was measured and morbidity was recorded. Subpopulations of CD4+/CD8+ T cells were determined using flowcytometery. WEHI-164 cell specific cytotoxicity of splenocytes and in vitro production of interferon-gamma (IFN-γ) and interleukin-4 (IL-4) cytokines were measured. All statistical analyses were conducted with SPSS 16 software and P < 0.05 was considered to be statistically significant. Results: The mice who received AGE+NTX had significantly longer survival time compared with the mice treated with AGE or NTX alone. An enhanced inhibitory effect on tumor growth was seen in combination therapy group. The CD4+/CD8+ ratio and in vitro IFN-γ production of splenocytes were significantly increased in AGE+NTX and NTX groups. WEHI-164 specific cytotoxicity of splenocytes was also significantly increased at 25:1 E:T ratio in AGE+NTX treated mice. Coadministration of AGE with NTX resulted in improvement of immune responses against experimentally implanted fibrosarcoma tumors in BALB/c mice. Conclusions: AGE showed synergistic effects with NTX on inhibition of tumor growth and increment of survival times. PMID:23901215

Temporal Control of Transforming Growth Factor (TGF) - Betal Expression on Mammary Cell Multistep Transformation

DTIC Science & Technology

2001-10-01

tu- vation of transcription and deregulated cell mors and may eventually regress through growth (18). The importance of APC and [- cat - apoptosis (25...receptors, fibrosarcoma cells transfected to express 10ng/ml TPRII [621, ALK-1 [63], and endoglin [64], and one of its TGF-131 in vitro are unable to

HER2 Oncogene-Induced DNA Damage Response as a Barrier that Must Be Overcome to Form Breast Tumors In Normal Mammary Epithelium

DTIC Science & Technology

2010-03-01

Ras-driven lung carcinoma and chemically induced fibrosarcoma murine models (16). In breast carcinogenesis, apoptosis and senescence were detected in...permeabilized in 0.1% Triton-X before staining. The manu- facturer’s protocol for the MOM, Vectastain Elite ABCRabbit, or Rat kits (Vector Labs; cat no. PK

Legubicin, a Tumor-Activated Prodrug for Breast Cancer Therapy

DTIC Science & Technology

2007-04-01

carcinomas, leukemias, lymphomas, melanomas, fibrosarcomas , neuroblastoma, and the like. The cancer can, for example, be autoimmune deficiency syndrome...their analogs. (a) 4-Nitrophenyl chloroformate, Py, CH2Cl2, 0°C; (b) (i) OsO4 ( cat ), NMO, citric acid, CH2Cl2-H2O (10:1), RT, (ii) NaIO4, THF- H2O (1:1

JPRS Report Science & Technology USSR: Life Sciences.

DTIC Science & Technology

1988-06-10

V.F. Shilina; GIGIYENA ISANITARIYA No 10, Oct 87] 14 PHYSIOLOGY Changes in Cerebral Electrical Activity of Cats After Intravenous and...from human fibrosarcoma , was studied and compared to expression in normal human leukocytes and slightly transformed cells from human melanoma line...06508 JPRS-ULS-88-009 10 June 1988 PHYSIOLOGY 15 Changes in Cerebral Electrical Activity of Cats After Intravenous and Cerebroventricular

[Aggressive fibromatosis of the nasal sinuses].

PubMed

Artazkoz del Toro, J J; Pons Rocher, F; Dalmau Galofré, J; Mompó Romero, L; Guallart Domènech, F; Serrano Badía, E

1994-01-01

A case report of a feminine patient who complained of nasal ventilatory obstruction and nasosinusal polyposis is presented. She underwent surgery and the pathological study revealed the existence of an aggressive fibromatosis. The AA. review the literature dealing with this illness and explain an update state of the clinical features, treatment and the course of this rare entity, closely related to fibrosarcoma.

Tumours of the soft (mesenchymal) tissues.

PubMed

Weiss, E

1974-01-01

This is a classification of tumours of fibrous tissue, fat, muscle, blood and lymph vessels, and mast cells, irrespective of the region of the body in which they arise. Tumours of fibrous tissue are divided into fibroma, fibrosarcoma (including "canine haemangiopericytoma"), other sarcomas, equine sarcoid, and various tumour-like lesions. The histological appearance of the tumours is described and illustrated with photographs.

Comparative activation states of tumor-associated and peritoneal macrophages from mice bearing an induced fibrosarcoma.

PubMed

Valdez, J C; de Alderete, N; Meson, O E; Sirena, A; Perdigon, G

1990-11-01

Balb/c mice bearing a methylcholanthrene-induced fibrosarcoma were used to compare the activation levels of tumor-associated and peritoneal macrophages. Two stages of tumor growth were examined, namely "small" and "large" tumors, with average diameters of 10 and 30 mm, respectively. The activation state, determined by measurement of both phagocytic index and beta-glucuronidase content, was found to be markedly higher in tumor-associated macrophages than in their peritoneal counterparts and it was, in addition, independent of tumor progression. The percentage of tumor-associated macrophages, which were detected on the basis of Fc receptor expression, remained constant in the growing neoplasm, at approximately 23% of total cell population. None of these parameters were affected by inoculation with an immunopotentiating dose of heat-killed Candida albicans which, on the other hand, seemed not to alter the course of the tumor. These data suggest that within the tumor microenvironment macrophages would somehow be maintained at a constant proportion and at a highly activated state, while outside the tumor they would be at a lower activation level. Our results also suggest that TAM would not possess antitumor activity in vivo, although we have found this activity in vitro.

Use of a carbon dioxide laser for surgical management of cutaneous masses in horses: 65 cases (1993-2004)

NASA Astrophysics Data System (ADS)

Hawkins, Jan F.; McCauley, Charles T.

2005-04-01

The purpose of this study was to evaluate the outcome of horses treated for cutaneous masses with the carbon dioxide (CO2) laser. The records of 65 horses were examined. Surgery was performed under general anesthesia or standing under sedation and local anesthesia. Excision was performed freehand using a focused beam with power settings ranging from 10 to 32 Watts in a continuous mode. Following en bloc removal of masses the subcutaneous tissue and wound margins were photovaporized using a defocused beam. Follow-up information was obtained via telephone interview with owners or referring veterinarians Cutaneous masses were divided into three groups: sarcoid (29), neoplasia including squamous cell carcinoma (15), melanoma (6), schwanoma (2), fibroma (1), and fibrosarcoma (1), and non-neoplastic masses (11). Mass reoccurrence developed in 8 of 29 (28%) sarcoids and 4 of 14 (29%) squamous cell carcinoma. No reoccurrence was reported for horses diagnosed with melanoma, schwanoma, fibrosarcoma, fibroma, or any of the non-neoplastic masses. Sixty of 63 owners (95%) reported that they were satisfied with the outcome of the procedure. This study demonstrates that the CO2 laser is an effective means of treating cutaneous masses in horses.

Local immunotherapy of spontaneous feline fibrosarcomas using recombinant poxviruses expressing interleukin 2 (IL2).

PubMed

Jourdier, T-M; Moste, C; Bonnet, M-C; Delisle, F; Tafani, J-P; Devauchelle, P; Tartaglia, J; Moingeon, P

2003-12-01

We tested the canarypox virus vector ALVAC and the genetically attenuated vaccinia virus vector NYVAC as vehicles for achieving local immunomodulation in domestic animals bearing spontaneous tumours. Following intratumoral administration of ALVAC-, or NYVAC-luciferase in dogs with melanoma, it was demonstrated that viral recombinants remained localized along the needle track, with no virus detectable in the periphery of the tumour. Given these distribution characteristics and their well-documented safety profile, ALVAC- or NYVAC-based recombinants expressing feline or human IL2, respectively, were administered to domestic cats, in order to prevent the recurrence of spontaneous fibrosarcomas. In the absence of immunotherapy, tumour recurrence was observed in 61% of animals within a 12-month follow-up period after treatment with surgery and iridium-based radiotherapy. In contrast, only 39 and 28% of cats receiving either NYVAC-human IL2 or ALVAC-feline IL2, respectively, exhibited tumour recurrences. Based on such results, and in the context of ongoing clinical studies conducted in humans, we discuss the utilization of ALVAC- or NYVAC-based recombinants as viable therapeutic modalities for local immunotherapy or therapeutic vaccination against cancer, both in humans and companion animals.

Gene therapy of spontaneous canine melanoma and feline fibrosarcoma by intratumoral administration of histoincompatible cells expressing human interleukin-2.

PubMed

Quintin-Colonna, F; Devauchelle, P; Fradelizi, D; Mourot, B; Faure, T; Kourilsky, P; Roth, C; Mehtali, M

1996-12-01

The production of human interleukin-2 (hIL-2) local to the tumor site by engineered histoincompatible cells has been shown in various murine models to promote a strong immune response leading to tumor growth inhibition or rejection. To assess whether this strategy would be similarly applicable for treatment of primary neoplastic cells, two naturally occurring tumors were used as preclinical models; the highly metastatic melanoma of the dog and the low metastatic fibrosarcoma of the cat. We demonstrate that both cats and dogs when treated by tumor surgery, radiotherapy and repeated local injections of xenogeneic Vero cells secreting high levels of hIL-2 relapse less frequently and survive longer than control animals treated by surgery and radiotherapy alone. Local secretion of hIL-2 by the xenogeneic cells is shown to be necessary for the induction of an optimal antitumor effect. Moreover, the safety of the procedure was demonstrated in both animal models and through extensive toxicological analysis performed in rats. These results confirm for the first time to our knowledge the safety and therapeutic potential of a gene transfer strategy in animals with spontaneous metastatic and nonmetastatic tumors.

Pycnogenol (PYC) induces apoptosis in human fibrosarcoma (HFS) cells under metal-mediated oxidative stress.

PubMed

Park, Yeon Sun; Kim, Young Gon

2011-01-01

Pycnogenol (PYC), polyphenolic compounds with antioxidant activity, acted as a prooxidant. PYC caused oxidative stress in human fibrosarcoma cells (HFS) when administered following pretreatment with iron chloride. The generated reactive oxygen species (ROS) caused the formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in DNA and resulted in more apoptosis in HFS cells than in the human fibroblastoma (HFB) cells. DNA damage and cellular viability at different PYC concentrations were closely consistent with cell growth, high performance liquid chromatography (HPLC), Enzyme Linked Immunosorbent Assay (ELISA) and assays of two major antioxidant enzymes, superoxide dismutase (SOD) and catalase. Although the presence of PYC induced total SOD and catalase activities under oxidative stress in dose dependent fashion, more apoptotic cells were induced in HFS cells with increased [8-OHdG] than in HFB cells. The results suggest that PYC selectively induced cell death in HFS cells. This further confirmed that PYC-induced apoptosis is mediated primarily through the activation of caspase-3 apoptotic marker in HFS cells but not in HFB cells. We conclude that PYC would behave as either antioxidant or prooxidant dependant upon the cellular types.

Effect of Agmatine Sulfate on Modulation of Matrix Metalloproteinases via PI3K/Akt-1 in HT1080 Cells.

PubMed

Kim, Hyejeong; Kim, Moon-Moo

2017-11-01

The purpose of this study was to investigate the mechanism by which agmatine sulfate induces an anti-metastatic effect in human HT1080 fibrosarcoma cells, by affecting matrix metalloproteinases (MMPs). For the experiments, we used a non-toxic concentration of agmatine, below 512 μM, that was determined using an MTT assay. The effect of agmatine sulfate on metastasis was gelatin zymography, western blot, immunofluorescence staining and cell invasion assay. Agmatine sulfate inhibited MMP-2 activity stimulated by phenazine methosulfate (PMS). Furthermore, the expression level of MMP-2 stimulated by PMS, was decreased, but the expression level of TIMP-1 was increased in the presence of agmatine sulfate. Moreover, it was observed that the expression levels of ERK and p38 were increased, but those of PI3K and Akt-1 associated with the modulation of MMP-2 were decreased in this study. Furthermore, agmatine sulfate decreased the invasion level of human fibrosarcoma cells stimulated by VEGF. These results suggest that agmatine sulfate could inhibit metastasis through inhibition of MMP-2 via the PI3K/Akt-1 signaling pathway. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

TFG-MET fusion in an infantile spindle cell sarcoma with neural features.

PubMed

Flucke, Uta; van Noesel, Max M; Wijnen, Marc; Zhang, Lei; Chen, Chun-Liang; Sung, Yun-Shao; Antonescu, Cristina R

2017-09-01

An increasing number of congenital and infantile sarcomas displaying a primitive, monomorphic spindle cell phenotype have been characterized to harbor recurrent gene fusions, including infantile fibrosarcoma and congenital spindle cell rhabdomyosarcoma. Here, we report an unusual spindle cell sarcoma presenting as a large and infiltrative pelvic soft tissue mass in a 4-month-old girl, which revealed a novel TFG-MET gene fusion by whole transcriptome RNA sequencing. The tumor resembled the morphology of an infantile fibrosarcoma with both fascicular and patternless growth, however, it expressed strong S100 protein immunoreactivity, while lacking SOX10 staining and retaining H3K27me3 expression. Although this immunoprofile suggested partial neural/neuroectodermal differentiation, overall features were unusual and did not fit into any known tumor types (cellular schwannoma, MPNST), raising the possibility of a novel pathologic entity. The TFG-MET gene fusion expands the genetic spectrum implicated in the pathogenesis of congenital spindle cell sarcomas, with yet another example of kinase oncogenic activation through chromosomal translocation. The discovery of this new fusion is significant since the resulting MET activation can potentially be inhibited by targeted therapy, as MET inhibitors are presently available in clinical trials. © 2017 Wiley Periodicals, Inc.

Preparation and Biodistribution Studies of a Radiogallium-Acetylacetonate Bis (Thiosemicarbazone) Complex in Tumor-Bearing Rodents

PubMed Central

Jalilian, Amir Reza; Yousefnia, Hassan; Shafaii, Kamaleddin; Novinrouz, Aytak; Rajamand, Amir Abbas

2012-01-01

Various radiometal complexes have been developed for tumor imaging, especially Ga-68 tracer. In the present study, the development of a radiogallium bis-thiosemicarbazone complex has been reported. [67Ga] acetylacetonate bis(thiosemicarbazone) complex ([67Ga] AATS) was prepared starting [67Ga]Gallium acetate and freshly prepared acetylacetonate bis (thiosemicarbazone) (AATS) in 30 min at 90°C. The partition co-efficient and the stability of the tracer were determined in final solution (25°C) and the presence of human serum (37°C) up to 24 h. The biodistribution of the labeled compound in wild-type and fibrosarcoma-bearing rodents were determined up to 72 h. The radiolabled Ga complex was prepared in high radiochemical purity (> 97%, HPLC) followed by initial biodistribution data with the significant tumor accumulation of the tracer in 2 h which is far higher than free Ga-67 cation while the compound wash-out is significantly faster. Above-mentioned pharmacokinetic properties suggest an interesting radiogallium complex while prepared by the PET Ga radioisotope, 68Ga, in accordance with the physical half life, for use in fibrosarcoma tumors, and possibly other malignancies. PMID:24250475

Effect of axial ligation and delivery system on the tumour-localising and -photosensitising properties of Ge(IV)-octabutoxy-phthalocyanines.

PubMed Central

Soncin, M.; Polo, L.; Reddi, E.; Jori, G.; Kenney, M. E.; Cheng, G.; Rodgers, M. A.

1995-01-01

Four Ge(IV)-octabutoxy-phthalocyanines (GePcs) bearing two alkyl-type axial ligands were assayed for their pharmacokinetic properties and phototherapeutic efficiency in Balb/c mice bearing an intramuscularly transplanted MS-2 fibrosarcoma. The GePcs were i.v. injected at a dose of 0.35 mumol kg-1 body weight after incorporation into either Cremophor emulsions or small unilamellar liposomes of dipalmitoyl-phosphatidylcholine (DPPC). Both the nature of the delivery system and the chemical structure of the phthalocyanine were found to affect the behaviour of the GePcs in vivo. Thus, Cremophor-administered GePcs invariably yielded a more prolonged serum retention and a larger association with low-density lipoproteins (LDLs) as compared with the corresponding liposome-delivered phthalocyanines. This led to a greater efficiency and selectivity of tumour targeting. These effects were more pronounced for those GePcs having relatively long alkyl chains (hexyl to decyl) in the axial ligands. Maximal tumour accumulation (0.67 nmol per g of tissue) was found for Ge-Pc(hexyl)2 at 24 h after injection. Consistently, the Ge-Pc(hexyl)2, administered via Cremophor, showed the highest phototherapeutic activity towards MS-2 fibrosarcoma. PMID:7710936

Phage Display Breast Carcinoma cDNA Libraries: Isolation of Clones Which Specifically Bind to Membrane Glycoproteins, Mucins, and Endothelial Cell Surface

DTIC Science & Technology

1999-07-01

nutrients and waste and UV 2237 fibrosarcoma sublines (17). Expression of elimination, cell surfaces are also important for the galectin-1, another member of...10B capsid protein. Therefore, this GAG CGG AAA ATG GCA GAC AAT TTT TCG CTC CAT ... vector was chosen to assess the feasibility of phage met Ala Asp

Targeting of Prostate Cancer with Hyaluronan-Binding Proteins

DTIC Science & Technology

2005-06-01

16). Briefly, bovine nasal cartilage (Pel-Freez, Rogers, AR) was shredded with a Sure-Form blade (Stanley). extracted overnight with 4 M guanidine... nasal cartilage by affinity chromatography on hyaluronan- E Sepharose. As shown in Fig. 1, Metastatin consisted of two molecular C 40 factions as...biotinylated 490 pg/ml.) was isolated from the medium of rat fibrosarcoma cells grown tachvplesin (Fig. IB). However, this interaction was

Synovial sarcoma of the jaw in a dog.

PubMed

Griffith, J W; Frey, R A; Sharkey, F E

1987-05-01

A case of synovial sarcoma of the jaw with pulmonary metastasis is described in a dog. It appears to be a rare or underdiagnosed neoplasm in animals and not previously reported in the jaw. Its diagnostic microscopic features are the biphasic cellular pattern and cleft formations. It may otherwise resemble haemangiopericytoma, malignant fibrous histiocytoma, reticulum cell sarcoma, fibrosarcoma, or giant-cell tumour of soft tissue.

[Dedifferentiated chondrosarcoma: radiologic-pathologic correlation].

PubMed

Bierry, G; Feydy, A; Larousserie, F; Pluot, E; Guerini, H; Campagna, R; Dufau-Andreu, C; Anract, P; Babinet, A; Dietemann, J L; Chevrot, A; Drapé, J L

2010-03-01

Dedifferentiated chondrosarcomas are highly malignant tumors characterized by conventional low-grade chondrosarcoma with abrupt transition to foci that have dedifferentiated into a higher-grade noncartilaginous more aggressive sarcoma. The dedifferentiated component, an osteosarcoma or fibrosarcoma, determines the prognosis. Its identification is key for management. A diagnosis of dedifferentiated chondrosarcoma should be suggested by the presence of "tumoral dimorphism" with cartilaginous component and aggressive lytic component invading adjacent soft tissues.

Malignant odontogenic tumors. A retrospective and collaborative study of seven cases.

PubMed

Mosqueda Taylor, Adalberto; Meneses García, Abelardo; Ruíz Godoy Rivera, Luz María; Suárez Roa, María de Lourdes; Luna Ortiz, Kuauhyama

2003-01-01

The frequency, clinico-pathologic features and outcome of malignant odontogenic tumors diagnosed according to the current WHO classification in three pathology services in Mexico City are presented. There were seven cases (5 male and 2 female patients), which represent less than 4% of all odontogenic tumors diagnosed in these services. There were six odontogenic carcinomas (two malignant ameloblastomas, two clear cell odontogenic carcinomas, one primary intraosseous carcinoma and one carcinoma arising in an odontogenic cyst) and one ameloblastic fibrosarcoma. Age ranged from 25 to 72 years (mean: 43.8). Clear cell odontogenic carcinomas occurred in the canine-premolar region, one in the maxilla and one in the mandible (one ia a man and one in a woman), while the remaining lesions affected the posterior region of the mandible, with a male predominance (4:1), which agrees with previously reported cases. Surgical resection was the treatment employed in all carcinomas, while the ameloblastic fibrosarcoma was treated with chemotherapy due to its large extension, but without favorable response. The patient with primary intraosseous carcinoma had submaxillary and cervical metastases and the neoplasm was the cause of death. In spite of their extremely low frequency, malignant odontogenic tumors are an important cause of extensive surgical procedures in the oral and maxillofacial region.

Radiation induction of cancer of the skin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fry, R.J.M.; Storer, J.B.; Burns, F.J.

1985-01-01

The induction of epidermal tumors was studied using exposures to 25 kV x-rays with or without subsequent exposures to 12-0-tetradeconyl phorbol-13 acetate (TPA) or ultraviolet radiation (uvr) 280-400 nm. Fractionation regimens and total exposure up to 4000R produced no squamous cell carcinomas. When these regimes were followed by TPA an incidence of about 80% was obtained, and incidence of 60% when uvr exposures followed the x-irradiation. A dose-dependent increase in fibrosarcomas was found when x-irradiation was followed by 24 weeks of topical treatment with TPA. These results support the contention that uvr can enhance the expression of cells initiated bymore » x-rays. The experimental evidence is compared with the data from the tinea capitis patients treated with x-rays. In C3HF/He male mice exposed to 50, 100, 150 and 200 rads /sup 137/Cs gamma rays the induction rate for fibrosarcomas was 2.9 x 10/sup -4/ per cGy/per mouse. This result compares with 2.5 x 10/sup -6/ transformations per surviving cell per cGy with 10T1/2 cells that are fibroblasts derived from C3H mice. 16 refs., 1 fig., 1 tab.« less

Hyaluronidase and Collagenase Increase the Transfection Efficiency of Gene Electrotransfer in Various Murine Tumors

PubMed Central

Golzio, Muriel; Sersa, Gregor; Escoffre, Jean-Michel; Coer, Andrej; Vidic, Suzana; Teissie, Justin

2012-01-01

Abstract One of the applications of electroporation/electropulsation in biomedicine is gene electrotransfer, the wider use of which is hindered by low transfection efficiency in vivo compared with viral vectors. The aim of our study was to determine whether modulation of the extracellular matrix in solid tumors, using collagenase and hyaluronidase, could increase the transfection efficiency of gene electrotransfer in histologically different solid subcutaneous tumors in mice. Tumors were treated with enzymes before electrotransfer of plasmid DNA encoding either green fluorescent protein or luciferase. Transfection efficiency was determined 3, 9, and 15 days posttransfection. We demonstrated that pretreatment of tumors with a combination of enzymes significantly increased the transfection efficiency of electrotransfer in tumors with a high extracellular matrix area (LPB fibrosarcoma). In tumors with a smaller extracellular matrix area and less organized collagen lattice, the increase was not so pronounced (SA-1 fibrosarcoma and EAT carcinoma), whereas in B16 melanoma, in which only traces of collagen are present, pretreatment of tumors with hyaluronidase alone was more efficient than pretreatment with both enzymes. In conclusion, our results suggest that modification of the extracellular matrix could improve distribution of plasmid DNA in solid subcutaneous tumors, demonstrated by an increase in transfection efficiency, and thus have important clinical implications for electrogene therapy. PMID:21797718

Presence of closely spaced protein thiols on the surface of mammalian cells.

PubMed Central

Donoghue, N.; Yam, P. T.; Jiang, X. M.; Hogg, P. J.

2000-01-01

It has been proposed that certain cell-surface proteins undergo redox reactions, that is, transfer of hydrogens and electrons between closely spaced cysteine thiols that can lead to reduction, formation, or interchange of disulfide bonds. This concept was tested using a membrane-impermeable trivalent arsenical to identify closely spaced thiols in cell-surface proteins. We attached the trivalent arsenical, phenylarsenoxide, to the thiol of reduced glutathione to produce 4-(N-(S-glutathionylacetyl)amino)phenylarsenoxide (GSAO). GSAO bound tightly to synthetic, peptide, and protein dithiols like thioredoxin, but not to monothiols. To identify cell-surface proteins that contain closely spaced thiols, we attached a biotin moiety through a spacer arm to the primary amino group of the gamma-glutamyl residue of GSAO (GSAO-B). Incorporation of GSAO-B into proteins was assessed by measuring the biotin using streptavidin-peroxidase. Up to 12 distinct proteins were labeled with GSAO-B on the surface of endothelial and fibrosarcoma cells. The pattern of labeled proteins differed between the different cell types. Protein disulfide isomerase was one of the proteins on the endothelial and fibrosarcoma cell surface that incorporated GSAO-B. These findings demonstrate that the cell-surface environment can support the existence of closely spaced protein thiols and suggest that at least some of these thiols are redox active. PMID:11206065

Single dose x irradiation and concomitant hyperthermia on a murine fibroscarcoma. [Sensitizing effects of hyperthermia on tumors in mice subjected to local radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hahn, E.W.; Alfieri, A.A.; Kim, J.H.

1978-12-01

The objectives of this study were to quantitate the effects of local tumor hyperthermia (LTH) and concomitant x irradiation (RAD) on a moderately radioresistant murine fibrosarcoma in situ. Comparisons were made to the combined treatment response on the Ridgway osteogenic sarcoma, a radiosensitive tumor previously used in this laboratory and to establish the Meth-A fibrosarcoma as a model system for combined modality studies. 1.0 cm/sup 3/ tumors were exposed to single doses of RAD ranging from 0.5 to 3.8 krad alone or 0.5 to 2.3 krad in combination with LTH (water bath at 43.1 +- .05 C for 20 minutes)more » applied immediately postirradiation. LTH significantly enhanced the action of radiation as measured by tumor volume analysis, mean survival time and cures. The ratio of radiation doses vs. RAD + LTH required to produce an equivalent response ranged from 1.4 to 2.5 depending upon the endpoints evaluated. These findings are consistent with single dose studies on the radiosensitive Ridgway osteogenic sarcoma and suggest that the tumoricidal effectiveness of combination radiation and hyperthermia cannot be predicted on the basis of the radiation alone responsiveness of tumor.« less

Enhanced Expression of Interferon-γ-Induced Antigen-Processing Machinery Components in a Spontaneously Occurring Cancer1

PubMed Central

Cerruti, Fulvia; Martano, Marina; Petterino, Claudio; Bollo, Enrico; Morello, Emanuela; Bruno, Renato; Buracco, Paolo; Cascio, Paolo

2007-01-01

In human tumors, changes in the surface expression and/or function of major histocompatibility complex (MHC) class I antigens are frequently found and may provide malignant cells with a mechanism to escape control of the immune system. This altered human lymphocyte antigen (HLA) class I phenotype can be caused by either structural alterations or dysregulation of genes encoding subunits of HLA class I antigens and/or components of the MHC class I antigen-processing machinery (APM). Herein we analyze the expression of several proteins involved in the generation of MHC class I epitopes in feline injection site sarcoma, a spontaneously occurring tumor in cats that is an informativemodel for the study of tumor biology in other species, including humans. Eighteen surgically removed primary fibrosarcoma lesions were analyzed, and an enhanced expression of two catalytic subunits of immunoproteasomes, PA28 and leucine aminopeptidase, was found in tumors compared to matched normal tissues. As a functional counterpart of these changes in protein levels, proteasomal activities were increased in tissue extracts from fibrosarcomas. Taken together, these results suggest that alterations in the APM system may account for reduced processing of selected tumor antigens and may potentially provide neoplastic fibroblasts with a mechanism for escape from T-cell recognition and destruction. PMID:18030364

Enhanced expression of interferon-gamma-induced antigen-processing machinery components in a spontaneously occurring cancer.

PubMed

Cerruti, Fulvia; Martano, Marina; Petterino, Claudio; Bollo, Enrico; Morello, Emanuela; Bruno, Renato; Buracco, Paolo; Cascio, Paolo

2007-11-01

In human tumors, changes in the surface expression and/or function of major histocompatibility complex (MHC) class I antigens are frequently found and may provide malignant cells with a mechanism to escape control of the immune system. This altered human lymphocyte antigen (HLA) class I phenotype can be caused by either structural alterations or dysregulation of genes encoding subunits of HLA class I antigens and/or components of the MHC class I antigen-processing machinery (APM). Herein we analyze the expression of several proteins involved in the generation of MHC class I epitopes in feline injection site sarcoma, a spontaneously occurring tumor in cats that is an informative model for the study of tumor biology in other species, including humans. Eighteen surgically removed primary fibrosarcoma lesions were analyzed, and an enhanced expression of two catalytic subunits of immunoproteasomes, PA28 and leucine aminopeptidase, was found in tumors compared to matched normal tissues. As a functional counterpart of these changes in protein levels, proteasomal activities were increased in tissue extracts from fibrosarcomas. Taken together, these results suggest that alterations in the APM system may account for reduced processing of selected tumor antigens and may potentially provide neoplastic fibroblasts with a mechanism for escape from T-cell recognition and destruction.

Use of a spiral rectal diaphragm technique to control anal sphincter incontinence in a cat.

PubMed

Pavletic, Michael; Mahn, Matt; Duddy, Jean

2012-09-15

A 10-year-old castrated male domestic shorthair cat was examined for a mass involving the right anal sac region. The mass was diagnosed as a fibrosarcoma, and resulted in progressive tenesmus, requiring repeated resection. Surgical removal of the fibrosarcoma was performed on 4 occasions, including complete resection of the anal sphincter muscles and portions of the rectum. A perineal urethrostomy was required during the third surgical procedure secondary to tumor invasion of the preputial tissues. To reduce involuntary loss of feces, the remaining rectal wall was rotated approximately 225° prior to surgical closure during the second, third, and fourth surgical procedures. This procedure created a natural spiral diaphragm within the rectal lumen. The elastic spiral barrier reduced inadvertent fecal loss and facilitated fecal distention of the terminal portion of the colon, allowing the patient to anticipate the impending passage of feces and to use the litter tray on a daily basis. With complete loss of the terminal portion of the rectum and anal sphincter muscles, spiraling the rectum created a deformable threshold barrier to reduce excessive loss of stool secondary to fecal incontinence. On the basis of the positive outcome in this patient, this novel technique may be a useful option to consider for the treatment of cats with loss of anal sphincter function.

Type I collagen gel protects murine fibrosarcoma L929 cells from TNFα-induced cell death

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Hong-Ju; He, Wen-Qi; Chen, Ling

Murine fibrosarcoma L929 cells have been used to test efficacy of proinflammatory cytokine TNFα. In the present study, we reported on protective effect of type I collagen gel used as L929 cell culture. L929 cell grew and proliferated well on collagen gel. However, the L929 cells exhibited cobblestone-like morphology which was much different from the spread fusiform shape when cultured on conventional cell dishes as well as the cells tended to aggregate. On conventional cell culture dishes, the cells treated with TNFα became round in shape and eventually died in a necroptotic manner. The cells cultured on collagen gel, however,more » were completely unaffected. TNFα treatment was reported to induce autophagy in L929 cells on the plastic dish, and therefore we investigated the effect of collagen gel on induction of autophagy. The results indicated that autophagy induced by TNFα treatment was much reduced when the cells were cultured on collagen gel. In conclusion, type I collagen gel protected L929 cell from TNFα-induced cell death. - Highlights: • Collagen gel culture changed the morphology of L929 cells. • L929 cell cultured on collagen gel were resistant to TNFα-induced cell death. • Collagen gel culture inhibited TNFα-induced autophagy in L929 cells.« less

Differential effects of trichostatin A on gelatinase A expression in 3T3 fibroblasts and HT-1080 fibrosarcoma cells: implications for use of TSA in cancer therapy.

PubMed

Ailenberg, Menachem; Silverman, Mel

2003-03-07

Trichostatin A (TSA) is a histone deacetylase (HDAC) inhibitor with potential in cancer therapeutics. In a recent communication, we demonstrated that TSA is a selective, potent inhibitor of gelatinase A in 3T3 fibroblasts. In the present study, we extend these observations and examine the effects of TSA in 3T3 fibroblasts compared to HT-1080 fibrosarcoma cells with respect to gelatinase A expression, cell viability, and apoptosis. We find that while expression of gelatinase A in 3T3 fibroblasts is exquisitely sensitive to inhibition by TSA, expression of this enzyme in HT-1080 cells is minimally affected by this compound. Moreover, we show that TSA is pro-apoptotic in HT-1080 cells, but is anti-apoptotic in 3T3 cells. We propose a two-pronged model for the therapeutic action of TSA. On the one hand TSA selectively decreases cancer cell viability, while enhancing the viability of stromal cells. On the other hand, by selectively decreasing gelatinase A expression in stromal but not cancer cells, TSA acts to control metastatic potential by reducing the ability of metastatic cells to recruit stromal cells to secrete gelatinase A.

USSR and Eastern Europe Scientific Abstracts Biomedical and Behavioral Sciences No. 78.

DTIC Science & Technology

1977-09-02

references 9: 7 Russian, 2 Western. USSR UDC 612.215.014.2.014.426 MORPHOLOGICAL AND HISTOLOGICAL CHANGES IN NASAL MUCOSA DUE TO THE ACTION OF UHF...Nose and Throat Diseases and of Human Anatomy, Zaporozhe Medical Institute [Abstract] It has been established that the changes occurring in nasal ...varies for different plastics. Histologically, a large part of the developing tumor is made up of fibrosarcomas ; however, also seen are osteosarcomas

Respirator Qualitative/Quantitative Fit Test Method Analysis

DTIC Science & Technology

1980-08-01

carefully fitted to sample the atmosphere in the oral/ nasal or visual cavity. Leakage is expressed as a ratio of the ambient challenge atmosphere...8, 10, 40, 205, 274). While cer- Lain counercial polymer films have reportedly caused fibrosarcomas and other tumors in rats, this has been attributed... nasal passages (Portland cement dust), or cause injury to the skin or mucous membranes by chemical or mechanical action per se or by the rigorous skin

Island palatal mucoperiosteal flap for repair of oronasal fistula in a dog.

PubMed

Smith, M M

2001-09-01

A two-year-old neutered/male mixed-breed dog had received partial maxillectomy for fibrosarcoma. An oronasal fistula occurred as a complication of the surgical procedure. An island palatal mucoperiosteal flap was developed and rotated to repair the oronasal fistula. Acute (1-month) and long-term (8-months) follow-up indicated appropriate healing of the transposed island palatal mucoperiosteal flap with resolution of clinical signs indicative of oronasal fistula.

Prevention of 3-methylcholanthrene-induced fibrosarcomas in rats pre-inoculated with endogenous rat retrovirus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fish, D.C.; Demarais, J.T.; Djurickovic, D.B.

1981-04-01

Weanling Fischer 344 rats received a single intraperitoneal injection of a 1000-fold concentrated preparation of endogenous nontransforming rat retrovirus. Ten days later, the rats were each given a single subcutaneous injection of 3-methylcholanthrene. The rats inoculated with the endogenous rat retrovirus were significantly protected against the development of cancer, whereas uninoculated rats and rats given one of several murine tetroviruses or baboon retrovirus were not protected.

Environmentally Induced Gene Silencing in Breast Cancer

DTIC Science & Technology

2007-07-01

fibrosarcoma cell line (HTD114), and a human breast cancer cell line (MCF7). The MLH1 promoter was only tested in the MCG7 cells. The control TRE-Luc...TRE- Luc MLH1 - Luc step in silencing is quite unstable. Nonetheless, cells that exhibit stable silencing of the HPRT construct can arise in...mechanism (i.e., gene repression). Finally, during the last year we have isolated or acquired functional promoters for the BRCA-1, MLH1 , and E

Gemcitabine Hydrochloride With or Without Pazopanib Hydrochloride in Treating Patients With Refractory Soft Tissue Sarcoma

ClinicalTrials.gov

2017-11-01

Adult Alveolar Soft Part Sarcoma; Adult Angiosarcoma; Adult Desmoplastic Small Round Cell Tumor; Adult Epithelioid Hemangioendothelioma; Adult Epithelioid Sarcoma; Adult Extraskeletal Myxoid Chondrosarcoma; Adult Extraskeletal Osteosarcoma; Adult Fibrosarcoma; Adult Leiomyosarcoma; Adult Liposarcoma; Adult Malignant Mesenchymoma; Adult Malignant Peripheral Nerve Sheath Tumor; Adult Rhabdomyosarcoma; Adult Synovial Sarcoma; Adult Undifferentiated Pleomorphic Sarcoma; Malignant Adult Hemangiopericytoma; Recurrent Adult Soft Tissue Sarcoma; Stage III Adult Soft Tissue Sarcoma; Stage IV Adult Soft Tissue Sarcoma

Depsipeptide (Romidepsin) in Treating Patients With Metastatic or Unresectable Soft Tissue Sarcoma

ClinicalTrials.gov

2017-05-18

Adult Alveolar Soft-part Sarcoma; Adult Angiosarcoma; Adult Epithelioid Sarcoma; Adult Extraskeletal Chondrosarcoma; Adult Extraskeletal Osteosarcoma; Adult Fibrosarcoma; Adult Leiomyosarcoma; Adult Liposarcoma; Adult Malignant Fibrous Histiocytoma; Adult Malignant Hemangiopericytoma; Adult Malignant Mesenchymoma; Adult Neurofibrosarcoma; Adult Rhabdomyosarcoma; Adult Synovial Sarcoma; Gastrointestinal Stromal Tumor; Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Adult Soft Tissue Sarcoma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Stage III Adult Soft Tissue Sarcoma; Stage IV Adult Soft Tissue Sarcoma

Chronic Mammalian Toxicological Effects of LAP Wastewater.

DTIC Science & Technology

1983-06-01

humped back, cyanosis, hyperactivity, ataxia, nasal exudate, chromodacryorrhea, and opisthotonos. All rats receiving LAP had red urine approximately 1...treatment, this animal had a humped appearance and was emaciated; a bloody nasal exudate was also noted. Necropsy revealed marked emphysema and moderate...16 17 9 Pigmentation, focal 0 0 1 0 0 2 Fibrosarcoma , metastatic 1 0 0 2 0 0 Neurilemoma 0 1 0 0 2 0 Duodenum Mineralization, focal 0 0 1 0 0 2

Is cancer a pure growth curve or does it follow a kinetics of dynamical structural transformation?

PubMed

González, Maraelys Morales; Joa, Javier Antonio González; Cabrales, Luis Enrique Bergues; Pupo, Ana Elisa Bergues; Schneider, Baruch; Kondakci, Suleyman; Ciria, Héctor Manuel Camué; Reyes, Juan Bory; Jarque, Manuel Verdecia; Mateus, Miguel Angel O'Farril; González, Tamara Rubio; Brooks, Soraida Candida Acosta; Cáceres, José Luis Hernández; González, Gustavo Victoriano Sierra

2017-03-07

Unperturbed tumor growth kinetics is one of the more studied cancer topics; however, it is poorly understood. Mathematical modeling is a useful tool to elucidate new mechanisms involved in tumor growth kinetics, which can be relevant to understand cancer genesis and select the most suitable treatment. The classical Kolmogorov-Johnson-Mehl-Avrami as well as the modified Kolmogorov-Johnson-Mehl-Avrami models to describe unperturbed fibrosarcoma Sa-37 tumor growth are used and compared with the Gompertz modified and Logistic models. Viable tumor cells (1×10 5 ) are inoculated to 28 BALB/c male mice. Modified Gompertz, Logistic, Kolmogorov-Johnson-Mehl-Avrami classical and modified Kolmogorov-Johnson-Mehl-Avrami models fit well to the experimental data and agree with one another. A jump in the time behaviors of the instantaneous slopes of classical and modified Kolmogorov-Johnson-Mehl-Avrami models and high values of these instantaneous slopes at very early stages of tumor growth kinetics are observed. The modified Kolmogorov-Johnson-Mehl-Avrami equation can be used to describe unperturbed fibrosarcoma Sa-37 tumor growth. It reveals that diffusion-controlled nucleation/growth and impingement mechanisms are involved in tumor growth kinetics. On the other hand, tumor development kinetics reveals dynamical structural transformations rather than a pure growth curve. Tumor fractal property prevails during entire TGK.

Comparative uptake of ¹⁸F-FEN-DPAZn2, ¹⁸F-FECH, ¹⁸F-fluoride, and ¹⁸F-FDG in fibrosarcoma and aseptic inflammation.

PubMed

Liang, Xiang; Tang, Ganghua; Wang, Hongliang; Hu, Kongzhen; Tang, Xiaolan; Nie, Dahong; Sun, Ting; Huang, Tingting

2014-08-01

The aim of this study is to evaluate uptake of 2-(18)F-fluoroethyl-bis(zinc(II)-dipicolylamine) ((18)F-FEN-DPAZn2) as a promising cell death imaging agent, a choline analog (18)F-fluoroethylcholine ((18)F-FECH), (18)F-fluoride as a bone imaging agent, and a glucose analog 2-(18)F-fluoro-2-deoxy-d-glucose ((18)F-FDG) in the combined S180 fibrosarcoma and turpentine-induced inflammation mice models. The results showed that (18)F-FDG had the highest tumor-to-blood uptake ratio and tumor-to-muscle ratio, and high inflammation-to-blood ratio and inflammation-to-muscle ratio. (18)F -FECH showed moderate tumor-to-blood ratio and tumor-to-muscle ratio, and low inflammation-to-blood ratio and inflammation-to-muscle ratio. However, accumulation of (18)F FEN-DPAZn2 in tumor was similar to that in normal muscle. Also, (18)F-FEN-DPAZn2 and (18)F-fluoride exhibited the best selectivity to inflammation. (18)F-FECH positron emission tomography (PET) imaging demonstrates some advantages over (18)F-FDG PET for the differentiation of tumor from inflammation. (18)F FEN-DPAZn2 and (18)F-fluoride can be used for PET imaging of aseptic inflammation. Copyright © 2014 Elsevier Ltd. All rights reserved.

LC3-mediated fibronectin mRNA translation induces fibrosarcoma growth by increasing connective tissue growth factor

PubMed Central

Ying, Lihua; Lau, Agatha; Alvira, Cristina M.; West, Robert; Cann, Gordon M.; Zhou, Bin; Kinnear, Caroline; Jan, Eric; Sarnow, Peter; Van de Rijn, Matt; Rabinovitch, Marlene

2009-01-01

Summary Previously, we related fibronectin (Fn1) mRNA translation to an interaction between an AU-rich element in the Fn1 3′ UTR and light chain 3 (LC3) of microtubule-associated proteins 1A and 1B. Since human fibrosarcoma (HT1080) cells produce little fibronectin and LC3, we used these cells to investigate how LC3-mediated Fn1 mRNA translation might alter tumor growth. Transfection of HT1080 cells with LC3 enhanced fibronectin mRNA translation. Using polysome analysis and RNA-binding assays, we show that elevated levels of translation depend on an interaction between a triple arginine motif in LC3 and the AU-rich element in Fn1 mRNA. Wild-type but not mutant LC3 accelerated HT1080 cell growth in culture and when implanted in SCID mice. Comparison of WT LC3 with vector-transfected HT1080 cells revealed increased fibronectin-dependent proliferation, adhesion and invasion. Microarray analysis of genes differentially expressed in WT and vector-transfected control cells indicated enhanced expression of connective tissue growth factor (CTGF). Using siRNA, we show that enhanced expression of CTGF is fibronectin dependent and that LC3-mediated adhesion, invasion and proliferation are CTGF dependent. Expression profiling of soft tissue tumors revealed increased expression of both LC3 and CTGF in some locally invasive tumor types. PMID:19366727

Molecular analysis of the inhibition of interleukin-8 production by dexamethasone in a human fibrosarcoma cell line.

PubMed Central

Mukaida, N; Gussella, G L; Kasahara, T; Ko, Y; Zachariae, C O; Kawai, T; Matsushima, K

1992-01-01

In order to analyse the effects of glucocorticoids on interleukin-8 (IL-8) production more precisely, we examined the effects of dexamethasone on IL-8 production at the molecular level in a human fibrosarcoma cell line, 8387, which IL-1 induces to express IL-8 messenger RNA (mRNA) and to secrete IL-8. Over a wide dose range, dexamethasone inhibited IL-8 production induced by IL-1 alpha stimulation. Northern blotting analysis showed that dexamethasone also inhibited the IL-8 mRNA accumulation in a similar dose-related manner. Nuclear run-off assay revealed that dexamethasone decreased the transcription of the IL-8 gene and the degree of inhibition of transcription correlated well with the inhibition of IL-8 production, suggesting that the action of glucocorticoids is mainly at the transcriptional level. Furthermore, transfection with chloramphenicol acetyl transferase (CAT) expression vectors inserted with the 5'-deleted IL-8 gene demonstrated that the 5'-flanking region which contains the glucocorticoid response element (GRE) was mainly involved in the dexamethasone-induced repression of the IL-8 gene. These data suggest that the inhibition of the IL-8 gene transcription by glucocorticoids occurs through the interaction of the glucocorticoid receptor complex with GRE in the 5'-flanking region of the IL-8 gene. Images Figure 1 Figure 2 Figure 3 PMID:1592440

A case of interscapular fibrosarcoma in a dwarf rabbit (Oryctolagus cuniculus).

PubMed

Petterino, Claudio; Modesto, Paola; Strata, Daniela; Vascellari, Marta; Mutinelli, Franco; Ferrari, Angelo; Ratto, Alessandra

2009-11-01

A 1-year-old, intact, male dwarf rabbit (Oryctolagus cuniculus) was vaccinated against myxomatosis and rabbit viral hemorrhagic disease in February 1999, and a localized reaction appeared in the same anatomic site within a few days. No regression was observed after subcutaneous antibiotic treatment. The rabbit was kept under observation, and the swelling apparently disappeared in 3 months. The owner then decided to avoid any further subcutaneous drug administration. The referring veterinarian examined the animal on July 2006 for the sudden appearance of a nodular, 4.5 cm x 3.5 cm x 2.0 cm, subcutaneous mass located over the interscapular space. Fine-needle aspiration was performed, and a population of neoplastic spindle cells, rare pleomorphic multinucleated cells, and rare leukocytes were observed. The mass was surgically removed, fixed in 10% neutral buffered formalin, and routinely processed for histologic, histochemical, and immunohistochemical diagnostic investigation. The neoplastic tissue exhibited fascicles composed of malignant spindle-shaped cells with elongated to oval hyperchromatic nuclei and scant cytoplasm. Occasional multinucleated cells were also observed. The neoplastic cells were immunoreactive for vimentin but did not stain for smooth muscle actin, desmin, myoglobin, and cytokeratins (AE1/AE3). Moreover, the histochemical stain for aluminum was positive. The diagnosis was fibrosarcoma based on morphologic and immunohistochemical results. The histologic features of this neoplasm were remarkably similar to feline injection-site sarcoma.

Targeting filamin A reduces K-RAS–induced lung adenocarcinomas and endothelial response to tumor growth in mice

PubMed Central

2012-01-01

Background Many human cancer cells express filamin A (FLNA), an actin-binding structural protein that interacts with a diverse set of cell signaling proteins, but little is known about the biological importance of FLNA in tumor development. FLNA is also expressed in endothelial cells, which may be important for tumor angiogenesis. In this study, we defined the impact of targeting Flna in cancer and endothelial cells on the development of tumors in vivo and on the proliferation of fibroblasts in vitro. Methods First, we used a Cre-adenovirus to simultaneously activate the expression of oncogenic K-RAS and inactivate the expression of Flna in the lung and in fibroblasts. Second, we subcutaneously injected mouse fibrosarcoma cells into mice lacking Flna in endothelial cells. Results Knockout of Flna significantly reduced K-RAS–induced lung tumor formation and the proliferation of oncogenic K-RAS–expressing fibroblasts, and attenuated the activation of the downstream signaling molecules ERK and AKT. Genetic deletion of endothelial FLNA in mice did not impact cardiovascular development; however, knockout of Flna in endothelial cells reduced subcutaneous fibrosarcoma growth and vascularity within tumors. Conclusions We conclude that FLNA is important for lung tumor growth and that endothelial Flna impacts local tumor growth. The data shed new light on the biological importance of FLNA and suggest that targeting this protein might be useful in cancer therapeutics. PMID:22857000

Bleomycin/interleukin-12 electrochemogenetherapy for treating naturally occurring spontaneous neoplasms in dogs.

PubMed

Reed, S D; Fulmer, A; Buckholz, J; Zhang, B; Cutrera, J; Shiomitsu, K; Li, S

2010-08-01

On the basis of superior outcomes from electrochemogenetherapy (ECGT) compared with electrochemotherapy in mice, we determined the efficacy of ECGT applied to spontaneous canine neoplasms. Intralesional bleomycin (BLM) and feline interleukin-12 DNA injection combined with translesional electroporation resulted in complete cure of two recurrent World Health Organization stage T(2b)N(0)M(0) oral squamous cell carcinomas (SCCs) and one T(2)N(0)M(0) acanthomatous ameloblastoma. Three remaining dogs, which had no other treatment options, had partial responses to ECGT; one had mandibular T(3b)N(2b)M(1) melanoma with pulmonary and lymph node metastases; one had cubital T(3)N(0)M(1) histiocytic sarcoma with spleen metastases; and one had soft palate T(3)N(0)M(0) fibrosarcoma. The melanoma dog had decrease in the size of the primary tumor before recrudescence and euthanasia. The histiocytic sarcoma dog had resolution of the primary tumor, but was euthanized because of metastases 4 months after the only treatment. The dog with T(3)N(0)M(0) fibrosarcoma had tumor regression with recrudescence. Treatment was associated with minimal side effects and was easy to perform, was associated with repair of bone lysis in cured dogs, improved quality of life for dogs with partial responses and extended overall survival time. ECGT seems to be a safe and resulted in complete responses in SCC and acanthomatous ameloblastoma.

A novel rat fibrosarcoma cell line from transformed bone marrow-derived mesenchymal stem cells with maintained in vitro and in vivo stemness properties.

PubMed

Wang, Meng-Yu; Nestvold, Janne; Rekdal, Øystein; Kvalheim, Gunnar; Fodstad, Øystein

2017-03-15

Increasing evidence suggests a possible relationship between mesenchymal stem cells (MSCs) and sarcoma. MSCs are hypothesized to be the cells initiating sarcomagenesis, and cancer stem cells (CSCs) sharing features of MSCs have been identified in sarcomas. Here, we report on the characteristics of a bone marrow-derived rat mesenchymal stem cell line that spontaneously transformed in long-term culture. The rat transformed mesenchymal stem cells (rTMSCs) produced soft-tissue fibrosarcomas in immunocompromised mice and immunocompetent rats. In vitro, the rTMSCs displayed increased proliferation capacity compared to the untransformed cell line. The transformed MSCs maintained the mesenchymal phenotype by expression of the stem cell marker CD 90 and the lack of hematopoietic and endothelial markers. Cytogenetic analysis detected trisomy 6 in the rTMSCs. Side population (SP) isolation and tumorsphere cultivation of the transformed cells confirmed the presence of CSCs among the rTMSCs. Importantly, the rTMSCs retained their differentiation capacity towards osteogenic and adipogenic lineages. This transformed MSC-based cell line may be valuable in examining the balance in a mixed cell population between cancer stem cell properties and the ability to differentiate to specific non-transformed cell populations. Moreover, it may also be a useful tool to evaluate the efficacy of novel targeted immunotherapies in vivo. Copyright © 2017 Elsevier Inc. All rights reserved.

Gene Regulation by Retinoid Receptors in Human Mammary Epithelial Cells

DTIC Science & Technology

2002-10-01

ceptors for collagen and fibronectin in human fibrosarcoma cells possessing Xia, Y-, S.G. Gil, and W.G. Carter. 1996. Anchorage mediated by integrin...simultaneously block all TdT terminal deoxynucleotidyl transferase pRB retinoblastoma protein wild-type RAR isoforms (-o, -P, and -- ) (Damm et CAT ...P0 pM treated with 0, 0,1, 1.0, or 10 jIM ATRA for 24 hours and cell lysates were assayed for CAT reporter activity. pCMV-GH was used as a transfection

Air Force Health Study. An Epidemiologic Investigation of Health Effects in Air Force Personnel Following Exposure to Herbicides. Volume 2

DTIC Science & Technology

1991-03-01

association of nasal and nasopharyngeal cancer to chlorophenol exposure (risk ratio, 6.7) was also detected (30), but other specifically focused...published) Selected Cancers Study (SCS) of the3 U.S. CDC focused more specifically on the incidence in Vietnam veterans of the NTIL, STS. HD, nasal ...Comparison had verified STS (fibrous histiocytoma and fibrosarcoma , respectively). The Ranch Hand was not part of the 1987 study because he died; the

Bibliography of Scientific Publications 1975-1993,

DTIC Science & Technology

1994-03-01

Etperinmienal A/.,nimal Model for L)i 4’ara•inc t ,row. NAMRI.-1221. Nasal Aerospace Medical Research L.atratorN. Pensacola. H.I.. Januar, 1976 iAD) A021 287...Berg, HS., Chiang, H.S., Chang, P.C., and Banknieder, A.R., " Nasal Adenocarcinoma in a Taiwan Macaque." Veterinary Pathoiogy, Vol. 14, pp. 294-296...1977. Brown, R.J., Kessler, M.J., and Kupper, J.L., "Myocardial Fibrosarcoma in Rhesus Monkey." Laboratory Anitnal Science, Vol. 27, pp, 524-525, 1977

Antitumour Activity of Poochendurappattai in Albino Rats in Albino Rats

PubMed Central

Alam, Muzaffer; Joy, S; Susan, T.; Brindha, P.; Saraswathy, A.

2000-01-01

The water extract of poochendurappattai was screened for antitumour activity at the doss of 5mg, 10mg, 20mg and 50 mg/kg body weight in rats against methylcholanthrene induced fibrosarcoma. There was 63% regression in the tumour weight at the doses of 10mg and 20 mg/kg body weight. This antitumour activity may be due to compounds like royaleanones since royaleanones are known to possess anticancer activity. Te phytochemical investigation of poochendurappattai revealed the presence of royaleanones. PMID:22557002

Evaluation of (188)Re-labeled NGR-VEGI protein for radioimaging and radiotherapy in mice bearing human fibrosarcoma HT-1080 xenografts.

PubMed

Ma, Wenhui; Shao, Yahui; Yang, Weidong; Li, Guiyu; Zhang, Yingqi; Zhang, Mingru; Zuo, Changjing; Chen, Kai; Wang, Jing

2016-07-01

Vascular endothelial growth inhibitor (VEGI) is an anti-angiogenic protein, which includes three isoforms: VEGI-174, VEGI-192, and VEGI-251. The NGR (asparagine-glycine-arginine)-containing peptides can specifically bind to CD13 (Aminopeptidase N) receptor which is overexpressed in angiogenic blood vessels and tumor cells. In this study, a novel NGR-VEGI fusion protein was prepared and labeled with (188)Re for radioimaging and radiotherapy in mice bearing human fibrosarcoma HT-1080 xenografts. Single photon emission computerized tomography (SPECT) imaging results revealed that (188)Re-NGR-VEGI exhibits good tumor-to-background contrast in CD13-positive HT-1080 tumor xenografts. The CD13 specificity of (188)Re-NGR-VEGI was further verified by significant reduction of tumor uptake in HT-1080 tumor xenografts with co-injection of the non-radiolabeled NGR-VEGI protein. The biodistribution results demonstrated good tumor-to-muscle ratio (4.98 ± 0.25) of (188)Re-NGR-VEGI at 24 h, which is consistent with the results from SPECT imaging. For radiotherapy, 18.5 MBq of (188)Re-NGR-VEGI showed excellent tumor inhibition effect in HT-1080 tumor xenografts with no observable toxicity, which was confirmed by the tumor size change and hematoxylin and eosin (H&E) staining of major mouse organs. In conclusion, these data demonstrated that (188)Re-NGR-VEGI has the potential as a theranostic agent for CD13-targeted tumor imaging and therapy.

Primary Renal Hybrid Low-grade Fibromyxoid Sarcoma-Sclerosing Epithelioid Fibrosarcoma: An Unusual Pediatric Case With EWSR1-CREB3L1 Fusion.

PubMed

Mok, Yingting; Pang, Yin Huei; Sanjeev, Jain Sudhanshi; Kuick, Chik Hong; Chang, Kenneth Tou-En

2018-01-01

Low-grade fibromyxoid sarcoma (LGFMS) and sclerosing epithelioid fibrosarcoma (SEF) are rare tumors with distinct sets of morphological features, both characterized by MUC4 immunoreactivity. Tumors exhibiting features of both entities are considered hybrid LGFMS-SEF lesions. While the majority of LGFMS cases are characterized by FUS-CREB3L2 gene fusions, most cases of pure SEF show EWSR1 gene rearrangements. In the largest study of hybrid LGFMS-SEF tumors to date, all cases exhibited FUS rearrangements, a similar genetic profile to LGFMS. We herein describe the clinicopathological features and genetic findings of a case of primary renal hybrid LGFMS-SEF occurring in a 10-year-old child, with disseminated metastases. Fusion gene detection using a next-generation sequencing-based anchored multiplex PCR technique (Archer FusionPlex Sarcoma Panel) was performed on both the primary renal tumor that showed the morphology of a LGFMS, and a cervical metastasis that showed the morphology of SEF. An EWSR1-CREB3L1 gene fusion occurring between exon 11 of EWSR1 and exon 6 of CREB3L1 was present in both the LGFMS and SEF components. This unusual case provides evidence that a subset of hybrid LGFMS-SEF harbor EWSR1-CREB3L1 gene fusions. In this case, these features were associated with an aggressive clinical course, with disease-associated mortality occurring within 12 months of diagnosis.

Induction of tissue transglutaminase by dexamethasone: its correlation to receptor number and transglutaminase-mediated cell death in a series of malignant hamster fibrosarcomas.

PubMed Central

Johnson, T S; Scholfield, C I; Parry, J; Griffin, M

1998-01-01

Treatment of the hamster fibrosarcoma cell lines (Met B, D and E) and BHK-21 hamster fibroblast cells with the glucocorticoid dexamethasone led to a powerful dose-dependent mRNA-synthesis-dependent increase in transglutaminase activity, which can be correlated with dexamethasone-responsive receptor numbers in each cell line. Increasing the number of dexamethasone-responsive receptors by transfection of cells with the HG1 glucocorticoid receptor protein caused an increase in transglutaminase activity that was proportional to the level of transfected receptor. In all experiments the levels of the tissue transglutaminase-mediated detergent-insoluble bodies was found to be comparable with increases in transglutaminase activity. Despite an increase in detergent-insoluble body formation, an increase in apoptosis as measured by DNA fragmentation was not found. Incubation of cells with the non-toxic competitive transglutaminase substrate fluorescein cadaverine led to the incorporation of this fluorescent amine into cellular proteins when cells were damaged after exposure to trypsin during cell passage. These cross-linked proteins containing fluorescein cadaverine were shown to be present in the detergent-insoluble bodies, indicating that the origin of these bodies is via activation of tissue transglutaminase after cell damage by trypsinization rather than apoptosis per se, since Met B cells expressing the bcl-2 cDNA were not protected from detergent-insoluble body formation. We describe a novel mechanism of cell death related to tissue transglutaminase expression and cell damage. PMID:9512467

Inhibitory Effect of Hizikia fusiformis Solvent-Partitioned Fractions on Invasion and MMP Activity of HT1080 Human Fibrosarcoma Cells

PubMed Central

Lee, Seul-Gi; Karadeniz, Fatih; Oh, Jung Hwan; Yu, Ga Hyun; Kong, Chang-Suk

2017-01-01

Matrix metalloproteinases (MMPs) are endopeptidases that take significant roles in extracellular matrix degradation and therefore linked to several complications such as metastasis of cancer progression, oxidative stress, and hepatic fibrosis. Hizikia fusiformis, a brown algae, was reported to possess bioactivities, including but not limited to, antiviral, antimicrobial, and anti-inflammatory partly due to bioactive polysaccharide contents. In this study, the potential of H. fusiformis against cancer cell invasion was evaluated through the MMP inhibitory effect in HT1080 fibrosarcoma cells in vitro. H. fusiformis crude extract was fractionated with organic solvents, H2O, n-BuOH, 85% aqueous MeOH, and n-hexane (n-Hex). The non-toxicity of the fractions was confirmed by MTT assay. All fractions inhibited the enzymatic activities of MMP-2 and MMP-9 according to the gelatin zymography assay. Cell migration was also significantly inhibited by the n-Hex fraction. In addition, both gene and protein expressions of MMP-2 and -9, and tissue inhibitor of MMPs (TIMPs) were evaluated by reverse transcription-polymerase chain reaction and Western blotting, respectively. The fractions suppressed the mRNA and protein levels of MMP-2, MMP-9 while elevating the TIMP-1 and TIMP-2, with the H2O fraction being the least effective while n-Hex fraction the most. Collectively, the n-Hex fraction from brown algae H. fusiformis could be a potential inhibitor of MMPs, suggesting the presence of various derivatives of polysaccharides in high amounts. PMID:29043215

Lymph node staging of oral and maxillofacial neoplasms in 31 dogs and cats.

PubMed

Herring, Erin S; Smith, Mark M; Robertson, John L

2002-09-01

A retrospective study was performed to report the histologic examination results of regional lymph nodes of dogs and cats with oral or maxillofacial neoplasms. Twenty-eight dogs and 3 cats were evaluated. Histologic examination results of standard and serial tissue sectioning of regional lymph nodes were recorded. When available, other clinical parameters including mandibular lymph node palpation, thoracic radiographs, and pre- and postoperative fine needle aspiration of lymph nodes were compared with the histologic results. Squamous cell carcinoma, fibrosarcoma, and melanoma were the most common neoplasms diagnosed in dogs. Squamous cell carcinoma and fibrosarcoma were diagnosed in cats. Of the palpably enlarged mandibular lymph nodes, 17.0% had metastatic disease histologically. Radiographically evident thoracic metastatic disease was present in 7.4% of cases. Preoperative cytologic evaluation of the mandibular lymph node based on fine needle aspiration concurred with the histologic results in 90.5% of lymph nodes examined. Postoperative cytologic evaluation of fine needle aspirates of regional lymph nodes concurred with the histologic results in 80.6% of lymph nodes examined. Only 54.5% of cases with metastatic disease to regional lymph nodes had metastasis that included the mandibular lymph node. Serial lymph node sectioning provided additional information or metastasis detection. Cytologic evaluation of the mandibular lymph node correlates positively with histology, however results may fail to indicate the presence of regional metastasis. Assessment of all regional lymph nodes in dogs and cats with oral or maxillofacial neoplasms will detect more metastatic disease than assessing the mandibular lymph node only.

Restoration of Tumor Immune Surveillance via Targeting of IL-13Receptor-α2

PubMed Central

Fichtner-Feigl, Stefan; Terabe, Masaki; Kitani, Atsushi; Young, Cheryl A.; Fuss, Ivan; Geissler, Edward K.; Schlitt, Hans-Jürgen; Berzofsky, Jay A.; Strober, Warren

2009-01-01

In previous studies we described a “counter-immunosurveillance” mechanism initiated by tumor-activated, IL-13-producing NKT cells that signal Gr-1+ cells to produce TGF-β1, a cytokine that suppresses the activity of tumor-inhibiting cytolytic CD8+ T cells. Here we show that in two tumor models (the CT-26 metastatic colon cancer and the 15-12RM fibrosarcoma regressor models) this counter-surveillance mechanism requires the expression of a novel IL-13 receptor, IL-13Rα2, on Gr-1intermediate cells, since down-regulation of IL-13Rα2 expression or the AP-1 signal generated by the receptor via in vivo administration of specific siRNA or decoy oligonucleotides leads to loss of TGF-β1 production. Furthermore, acting on prior studies showing that IL-13Rα2 expression is induced (in part) by TNF-α, we show that receptor expression and TGF-β1 production is inhibited by administration of a TNF-α neutralizing substance, TNF-αR-Fc (etanercept). Taking advantage of this latter fact, we then demonstrate in the CT-26 model that counter-immunosurveillance could be inhibited, anti-CT-26-specific CD8+ cytolytic activity restored, and CT-26 metastatic tumor nodules greatly decreased by administration of TNF-αR-Fc. Corroborative data was obtained using the 15-12RM fibrosarcoma model. These studies point to the prevention of metastatic cancer with an available agent with already known clinically acceptable adverse effects and toxicity. PMID:18451175

Bleomycin/interleukin-12 electrochemogene therapy for treating naturally occurring spontaneous neoplasms in dogs.

PubMed

Reed, S D; Fulmer, A; Buckholz, J; Zhang, B; Cutrera, J; Shiomitsu, K; Li, S

2010-07-01

On the basis of superior outcomes from electrochemogene therapy (ECGT) compared with electrochemotherapy in mice, we determined the efficacy of ECGT applied to spontaneous canine neoplasms. Intralesional bleomycin and feline interleukin-12 DNA (fIL-12 DNA) injection combined with translesional electroporation resulted in complete cure of two recurrent World Health Organization stage T(2b)N(0)M(0) oral squamous cell carcinomas (SCCs) and one T(2)N(0)M(0) acanthomatous ameloblastoma. Three remaining dogs, which had no other treatment options, had partial responses to ECGT; one had mandibular T(3b)N(2b)M(1) melanoma with pulmonary and lymph node metastases; one had cubital T(3)N(0)M(1) histiocytic sarcoma with spleen metastases; and one had soft palate T(3)N(0)M(0) fibrosarcoma. The melanoma dog had decrease in size of the primary tumor before recrudescence and euthanasia. The histiocytic sarcoma dog had resolution of the primary tumor, but was euthanized because of metastases 4 months after the only treatment. The dog with T(3)N(0)M(0) fibrosarcoma had tumor regression with recrudescence. Treatment was associated with minimal side effects and was easy to perform. It was associated with repair of bone lysis in cured dogs, it improved quality of life of dogs with partial responses and extended overall survival time. ECGT seems to be a safe and resulted in complete responses in SCC and acanthomatous ameloblastoma.

Preparation and comparative evaluation of 99m Tc-HYNIC-cNGR and 99m Tc-HYNIC-PEG2 -cNGR as tumor-targeting molecular imaging probes.

PubMed

Vats, Kusum; Satpati, Drishty; Sharma, Rohit; Kumar, Chandan; Sarma, Haladhar Dev; Banerjee, Sharmila

2018-02-01

The tripeptide sequence asparagine-glycine-arginine (NGR) specifically recognizes aminopeptidase N (APN or CD13) receptors highly expressed on tumor cells and vasculature. Thus, NGR peptides can precisely deliver therapeutic and diagnostic compounds to CD13 expressing cancer sites. In this regard, 2 NGR peptide ligands, HYNIC-c(NGR) and HYNIC-PEG 2 -c(NGR), were synthesized, radiolabeled with 99m Tc, and evaluated in CD13-positive human fibrosarcoma HT-1080 tumor xenografts. The radiotracers, 99m Tc-HYNIC-c(NGR) and 99m Tc-HYNIC-PEG 2 -c(NGR), could be prepared in approximately 95% radiochemical purity and exhibited excellent in vitro and in vivo stability. The radiotracers were hydrophilic in nature with log P values being -2.33 ± 0.05 and -2.61 ± 0.08. The uptake of 2 radiotracers 99m Tc-HYNIC-c(NGR) and 99m Tc-HYNIC-PEG 2 -c(NGR) was similar in nude mice bearing human fibrosarcoma HT-1080 tumor xenografts, which was significantly reduced (P < .05) during blocking studies. The 2 radiotracers being hydrophilic cleared rapidly from blood, liver, and intestine and were excreted through renal pathway. The pharmacokinetics of 99m Tc-labeled HYNIC peptide could not be modulated through introduction of PEG 2 unit, thus posing a challenge for studies with other linkers towards enhanced tumor uptake and retention. Copyright © 2017 John Wiley & Sons, Ltd.

Fibrosarcoma of the jaws: two cases of primary tumors with intraosseous growth.

PubMed

Angiero, Francesca; Rizzuti, Tommaso; Crippa, Rolando; Stefani, Michele

2007-01-01

Fibrosarcoma (FS) is a malignant mesenchymal neoplasm of the fibroblasts that rarely affects the oral cavity. Two cases of primary FS of the jaws with intraosseous growth (2 men, aged 53 and 71 years) are described. Microscopically, in one case the tumor showed an intense proliferation of spindle-shaped cells, varying little in size and shape and arranged in parallel bands, partly crossing each other, with significant mitotic activity and nuclear pleomorphism; the second case was characterized by low cellularity comprising spindle-shaped cells, deposited in a variably fibrous and myxoid stroma. On immunohistochemistry, cells in both cases were strongly immunoreactive for MIB-1 and vimentin, focally positive for CD68, and negative for S-100 protein, pancytokeratin, HMB45, CD34, desmin, smooth muscle actin (SMA) and epithelial membrane antigen (EMA). Based on clinical, histological and immunohistochemical findings, the final diagnosis was FS in the first case, myxofibrosarcoma in the second. Treatment was radical surgery with mandibular reconstruction. After two years, the first patient displayed multiple metastases and died during the third year after the initial diagnosis; the second patient was still alive and doing well five years after treatment. We discuss the differential diagnosis versus other forms of sarcoma, examining the morphological appearance that is frequently very similar, the immunohistochemical expression of MIB-1, vimentin, S-100, CD-34, CD68, EMA, as well as conventional clinicopathological features that may help to distinguish FS from other sarcomas.

Coagulation activation by MC28 fibrosarcoma cells facilitates lung tumor formation.

PubMed

Amirkhosravi, M; Francis, J L

1995-01-01

Tumor cells interact with the hemostatic system in various ways and may thus influence malignant growth and spread. MC28 fibrosarcoma cells possess a potent procoagulant activity (PCA) and form lung tumors following intravenous injection. The aim of this work was to study the relationship between PCA, intravascular coagulation and lung seeding in the MC28 model. MC28 cells were injected into control, warfarinized and heparinized hooded Lister rats. Coagulation changes were monitored by thromboelastography (TEG) and Sonoclot analysis (SA), lung fibrin formation by light and electron microscopy, tumor seeding by macroscopic counting and tumor cell and platelet deposition in the lungs by radiolabelling. PCA was measured by chromogenic assay. MC28 PCA was characterized as a tissue factor-factor VIIa complex that probably arose during cell culture or disaggregation of solid tumors. Injection of tumor cells caused marked coagulopathy and was rapidly (within 30 min) followed by fibrin deposition in the lungs and accumulation of radiolabelled platelets. Heparin and warfarin significantly reduced lung seeding (p < 0.001) and reduced retention of radiolabelled tumor cells in the pulmonary circulation (p < 0.01). Inhibition of cellular PCA by prior treatment with concanavalin A markedly reduced intravascular coagulation and lung seeding. We conclude that MC28 cells cause intravascular coagulation as a direct result of their procoagulant activity. The data suggest that tumor cells form complexes with platelets and fibrin which are retained in the lungs long enough for extravasation and seeding to occur.(ABSTRACT TRUNCATED AT 250 WORDS)

Osteocalcin and Osteonectin Expression in Canine Osteosarcoma.

PubMed

Wehrle-Martinez, A S; Dittmer, K E; Aberdein, D; Thompson, K G

2016-07-01

Osteosarcoma (OSA) is a malignant heterogeneous primary bone tumor responsible for up to 90% of all primary bone tumors in dogs. In this study, osteocalcin (OC) and osteonectin (ON) immunoreactivity was evaluated in 23 canine OSAs, 4 chondrosarcomas, 4 fibrosarcomas, 2 hemangiosarcomas, and 4 histiocytic sarcomas. The effects of three different decalcification agents (ethylenediaminetetraetic acid [EDTA], formic acid and hydrochloric acid [HCl]) on the immunoreactivity for OC and ON was also assessed. Immunoreactivity to OC was present in 19/23 (83%) cases of OSA and all cases of chondrosarcoma. In three OSAs the extracellular matrix showed immunoreactivity to OC. None of the fibrosarcomas, histiocytic sarcomas or hemangiosarcomas showed immunoreactivity to OC. The sensitivity and specificity for OC in canine OSA in this study was 83% and 71% respectively. For ON, 100% of both OSAs (23/23) and non-OSAs (14/14) showed cytoplasmic immunoreactivity to this antibody, giving a sensitivity of 100% but a complete lack of specificity. There were no significant differences in immunoreactivity for OC and ON between the different decalcification agents used. In conclusion, OC showed high sensitivity for identifying OSA but it failed to distinguish between OSA and chondrosarcoma, and the osteoid produced by neoplastic cells in most cases did not show immunoreactivity to OC. These factors may limit the practical utility of OC in the diagnosis of OSA in dogs when chondrosarcoma is a differential diagnosis. ON showed no specificity in detecting OSA and has little practical application for the diagnosis of OSA in dogs. © The Author(s) 2016.

Chronic inhalation study of mice subjected to diethylhydroxylamine, nitroethane, and diethylamine hydrogen sulfite

DOE Office of Scientific and Technical Information (OSTI.GOV)

Heicklen, J.; Lundgard, R.; Partymiller, K.

1982-04-01

Institute of Cancer Research Swiss strain mice were subjected to the inhalation of 10.3 +/- 3.7 ppm diethylhydroxylamine, 10.1 +/- 4.1 ppm nitroethane, and the vapor of diethylamine hydrogen sulfite for over 2 years. Histopathologic evaluation of all organs indicated only a few significant findings. The incidence of all tumors, as well as subcutaneous tumors (principally fibrosarcomas), increased in exposed males with marginal statistical significance (P = 0.12 and 0.048, respectively). The incidence of all tumors in exposed females decreased with marked statistical significance (P < 0.0005).

Cytology of Bone.

PubMed

Barger, Anne M

2017-01-01

Cytology of bone is a useful diagnostic tool. Aspiration of lytic or proliferative lesions can assist with the diagnosis of inflammatory or neoplastic processes. Bacterial, fungal, and protozoal organisms can result in significant osteomyelitis, and these organisms can be identified on cytology. Neoplasms of bone including primary bone tumors such as osteosarcoma, chondrosarcoma, fibrosarcoma, synovial cell sarcoma, and histiocytic sarcoma and tumors of bone marrow including plasma cell neoplasia and lymphoma and metastatic neoplasia can result in significant bone lysis or proliferation and can be diagnosed effectively with cytology. Copyright © 2016 Elsevier Inc. All rights reserved.

Generalized osteosclerosis in a cat.

PubMed

Hanel, Rita M; Graham, John P; Levy, Julie K; Buergelt, Claus D; Creamer, Jeff

2004-01-01

A 12-year-old, neutered male, domestic long-hair cat was evaluated for a 6-month history of inspiratory stertor and epiphora. In computed tomography of the skull and pelvis, and radiographs of the thorax, right femur and stifle there was generalized osteosclerosis, with obliteration of the nasal turbinates and nasolacrimal duct obstruction. The cat also had a large fibrosarcoma involving the right pelvic limb. Osteosclerosis is a rare disorder that is poorly understood but has been described in several species. Various manifestations, potential causes, and radiologic findings of osteosclerosis are discussed.

Unveiling NIR Aza-Boron-Dipyrromethene (BODIPY) Dyes as Raman Probes: Surface-Enhanced Raman Scattering (SERS)-Guided Selective Detection and Imaging of Human Cancer Cells.

PubMed

Adarsh, Nagappanpillai; Ramya, Adukkadan N; Maiti, Kaustabh Kumar; Ramaiah, Danaboyina

2017-10-12

The development of new Raman reporters has attracted immense attention in diagnostic research based on surface enhanced Raman scattering (SERS) techniques, which is a well established method for ultrasensitive detection through molecular fingerprinting and imaging. Herein, for the first time, we report the unique and efficient Raman active features of the selected aza-BODIPY dyes 1-6. These distinctive attributes could be extended at the molecular level to allow detection through SERS upon adsorption onto nano-roughened gold surface. Among the newly revealed Raman reporters, the amino substituted derivative 4 showed high signal intensity at very low concentrations (ca. 0.4 μm for 4-Au). Interestingly, an efficient nanoprobe has been constructed by using gold nanoparticles as SERS substrate, and 4 as the Raman reporter (4-Au@PEG), which unexpectedly showed efficient recognition of three human cancer cells (lung: A549, cervical: HeLa, Fibrosarcoma: HT-1080) without any specific surface marker. We observed well reflected and resolved Raman mapping and characteristic signature peaks whereas, such recognition was not observed in normal fibroblast (3T3L1) cells. To confirm these findings, a SERS nanoprobe was conjugated with a specific tumour targeting marker, EGFR (Epidermal Growth Factor Receptor), a well known targeted agent for Human Fibrosarcoma (HT1080). This nanoprobe efficiently targeted the surface marker of HT1080 cells, threreby demonstrating its use as an ultrasensitive Raman probe for detection and targeted imaging, leaving normal cells unaffected. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Acute toxic effects of single dose dacarbazine: hematological and histological changes in an animal model.

PubMed

Milijašević, B; Stefanović, D; Lalić-Popović, M; Tomić, Z; Kolarović, J; Lalošević, D; Mikov, M

2014-11-01

Treatment of advanced soft tissue sarcoma usually includes dacarbazine (DTIC), an alkylating agent that methylates DNA and is active during all phases of the cell cycle. Common side effects of DTIC include nausea, vomiting, impaired liver and kidney function, myelosuppression, and pneumonia. There are no accounts, however, of histological and hematological changes caused by DTIC. We investigated acute hematological and morphological changes in different organs and in tumors that were caused by a single dose of DTIC. Adult Syrian golden hamsters were inoculated with a suspension of tumorigenic baby hamster kidney (BHK) cells by subcutaneous injection. On day 14 after inoculation, doses of 1.4, 1.6, 1.8 or 2.0 g/m(2) DTIC were injected intraperitoneally into the hamsters. Hamsters in the control group were injected with physiological saline in the same way. Seven days after drug or saline injection the animals were sacrificed and samples of blood, heart, kidney, liver, lungs, spleen, small intestine and tumor were excised, processed and analyzed. Mitoses were counted using an ocular extension with engraved frame. Anemia, thrombocytopenia and leukocytosis were found in the control group of hamsters with fibrosarcoma, whereas animals with fibrosarcoma treated with DTIC developed anemia, thrombocytopenia and leukopenia. Severe pneumonia and moderate hepatitis were detected in all DTIC treated groups. Effects of DTIC on tumor cells included rounding and enlargement of nuclei and rarefaction of chromatin. The number of mitoses was reduced with increasing doses of DTIC. Hepatitis, myelosuppression, pneumonia, and dose-related inhibition of tumor cell proliferation were observed after a single dose of DTIC.

Immunohistochemical expression of c-KIT protein in feline soft tissue fibrosarcomas.

PubMed

Smith, A J; Njaa, B L; Lamm, C G

2009-09-01

C-KIT is the cellular homolog of the feline sarcoma viral oncogene v-KIT, which encodes the tyrosine kinase receptor protein KIT. Mutations and varied expression of this gene have been demonstrated within multiple neoplasms in people and domestic animals. The purpose of this study was to determine if KIT protein is expressed in feline soft tissue fibrosarcomas (ST FSA) using immunohistochemistry (IHC). The computer database at the Oklahoma Animal Disease Diagnostic Laboratory was searched from January 1, 2006, to December 31, 2007, for any domestic cat with an ST FSA. Routinely stained slides from 46 feline ST FSAs were reviewed and graded based on the scale outlined by Kuntz et al. Immunohistochemistry for KIT protein was performed on one representative section from each cat. There were a total of 12/46 (26%) cats that were immunoreactive for KIT. Immunoreactivity was detected in greater than 80% of the neoplastic cells in 4/46 (9%) cats. Immunoreactivity was detected in less than 10% of the neoplastic cells in 8/46 (17%) cats. Immunoreactivity was characterized by evenly distributed cytoplasmic stippling within the neoplastic spindle-shaped cells and/or multinucleated giant cells. Based on these results, KIT immunoreactivity can be detected within feline ST FSAs using IHC. The results of this study also indicate that KIT immunoreactivity in feline ST FSA does not correlate with the histologic grade (P = .141, X(2) = 2.166), survivability (P = .241, X(2) = 1.373), or whether the neoplasm was a spontaneous or an injection site FSA (P = .074, X(2) = 3.184).

Hydrophilic extract from Posidonia oceanica inhibits activity and expression of gelatinases and prevents HT1080 human fibrosarcoma cell line invasion

PubMed Central

Barletta, Emanuela; Ramazzotti, Matteo; Fratianni, Florinda; Pessani, Daniela; Degl'Innocenti, Donatella

2015-01-01

Posidonia oceanica (L.) Delile is an endemic Mediterranean sea-grass distributed in the infralittoral zones, where it forms meadows playing a recognized ecological role in the coastal marine habitat. Although its use as a traditional herbal remedy is poorly documented, recent literature reports interesting pharmacological activities as antidiabetic, antioxidant and vasoprotective. Differently from previous literature, this study presents a hydrophilic extraction method that recovers metabolites that may be tested in biological buffers. We showed for the first time in the highly invasive HT1080 human fibrosarcoma cell line that our hydrophilic extract from P. oceanica was able to strongly decrease gene and protein expression of gelatinases MMP-2 and MMP-9 and to directly inhibit in a dose-dependent manner gelatinolytic activity in vitro. Moreover, we have revealed that our extract strongly inhibited HT1080 cell migration and invasion. Biochemical analysis of the hydrophilic extract showed that catechins were the major constituents with minor contribution of gallic acid, ferulic acid and chlorogenic plus a fraction of uncharacterized phenols. However, if each individual compound was tested independently, none by itself was able to induce a direct inhibition of gelatinases as strong as that observed in total extract, opening up new routes to the identification of novel compounds. These results indicate that our hydrophilic extract from P. oceanica might be a source of new pharmacological natural products for treatment or prevention of several diseases related to an altered MMP-2 and MMP-9 expression. PMID:26176658

Comparative plasma and tissue distribution of Sun Pharma's generic doxorubicin HCl liposome injection versus Caelyx® (doxorubicin HCl liposome injection) in syngeneic fibrosarcoma-bearing BALB/c mice and Sprague-Dawley rats.

PubMed

Burade, Vinod; Bhowmick, Subhas; Maiti, Kuntal; Zalawadia, Rishit; Jain, Deepak; Rajamannar, Thennati

2017-05-01

The liposomal formulation of doxorubicin [doxorubicin (DXR) hydrochloride (HCl) liposome injection, Caelyx ® ] alters the tissue distribution of DXR as compared with nonliposomal DXR, resulting in an improved benefit-risk profile. We conducted studies in murine models to compare the plasma and tissue distribution of a proposed generic DXR HCl liposome injection developed by Sun Pharmaceuticals Industries Limited (SPIL DXR HCl liposome injection) with Caelyx ® . The plasma and tissue distributions of the SPIL and reference DXR HCl liposome injections were compared in syngeneic fibrosarcoma-bearing BALB/c mice and Sprague-Dawley rats. Different batches and different lots of the same batch of the reference product were also compared with each other. The SPIL and reference DXR HCl liposome injections exhibited generally comparable plasma and tissue distribution profiles in both models. While minor differences were observed between the two products in some tissues, different batches and lots of the reference product also showed some differences in the distribution of various analytes in some tissues. The ratios of estimated free to encapsulated DXR for plasma and tissue were generally comparable between the SPIL and reference DXR HCl liposome injections in both models, indicating similar extents of absorption into the tissues and similar rates of drug release from liposomes. The plasma and tissue distribution profiles of the SPIL and reference DXR HCl liposome injections were shown to be generally comparable. Inconsistencies between the products observed in some tissues were thought to be due to biological variation.

Junctional adhesion molecule-C promotes metastatic potential of HT1080 human fibrosarcoma.

PubMed

Fuse, Chiaki; Ishida, Yuuki; Hikita, Tomoya; Asai, Tomohiro; Oku, Naoto

2007-03-16

The junctional adhesion molecule (JAM) family is a key molecule in a process called transendothelial migration or diapedesis. Here, we report implications of JAM-C in cancer metastasis. We first determined the mRNA expression of JAMs in 19 kinds of cancer cell lines. JAM-C was expressed in most of tumors having potent metastatic properties. Especially in murine K-1735 melanoma cell lines, the highly metastatic sublines (M2 and X21) strongly expressed JAM-C when compared with the poorly metastatic ones (C-10 and C23). Next, we investigated the role of JAM-C in cancer metastasis by using human JAM-C (hJAM-C) gene-transfected HT1080 fibrosarcoma cells. In comparison with mock-transfected HT1080 cells, these cells showed a significant increase in the adhesion to various extracellular substrates and the invasion across a Matrigel-coated membrane. The knockdown of hJAM-C using small interfering RNA resulted in the suppression of both the adhesion and the invasion of HT1080 cells, suggesting that endogenous hJAM-C might be involved in tumor metastasis. Finally, we studied the role of hJAM-C in an in vivo experimental metastatic model. The results showed that the overexpression of hJAM-C in HT1080 cells significantly decreased the life spans of the tumorbearing mice. In contrast, the knockdown of hJAM-C in HT1080 cells suppressed the weight gain of the lungs with metastatic colonies. We conclude that the expression of JAM-C promotes metastasis by enhancing both the adhesion of cancer cells to extracellular matrices and the subsequent invasion.

Tumor-Mediated Suppression of Dendritic Cell Vaccines

DTIC Science & Technology

2005-03-01

presence of 10 ng/ml of TGF-P for 6 days. (A) DCs were incubated with 2x10 5 splenic T cells isolated from C57/ BL6 mice for 5 days with the addition...intensity (MFI) at 37°C minus 4°C. D, DCs were incubated with 2 X 105 splenic T cells isolated from C57/ BL6 mice for 5 days with the addition of [3H...or MCA-106 fibrosarcoma 1863 TGF-13 NEUTRALIZING ANTIBODY AND DCs yields equally effective vaccines against B16 tumors in mice. J. Surg., 68: 79-91, 20

The Acute, Delayed Neurotoxicity Evaluation of Two Jet Engine Oil Formulations

DTIC Science & Technology

1990-04-01

humans after chronic exposure to these compounds. Similar neurotoxic effects have been demonstrated in adult chickens and cats after exposure to TOCP...salpingitis 0 1 0 0 0 0 0 0 0 0 0 0 Skin 2 3 3 2 4 3 1 2 2 3 1 5 Fibrosarcoma 0 0 1 0 0 0 0 0 0 0 0 0 *The number of animals in which the organ was examined...REFERENCES Beresford, W.A. and P. Glees. 1963. Degeneration in the Long Tracts of the Cords of the Chicken and Cat After Triorthocresyl phosphate

Role of cdc25 Phosphatases in Human Breast Cancer

DTIC Science & Technology

2008-05-01

Cdc25C in these assays, their cat - alytically inactive mutants Cdc25B (C488S) and Cdc25C (C377S) (referred to as mt25B and mt25C) were generated and...chimeras. B and C, N25B and N25C (B) and their corresponding cat - alytically inactive mutants N25B/C and N25C/B (C). Cdc25B Inhibits Cell...HCT116 cells because similar results were obtained using U2OS (osteosarcoma) andHT1080 ( fibrosarcoma ) cells (data not shown). The level of Cdc25B

Aggressive fibromatosis (fibrosarcoma) of the facial nerve.

PubMed

Pulec, J L

1993-07-01

Aggressive fibromatosis of the facial nerve is a very rare tumor. Three cases have been previously reported. The tumor is locally recurrent and often has a fatal outcome. This report is of a ten-year-old boy whose tumor originally developed in the parotid area with subsequent spread to the base of the skull, the neck and the cerebellopontine angle. Treatment was by wide surgical excision, radiation therapy and chemotherapy. Despite treatment, the patient died. The clinical features of this case will be described. Only wide surgical excision early in the course of the disease may offer a chance for cure.

Odontogenic Cysts and Neoplasms.

PubMed

Bilodeau, Elizabeth Ann; Collins, Bobby M

2017-03-01

This article reviews a myriad of common and uncommon odontogenic cysts and tumors. The clinical presentation, gross and microscopic features, differential diagnosis, prognosis, and diagnostic pitfalls are addressed for inflammatory cysts (periapical cyst, mandibular infected buccal cyst/paradental cyst), developmental cysts (dentigerous, lateral periodontal, glandular odontogenic, orthokeratinized odontogenic cyst), benign tumors (keratocystic odontogenic tumor, ameloblastoma, adenomatoid odontogenic tumor, calcifying epithelial odontogenic tumor, ameloblastic fibroma and fibroodontoma, odontoma, squamous odontogenic tumor, calcifying cystic odontogenic tumor, primordial odontogenic tumor, central odontogenic fibroma, and odontogenic myxomas), and malignant tumors (clear cell odontogenic carcinoma, ameloblastic carcinoma, ameloblastic fibrosarcoma). Copyright © 2016 Elsevier Inc. All rights reserved.

Oral and maxillofacial sclerosing epithelioid fibrosarcoma: report of five cases.

PubMed

Folk, Gretchen S; Williams, Stephen B; Foss, Robert B; Fanburg-Smith, Julie C

2007-09-01

Sclerosing epithelioid fibrosarcoma (SEF) has distinctive morphology and occurs mainly in deep soft tissue of adult extremities. Approximately 59 cases of SEF have been reported, with only 12 previously described in head and neck locations. Lesions involving the oral and maxillofacial region (OMFR) and intraosseous examples are rare. We present five cases of OMFRSEF. The OMF Pathology Department Registry was searched for cases coded from 1990 to the present as "SEF," "fibrosarcoma not otherwise specified" or "neoplasm of uncertain histiogenesis." Inclusion required OMFR location, an abundantly sclerotic sarcoma with epithelioid features, and lack of other phenotype by immunohistochemistry. Five cases of SEF included 3 males and 2 females. The age of the patients were: 19, 22, 35, 47 and 47 years. Tumor location included the infra-temporal fossa, buccal mucosa (recurrence extending into bone), anterior mandible (intraosseous primary, focally extending into soft tissue), and left parotid and submandibular gland (with metaplastic bone) regions. Tumor sizes ranged from 1.0 to 5.7 cm, median 3.5 cm. Histologically, the tumors were well delineated and multinodular, separated by fibrous septae. The spindled to primarily epithelioid tumor cells formed moderately cellular sheets and cords of irregularly contoured medium to large, round to oval, occasionally overlapping nuclei, indistinct nucleoli, wispy eosinophilic (retracting) cytoplasm, and distinctive cytoplasmic borders, embedded in osteoid-like stroma. Hemangiopericytoid (HPC-like) vessels were observed. Despite numerous apoptotic cells, mitoses were generally low; necrosis was present in two cases. Three tumors were graded as 2/3 and two 1/3. Immunohistochemically, the tumor cells were positive for vimentin, 1 case focally for CD34, whereas all cases were negative for S100 protein, keratins, EMA, desmin, and SMA. Wide or radical excision was performed with no adjuvant therapy. Follow-up revealed that 4 cases recurred at a range of 12-120 months. One case had no recurrent/residual disease at 3 months. Metastatic disease was present in 2 cases, to chest wall and lumbar/thoracic spine at 12 and 21 months, respectively. One patient died of disease complications at 15 months. OMFRSEF occur in adults in various locations, but with a common propensity to involve bone; there is recurrent potential and morbidity with higher grade lesions. The differential diagnosis for these tumors in this site includes sclerosing carcinoma, Ewing/PNET, osteosarcoma, osteoblastoma, and benign and malignant myoepithelial salivary gland tumors. The collagen, focal spindle cell features, HPC-like vasculature, and weak focal CD34 reactivity in one case might have raised a possible relationship between OMFRSEF and low grade malignant solitary fibrous tumor, but the intraosseous propensity, epithelioid features and relative lack of CD34 make this a distinctive entity.

Nano-Scaled Particles of Titanium Dioxide Convert Benign Mouse Fibrosarcoma Cells into Aggressive Tumor Cells

PubMed Central

Onuma, Kunishige; Sato, Yu; Ogawara, Satomi; Shirasawa, Nobuyuki; Kobayashi, Masanobu; Yoshitake, Jun; Yoshimura, Tetsuhiko; Iigo, Masaaki; Fujii, Junichi; Okada, Futoshi

2009-01-01

Nanoparticles are prevalent in both commercial and medicinal products; however, the contribution of nanomaterials to carcinogenesis remains unclear. We therefore examined the effects of nano-sized titanium dioxide (TiO2) on poorly tumorigenic and nonmetastatic QR-32 fibrosarcoma cells. We found that mice that were cotransplanted subcutaneously with QR-32 cells and nano-sized TiO2, either uncoated (TiO2−1, hydrophilic) or coated with stearic acid (TiO2−2, hydrophobic), did not form tumors. However, QR-32 cells became tumorigenic after injection into sites previously implanted with TiO2−1, but not TiO2−2, and these developing tumors acquired metastatic phenotypes. No differences were observed either histologically or in inflammatory cytokine mRNA expression between TiO2−1 and TiO2−2 treatments. However, TiO2−2, but not TiO2−1, generated high levels of reactive oxygen species (ROS) in cell-free conditions. Although both TiO2−1 and TiO2−2 resulted in intracellular ROS formation, TiO2−2 elicited a stronger response, resulting in cytotoxicity to the QR-32 cells. Moreover, TiO2−2, but not TiO2−1, led to the development of nuclear interstices and multinucleate cells. Cells that survived the TiO2 toxicity acquired a tumorigenic phenotype. TiO2-induced ROS formation and its related cell injury were inhibited by the addition of antioxidant N-acetyl-l-cysteine. These results indicate that nano-sized TiO2 has the potential to convert benign tumor cells into malignant ones through the generation of ROS in the target cells. PMID:19815711

Enhanced expression of the urokinase-type plasminogen activator gene and reduced colony formation in soft agar by ectopic expression of PU.1 in HT1080 human fibrosarcoma cells.

PubMed Central

Kondoh, N.; Yamada, T.; Kihara-Negishi, F.; Yamamoto, M.; Oikawa, T.

1998-01-01

To investigate the cell biological function of PU.1, a member of the Ets family of transcription factors, a vector capable of expressing the protein was transfected into HT1080 human fibrosarcoma cells. Exogenous expression of PU.1 in HT1080 cells reduced colony-forming efficiency but stimulated cell migration in soft agar, although it did not affect cell growth in adherent culture. Expression of the urokinase-type plasminogen activator (uPA) mRNA, which is known to be correlated with cell migration and invasion, was enhanced in PU.1 transfectants compared with mock transfectants. Run-on analysis demonstrated that uPA transcription was unaffected by PU.1, suggesting that this enhancement mainly occurs at a post-transcriptional level. On the other hand, treatment of HT1080 cells with the synthetic glucocorticoid dexamethasone (DEX; 10(-7) M) significantly reduced uPA gene expression at a transcriptional level. Furthermore, DEX inhibited cell migration in soft agar without affecting cell growth. These negative effects of DEX on uPA expression and cell migration were alleviated by the expression of PU.1 in HT1080 cells, whereas expression of the N-ras oncogene, which is responsible for maintenance of the transformed phenotypes in HT1080 cells, was unaffected by PU.1 expression or DEX treatment in the cells. Our results suggest that expression of PU.1 can stimulate uPA gene expression at the post-transcriptional level, which may subsequently lead to activation of cell motility and/or reduced cell-cell adhesion, but reduces anchorage-independent growth of HT1080 cells. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:9743289

Structure and function of three novel MHC class I antigens derived from a C3H ultraviolet-induced fibrosarcoma

PubMed Central

1986-01-01

The UV-induced, C3H fibrosarcoma, 1591, expresses at least three unique MHC class I antigens not found on normal C3H tissue. Here we report the complete DNA sequence of the three novel class I genes encoding these molecules, and describe in detail the recognition of the individual products by tumor-reactive and allospecific CTL. Remarkably, although C3H does not appear to express H-2L locus information, this C3H tumor expresses two distinct antigens, termed A149 and A166, which are extremely homologous to each other and to the H-2Ld antigen from BALB/c. The gene encoding the third novel class I antigen from 1591, A216, is quite homologous to H-2Kk) throughout its 3' end. Since all three of these genes account for polymorphic restriction fragments not found in C3H, it is likely that they were derived by recombination from the endogenous class I genes of C3H. The DNA sequence homology of A149, A166, and H-2Ld is especially significant given the functional conservation observed between the products of these genes. Limited sequence substitutions appear to correlate with some of the discrete serological differences observed between these molecules. In addition, both A149 and A166 crossreact, but to differing extents, with H-2Ld at the level of T cell recognition. Our results are consistent with the view that CTL recognize complex conformational determinants on class I molecules, but extend previous observations by comparing a set of antigens with discrete and overlapping structural and functional differences. PMID:3489061

The effect of radiation therapy combined with natural killer cells against spontaneous murine fibrosarcoma.

PubMed

Nakagawa, K; Yoshida, F; Omori, N; Tsunoda, T; Nose, T

1990-01-01

The effect of radiation therapy combined with lymphoid cells against spontaneous murine fibrosarcoma (FSa-II) was investigated both in vivo and in vitro. In the in vivo experiment, syngeneic C3H mice were divided into 3 groups. Animals in the first group were injected with 1 x 10(5) tumor cells into the right hind leg. Animals in the second and third groups were injected with 1 x 10(5) tumor cells mixed with 1 x 10(7) normal lymphoid cells (NLC) or effector lymphoid cells (ELC), respectively. ELC were obtained from spleen and lymph nodes of FSa-II-bearing mice and incubated in vitro for 40 hr to eliminate suppressor T cell function. NLC were obtained from normal mice and incubated in the same way. Irradiation was given using 137Cs unit 3 days after cell inoculation. 12 out of 14 mice (85.7%) inoculated with tumor cells mixed with NLC did not show any tumor growth at 60 Gy local irradiation. 12 out of 21 mice (57.1%) inoculated with tumor cells alone and 6 out of 10 (60%) with tumor cells mixed with ELC rejected tumors at the same radiation dose. This synergistic effect with NLC was not observed when NLC was inoculated after irradiation, indicating that lymphoid cells should be in contact with tumor cells before irradiation. In the 51Cr release assay, lymphoid cells obtained from whole body irradiated (WBI) mice showed 17.8% lysis without irradiation and 28.8% lysis at 5 Gy irradiation. Untreated NLC showed almost no cytotoxic effect at the same radiation dose. This synergistic effect disappeared when WBI lymphoid cells were treated with anti asialo GM1 and complement.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of 14-kDa and 47-kDa protein molecules of age garlic extract on peritoneal macrophages.

PubMed

Daneshmandi, Saeed; Hajimoradi, Monire; Ahmadabad, Hasan Namdar; Hassan, Zuhair Mohammad; Roudbary, Maryam; Ghazanfari, Tooba

2011-03-01

Garlic (Allium sativum), traditionally being used as a spice worldwide, has different applications and is claimed to possess beneficial effects in several health ailments such as tumor and atherosclerosis. Garlic is also an immunomodulator and its different components are responsible for different properties. The present work aimed to assess the effect of protein fractions of garlic on peritoneal macrophages. 14-kDa and 47-kDa protein fractions of garlic were purified. Mice peritoneal macrophages were lavaged and cultured in a microtiter plate and exposed to different concentrations of garlic proteins. MTT assay was performed to evaluate the viability of macrophage. The amount of nitric oxide (NO) was detected in culture supernatants of macrophages by Griess reagent and furthermore, the cytotoxicity study of culture supernatants was carried out on WEHI-164 fibrosarcoma cell line as tumor necrosis factor-α bioassay. MTT assay results for both 14-kDa and 47-kDa protein fractions of stimulated macrophages were not significant (P > 0.05). Both 14-kDa and 47-kDa fractions significantly suppressed production of NO from macrophages (P = 0.007 and P = 0.003, respectively). Cytotoxicity of macrophages' supernatant on WEHI-164 fibrosarcoma cells was not affected by garlic protein fractions (P = 0.066 for 14-kDa and P = 0.085 for 47-kDa fractions). according to our finding, 14-kDa and 47-kDa fractions of aged garlic extract are able to suppress NO production from macrophages, which can be used as a biological advantage. These molecules had no cytotoxic effect on macrophages and do not increase tumoricidal property of macrophages.

CREG1 enhances p16INK4a-induced cellular senescence

PubMed Central

Moolmuang, Benchamart

2011-01-01

Cellular senescence is an irreversible growth arrest that is activated in normal cells upon shortening of telomere and other cellular stresses. Bypassing cellular senescence is a necessary step for cells to become immortal during oncogenic transformation. During the spontaneous immortalization of Li-Fraumeni Syndrome (LFS) fibroblasts, we found that CREG1 (Cellular Repressor of E1A-stimulated Genes 1) expression was decreased during immortalization and increased in senescence. Moreover, we found that repression of CREG1 expression occurs via an epigenetic mechanism, promoter DNA methylation. Ectopic expression of CREG1 in the immortal LFS cell lines decreases cell proliferation but does not directly induce senescence. We confirmed this in osteosarcoma and fibrosarcoma cancer cell lines, cancers commonly seen in Li-Fraumeni Syndrome. In addition, we found that p16INK4a is also downregulated in immortal cells and that coexpression of CREG1 and p16INK4a, an inhibitor of CDK4/6 and Rb phosphorylation, has a greater effect than either CREG1 and p16INK4a alone to reduce cell growth, induce cell cycle arrest and cellular senescence in immortal LFS fibroblasts, osteosarcoma and fibrosarcoma cell lines. Moreover, cooperation of CREG1 and p16INK4a inhibits the expression of cyclin A and cyclin B by inhibiting promoter activity, thereby decreasing mRNA and protein levels; these proteins are required for S-phase entry and G2/M transition. In conclusion, this is the first evidence to demonstrate that CREG1 enhances p16INK4a-induced senescence by transcriptional repression of cell cycle-regulated genes. PMID:21263217

Use of chloro-aluminum sulfonated phthalocyanine as a photosensitizer in the treatment of malignant tumors in dogs and cats

NASA Astrophysics Data System (ADS)

Peavy, George M.; Klein, Mary K.; Newman, H. C.; Roberts, Walter G.; Berns, Michael W.

1991-05-01

Chloro-aluminum sulfonated phthalocyanine (CASPc) has been proposed as a photosensitizing agent for photodynamic therapy (PDT) of neoplasia. This paper reviews the results of PDT treatment using CASPc as a photosensitizing agent in the treatment of 15 cats representing 23 sites of facial, solar induced squamous cell carcinoma, 4 dogs with hemangiopericytomas, 3 dogs with fibrosarcomas, and 1 dog with multiple cutaneous mast cell tumors. The results of this study to date suggest that CASPc is a good photosensitizing agent for the treatment of some forms of spontaneously occurring malignant neoplasia and should be more thoroughly evaluated for this purpose.

Outcomes of cats with oral tumors treated with mandibulectomy: 42 cases.

PubMed

Northrup, Nicole C; Selting, Kimberly A; Rassnick, Kenneth M; Kristal, Orna; O'Brien, Maura G; Dank, Gillian; Dhaliwal, Ravinder S; Jagannatha, Shyla; Cornell, Karen K; Gieger, Tracy L

2006-01-01

Medical records of 42 cats treated with mandibulectomy for oral neoplasia at eight institutions were reviewed to determine morbidity, progression-free interval, and survival time. Progression-free and survival rates at 1 and 2 years were 56% and 49%, and 60% and 57%, respectively. Cats with squamous cell carcinoma had significantly shorter survival than cats with fibrosarcoma or osteosarcoma. Seventy-two percent of cats were dysphagic or inappetent immediately postoperatively, and 12% never regained the ability to eat. Despite acute morbidity in 98% and long-term morbidity in 76% of cats, 83% of the 30 owners providing information were satisfied with the outcome of mandibulectomy.

Feline vaccine-associated fibrosarcoma: an ultrastructural study of 20 tumors (1996-1999).

PubMed

Madewell, B R; Griffey, S M; McEntee, M C; Leppert, V J; Munn, R J

2001-03-01

Twenty feline vaccine-associated sarcomas were examined by transmission electron microscopy. Tumors contained pleomorphic spindle cells, histiocytoid cells, and giant cells. Most tumors contained myofibroblasts, which had morphologic features similar to those of fibroblasts. These cells were further distinguished by subplasmalemmal dense plaques and thin cytoplasmic actin myofilaments organized as elongated bundles concentrated at irregular intervals forming characteristic dense bodies. Intracellular crystalline particulate material was found in 5 of the 20 tumors. Energy dispersive X-ray spectroscopy was used to identify the crystalline material within one tumor as aluminum-based. One tumor from a feline leukemia virus-infected cat contained budding and immature retroviral particles.

Central hemimaxillectomy and reconstruction using a superficial temporal artery axial pattern flap in a domestic short hair cat.

PubMed

Lester, S; Pratschke, K

2003-08-01

A 2-year-old, neutered male domestic short hair cat presented with a large mass involving the right upper lip and underlying gingiva. A previous attempt at mass excision had failed, and the histopathological diagnosis was reported to be a fibrosarcoma. The cat was otherwise in good health.A central hemimaxillectomy was performed with extensive soft-tissue dissection and maxillofacial reconstruction achieved using an axial pattern flap based on the superficial temporal artery. This is the first reported clinical case of the use of the superficial temporal artery axial pattern flap in the cat. Histopathology identified a periodontal fibromatous epulis.

Tumours of the soft (mesenchymal) tissues

PubMed Central

Weiss, E.

1974-01-01

This is a classification of tumours of fibrous tissue, fat, muscle, blood and lymph vessels, and mast cells, irrespective of the region of the body in which they arise. Tumours of fibrous tissue are divided into fibroma, fibrosarcoma (including “canine haemangiopericytoma”), other sarcomas, equine sarcoid, and various tumour-like lesions. The histological appearance of the tumours is described and illustrated with photographs. ImagesFig. 1Fig. 2Fig. 3Fig. 4Fig. 9Fig. 10Fig. 11Fig. 12Fig. 17Fig. 18Fig. 19Fig. 20Fig. 5Fig. 6Fig. 7Fig. 8Fig. 13Fig. 14Fig. 15Fig. 16 PMID:4371740

APOBEC3-mediated hypermutation of retroviral vectors produced from some retrovirus packaging cell lines.

PubMed

Miller, A D; Metzger, M J

2011-05-01

APOBEC3 proteins are packaged into retrovirus virions and can hypermutate retroviruses during reverse transcription. We found that HT-1080 human fibrosarcoma cells hypermutate retroviruses, and that the HT-1080 cell-derived FLYA13 retrovirus packaging cells also hypermutate a retrovirus vector produced using these cells. We found no hypermutation of the same vector produced by the mouse cell-derived packaging line PT67 or by human 293 cells transfected with the vector and retrovirus packaging plasmids. We expect that avoidance of vector hypermutation will be particularly important for vectors used in gene therapy, wherein mutant proteins might stimulate deleterious immune responses.

H3.1 K36M mutation in a congenital-onset soft tissue neoplasm.

PubMed

Kernohan, Kristin D; Grynspan, David; Ramphal, Raveena; Bareke, Eric; Wang, You Chang; Nizalik, Elizabeth; Ragoussis, Jiannis; Jabado, Nada; Boycott, Kym M; Majewski, Jacek; Sawyer, Sarah L

2017-12-01

We describe a patient who presented with a congenital soft tissue lesion initially diagnosed as infantile fibromatosis at 15 days of age. Unusually, the mass demonstrated malignant progression leading to death at 20 months of age. Biological progression to malignancy is not known to occur in fibromatosis, and fibrosarcoma is not known to progress from a benign lesion. Whole-exome sequencing of the tumor identified a driver mutation in histone H3.1 at lysine (K)36. Our findings support the link between oncohistones and infantile soft tissue tumors and provide additional evidence for the oncogenic effects of p.K36M in H3 variants. © 2017 Wiley Periodicals, Inc.

Postirradiation malignant fibrous histiocytoma arising in juvenile nasopharyngeal angiofibroma and producing alpha-1-antitrypsin.

PubMed

Spagnolo, D V; Papadimitriou, J M; Archer, M

1984-03-01

A fatal nasopharyngeal malignant fibrous histiocytoma developed in a young male after irradiation of juvenile nasopharyngeal angiofibroma diagnosed 5 years earlier. The sarcoma extended from the nasopharynx into the floor of the pituitary fossa and into both parasellar regions. There was no clinical evidence of any distant spread. Many of the malignant cells contained cytoplasmic granular and globular PAS-positive inclusions shown to be alpha-1-antitrypsin immunohistochemically. Ultrastructurally, this probably corresponded to electron-dense material with distinctive patterns and which had accumulated within distended ergastoplasmic cisternae of the neoplastic cells. Three previously reported case of postirradiation sarcomas arising in nasopharyngeal angiofibroma were said to be fibrosarcomas and none produced alpha-1-antitrypsin.

Differential Diagnosis of Benign Spindle Cell Lesions.

PubMed

Magro, Gaetano

2018-03-01

Spindle cell lesions of the breast cover a wide spectrum of diseases ranging from reactive tumor-like lesions to high-grade malignant tumors. The recognition of the benign spindle cell tumor-like lesions (nodular fasciitis; reactive spindle cell nodule after biopsy, inflammatory pseudotumor/inflammatory myofibroblastic tumor; fascicular variant of pseudoangiomatous stromal hyperplasia) and tumors (myofibroblastoma, benign fibroblastic spindle cell tumor, leiomyoma, schwannoma, spindle cell lipoma, solitary fibrous tumor, myxoma) is crucial to avoid confusion with morphologically similar but more aggressive bland-appearing spindle cell tumors, such as desmoid-type fibromatosis, low-grade (fibromatosis-like) spindle cell carcinoma, low-grade fibrosarcoma/myofibroblastic sarcoma and dermatofibrosarcoma protuberans. Copyright © 2017 Elsevier Inc. All rights reserved.

Modified lateral orbitotomy for removal of orbital neoplasms in two dogs.

PubMed

Gilger, B C; Whitley, R D; McLaughlin, S A

1994-01-01

A simplified lateral orbitotomy is described that decreases surgical time and lessens tissue dissection, yet maintains the exposure to the orbit provided by other orbitotomy techniques. The approach involves cutting the orbital ligament, incising the temporalis aponeurosis from the dorsal zygomatic arch, making parallel zygomatic arch osteotomies, and reflecting the zygomatic arch ventrally. Closure of the wound involves wiring the zygomatic arch back into place. This orbitotomy procedure provides excellent exposure for removal or biopsy of orbital masses. The use of this technique for surgical excision of orbital masses in two dogs, one with an adenoma of the third eyelid gland and one with an orbital fibrosarcoma, and their subsequent management is described.

A Method to Convert MRI Images of Temperature Change Into Images of Absolute Temperature in Solid Tumors

PubMed Central

Davis, Ryan M.; Viglianti, Benjamin L.; Yarmolenko, Pavel; Park, Ji-Young; Stauffer, Paul; Needham, David; Dewhirst, Mark W.

2013-01-01

Purpose During hyperthermia (HT), the therapeutic response of tumors varies substantially within the target temperature range (39–43°C). Current thermometry methods are either invasive or measure only temperature change, which limits the ability to study tissue responses to HT. This study combines manganese-containing low-temperature sensitive liposomes (Mn-LTSL) with proton resonance frequency shift (PRFS) thermometry to measure absolute temperature in tumors with high spatial and temporal resolution using MRI. Methods Liposomes were loaded with 300mM MnSO4. The phase transition temperature (Tm) of Mn-LTSL samples was measured by differential scanning calorimetry (DSC). The release of manganese from Mn-LTSL in saline was characterized with inductively-coupled plasma atomic emission spectroscopy. A 2T GE small animal scanner was used to acquire dynamic T1-weighted images and temperature change images of Mn-LTSL in saline phantoms and fibrosarcoma-bearing Fisher 344 rats receiving hyperthermia after Mn-LTSL injection. Results The Tm of Mn-LTSL in rat blood was 42.9 ± 0.2 °C (DSC). For Mn-LTSL samples (0.06mM – 0.5mM Mn2+ in saline) heated monotonically from 30°C to 50°C, a peak in the rate of MRI signal enhancement occurred at 43.1 ± 0.3 °C. The same peak in signal enhancement rate was observed during heating of fibrosarcoma tumors (N=3) after injection of Mn-LTSL, and the peak was used to convert temperature change images into absolute temperature. Accuracies of calibrated temperature measurements were in the range 0.9 – 1.8°C. Conclusion The release of Mn2+ from Mn-LTSL affects the rate of MR signal enhancement which enables conversion of MRI-based temperature change images to absolute temperature. PMID:23957326

Uptake and subcellular distribution of [3H]arachidonic acid in murine fibrosarcoma cells measured by electron microscope autoradiography

PubMed Central

1985-01-01

We have used quantitative electron microscope autoradiography to study uptake and distribution of arachidonate in HSDM1C1 murine fibrosarcoma cells and in EPU-1B, a mutant HSDM1C1 line defective in high affinity arachidonate uptake. Cells were labeled with [3H]arachidonate for 15 min, 40 min, 2 h, or 24 h. Label was found almost exclusively in cellular phospholipids; 92-96% of incorporated radioactivity was retained in cells during fixation and tissue processing. All incorporated radioactivity was found to be associated with cellular membranes. Endoplasmic reticulum (ER) contained the bulk of [3H]arachidonate at all time points in both cell types, while mitochondria, which contain a large portion of cellular membrane, were labeled slowly and to substantially lower specific activity. Plasma membrane (PM) also labeled slowly, achieving a specific activity only one-sixth that of ER at 15 min in HSDM1C1 cells (6% of total label) and one-third of ER in EPU-1B (10% of total label). Nuclear membrane (NM) exhibited the highest specific activity of labeling at 15 min in HSDM1C1 cells (twice that of ER) but was not preferentially labeled in the mutant. Over 24 h, PM label intensity increased to that of ER in both cell lines. However, NM activity diminished in HSDM1C1 cells by 24 h to a small fraction of that in ER. In response to agonists, HSDM1C1 cells release labeled arachidonate for eicosanoid synthesis most readily when they have been labeled for short times. Our results therefore suggest that NM and ER, sites of cyclooxygenase in murine fibroblasts, are probably sources for release of [3H]arachidonate, whereas PM and mitochondria are unlikely to be major sources of eicosanoid precursors. PMID:3926781

Strengthening health data on a rare and heterogeneous disease: sarcoma incidence and histological subtypes in Germany.

PubMed

Ressing, Meike; Wardelmann, Eva; Hohenberger, Peter; Jakob, Jens; Kasper, Bernd; Emrich, Katharina; Eberle, Andrea; Blettner, Maria; Zeissig, Sylke Ruth

2018-02-12

The population-based incidence of sarcoma and its histological subtypes in Germany is unknown. Up-to-date information on a disease with an incidence comparable to other cancer entities is of high public health relevance. The aim of this study was to determine this incidence and to detect significant changes in incidence trends using data from German epidemiological cancer registries. Pooled data from the German Centre for Cancer Registry Data with a primary diagnosis occurring in 2013 were used. To date, this is the latest data on cancer incidence available for Germany. All German cancer registries with sufficient completeness were included (10 out of 11), covering a population of 70.0 million people, representing 87% of the German population. All malignant sarcomas according to the RARECARE Project and the WHO classification 2002 were considered for analysis and, above all, gastrointestinal stromal tumours (GIST) of uncertain behaviour. Sensitivity analysis was performed excluding certain histologies. The analysis included 3404 cases in men and 3442 cases in women diagnosed in 2013. The age adjusted sarcoma incidence (European standard) was 7.4 (men) and 6.6 (women) per 100,000 inhabitants. About 70% of sarcomas were soft tissue sarcomas, about 22% GIST, and about 9% bone sarcomas. The most common histological subtypes besides GIST were fibrosarcomas (14%) and liposarcomas (12%) in men and complex mixed and stromal neoplasms (22%), non-uterine leiomysarcomas (10%) and fibrosarcomas (9%) in women. Considering the trend for the years of diagnosis 2004 to 2013, there was a significant increase in incidence for GIST while the incidence of soft tissue sarcomas (only men) as well as of bone sarcoma stayed constant over time. As to soft tissue sarcoma in women, the incidence stayed constant up to the year 2009 and significantly decreased afterwards. This study is the first detailed analysis of a German-wide population-based sarcoma incidence showing results comparable to the incidence detected in the RARECARE Project.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pang, Xiaojuan; Shu, Yuxin; Niu, Zhiyuan

Post-translational regulation plays a critical role in the control of cell growth and proliferation. The phosphorylation of peroxisome proliferator-activated receptor γ (PPARγ) is the most important post-translational modification. The function of PPARγ phosphorylation has been studied extensively in the past. However, the relationship between phosphorylated PPARγ1 and tumors remains unclear. Here we investigated the role of PPARγ1 phosphorylation in human fibrosarcoma HT1080 cell line. Using the nonphosphorylation (Ser84 to alanine, S84A) and phosphorylation (Ser84 to aspartic acid, S84D) mutant of PPARγ1, the results suggested that phosphorylation attenuated PPARγ1 transcriptional activity. Meanwhile, we demonstrated that phosphorylated PPARγ1 promoted HT1080 cell proliferationmore » and this effect was dependent on the regulation of cell cycle arrest. The mRNA levels of cyclin-dependent kinase inhibitor (CKI) p21{sup Waf1/Cip1} and p27{sup Kip1} descended in PPARγ1{sup S84D} stable HT1080 cell, whereas the expression of p18{sup INK4C} was not changed. Moreover, compared to the PPARγ1{sup S84A}, PPARγ1{sup S84D} up-regulated the expression levels of cyclin D1 and cyclin A. Finally, PPARγ1 phosphorylation reduced sensitivity to agonist rosiglitazone and increased resistance to anticancer drug 5-fluorouracil (5-FU) in HT1080 cell. Our findings establish PPARγ1 phosphorylation as a critical event in human fibrosarcoma growth. These findings raise the possibility that chemical compounds that prevent the phosphorylation of PPARγ1 could act as anticancer drugs. - Highlights: • Phosphorylation attenuates PPARγ1 transcriptional activity. • Phosphorylated PPARγ1 promotes HT1080 cells proliferation. • PPARγ1 phosphorylation regulates cell cycle by mediating expression of cell cycle regulators. • PPARγ1 phosphorylation reduces sensitivity to agonist and anticancer drug. • Our findings establish PPARγ1 phosphorylation as a critical event in HT1080 cells growth.« less

Androgen-Induced Cell Migration: Role of Androgen Receptor/Filamin A Association

PubMed Central

Castoria, Gabriella; D'Amato, Loredana; Ciociola, Alessandra; Giovannelli, Pia; Giraldi, Tiziana; Sepe, Leandra; Paolella, Giovanni; Barone, Maria Vittoria; Migliaccio, Antimo; Auricchio, Ferdinando

2011-01-01

Background Androgen receptor (AR) controls male morphogenesis, gametogenesis and prostate growth as well as development of prostate cancer. These findings support a role for AR in cell migration and invasiveness. However, the molecular mechanism involved in AR-mediated cell migration still remains elusive. Methodology/Principal Findings Mouse embryo NIH3T3 fibroblasts and highly metastatic human fibrosarcoma HT1080 cells harbor low levels of transcriptionally incompetent AR. We now report that, through extra nuclear action, AR triggers migration of both cell types upon stimulation with physiological concentrations of the androgen R1881. We analyzed the initial events leading to androgen-induced cell migration and observed that challenging NIH3T3 cells with 10 nM R1881 rapidly induces interaction of AR with filamin A (FlnA) at cytoskeleton. AR/FlnA complex recruits integrin beta 1, thus activating its dependent cascade. Silencing of AR, FlnA and integrin beta 1 shows that this ternary complex controls focal adhesion kinase (FAK), paxillin and Rac, thereby driving cell migration. FAK-null fibroblasts migrate poorly and Rac inhibition by EHT impairs motility of androgen-treated NIH3T3 cells. Interestingly, FAK and Rac activation by androgens are independent of each other. Findings in human fibrosarcoma HT1080 cells strengthen the role of Rac in androgen signaling. The Rac inhibitor significantly impairs androgen-induced migration in these cells. A mutant AR, deleted of the sequence interacting with FlnA, fails to mediate FAK activation and paxillin tyrosine phosphorylation in androgen-stimulated cells, further reinforcing the role of AR/FlnA interaction in androgen-mediated motility. Conclusions/Significance The present report, for the first time, indicates that the extra nuclear AR/FlnA/integrin beta 1 complex is the key by which androgen activates signaling leading to cell migration. Assembly of this ternary complex may control organ development and prostate cancer metastasis. PMID:21359179

Piroxicam, indomethacin and aspirin action on a murine fibrosarcoma. Effects on tumour-associated and peritoneal macrophages.

PubMed Central

Valdéz, J C; Perdigón, G

1991-01-01

Growth of a methylcholanthrene-induced fibrosarcoma in BALB/c mice was accompanied by an increase in the activation state of tumour-associated macrophages (TAM), as measured by their FcIgG receptor expression, phagocytic index and beta-glucuronidase levels. All of these parameters were markedly higher in TAM than in peritoneal macrophages (PM) derived from the same animal. On the other hand, PM from tumour-bearing mice showed lower activation parameters than PM from normal animals. We also studied the effect on tumour development of three inhibitors of prostaglandin synthesis: indomethacin, piroxicam and aspirin. Intraperitoneal administration of these drugs during 8 d was followed by the regression of palpable tumours. Indomethacin (90 mg/d) induced 45% regression, while with piroxicam (two 400 mg/d doses and six 200 mg/d doses) and aspirin (1 mg/d) 32% and 30% regressions, respectively, were observed. The growth rate of nonregressing tumours, which had reached different volumes by the end of the treatment, was delayed to a similar extent by the three anti-inflammatory non-steroidal drugs (NSAID). With respect to TAM, the treatment did not induce any significant change in their activation state, though both piroxicam and indomethacin increased slightly the TAM number. In contrast, NSAID administration was followed by a remarkable increase in the activation parameters of PM when compared with PM from tumour-bearing mice receiving no treatment. Indeed, these parameters were in some cases higher than those of PM from normal mice. The leukocytosis (60,000/microliters) with neutrophilia (80%) induced by tumour growth on peripheral blood leukocytes (PBL) was reversed by the treatment to values close to normal, in parallel with the reduction of tumour size. A drop in haematocrit was also noted which was most probably a consequence of tumour growth rather than of the treatment. This study reveals that the three NSAID tested have a remarkable antitumour activity, which correlates with the restoration of PM activity and PBL values. PMID:1834380

Reversible pulmonary hypertension in a cat.

PubMed

Baron Toaldo, M; Guglielmini, C; Diana, A; Giunti, M; Dondi, F; Cipone, M

2011-05-01

A 13-year-old, neutered female domestic shorthair cat was presented for sudden respiratory distress following palliative radiotherapy and the combined administration of a single dose of carboplatin for the treatment of recurrent fibrosarcoma. Clinical and radiographic findings were suggestive of pleural effusion. Echocardiography revealed marked right-sided cardiac enlargement associated with tricuspid regurgitation and Doppler evidence of pulmonary hypertension. After 25 days of treatment for congestive heart failure and suspected pulmonary thromboembolism, clinical signs and echocardiographic and Doppler evidence of right-sided cardiac enlargement and pulmonary hypertension had completely resolved. To the best of the authors' knowledge, this is the first report of reversible pulmonary hypertension, likely secondary to pulmonary thromboembolism, in a cat. © 2011 British Small Animal Veterinary Association.

Non-Mulberry and Mulberry Silk Protein Sericins as Potential Media Supplement for Animal Cell Culture.

PubMed

Sahu, Neety; Pal, Shilpa; Sapru, Sunaina; Kundu, Joydip; Talukdar, Sarmistha; Singh, N Ibotambi; Yao, Juming; Kundu, Subhas C

2016-01-01

Silk protein sericins, in the recent years, find application in cosmetics and pharmaceuticals and as biomaterials. We investigate the potential of sericin, extracted from both mulberry Bombyx mori and different non-mulberry sources, namely, tropical tasar, Antheraea mylitta; muga, Antheraea assama; and eri, Samia ricini, as growth supplement in serum-free culture medium. Sericin supplemented media containing different concentrations of sericins from the different species are examined for attachment, growth, proliferation, and morphology of fibrosarcoma cells. The optimum sericin supplementation seems to vary with the source of sericins. The results indicate that all the sericins promote the growth of L929 cells in serum-free culture media; however, S. ricini sericin seems to promote better growth of cells amongst other non-mulberry sericins.

Non-Mulberry and Mulberry Silk Protein Sericins as Potential Media Supplement for Animal Cell Culture

PubMed Central

Sahu, Neety; Pal, Shilpa; Sapru, Sunaina; Kundu, Joydip; Talukdar, Sarmistha; Singh, N. Ibotambi; Yao, Juming

2016-01-01

Silk protein sericins, in the recent years, find application in cosmetics and pharmaceuticals and as biomaterials. We investigate the potential of sericin, extracted from both mulberry Bombyx mori and different non-mulberry sources, namely, tropical tasar, Antheraea mylitta; muga, Antheraea assama; and eri, Samia ricini, as growth supplement in serum-free culture medium. Sericin supplemented media containing different concentrations of sericins from the different species are examined for attachment, growth, proliferation, and morphology of fibrosarcoma cells. The optimum sericin supplementation seems to vary with the source of sericins. The results indicate that all the sericins promote the growth of L929 cells in serum-free culture media; however, S. ricini sericin seems to promote better growth of cells amongst other non-mulberry sericins. PMID:27517047

Prognosis after surgical excision of canine fibrous connective tissue sarcomas.

PubMed

Bostock, D E; Dye, M T

1980-09-01

One hundred eighty seven dogs from which fibrous connective tissue sarcomas had been excised were studied until death or for at least 3 years after surgery. Dogs with a skin fibrosarcoma had a median survival time of 80 weeks, compared with 140 weeks for animals with haemangiopericytoma in similar sites, this difference being statistically significant. However, the difference in survival time between the two histologic types disappeared when tumours with a similar mitotic index were compared. Dogs with a tumour of mitotic index 9 or more had a median survival time of 49 weeks, compared with 118 weeks for those with a tumour of mitotic index less than 9, regardless of tumour morphology. Tumour recurrence rates of 62% and 25% respectively for the two groups were also significantly different.

Tumor Response to Radiotherapy Regulated by Endothelial Cell Apoptosis

NASA Astrophysics Data System (ADS)

Garcia-Barros, Monica; Paris, Francois; Cordon-Cardo, Carlos; Lyden, David; Rafii, Shahin; Haimovitz-Friedman, Adriana; Fuks, Zvi; Kolesnick, Richard

2003-05-01

About 50% of cancer patients receive radiation therapy. Here we investigated the hypothesis that tumor response to radiation is determined not only by tumor cell phenotype but also by microvascular sensitivity. MCA/129 fibrosarcomas and B16F1 melanomas grown in apoptosis-resistant acid sphingomyelinase (asmase)-deficient or Bax-deficient mice displayed markedly reduced baseline microvascular endothelial apoptosis and grew 200 to 400% faster than tumors on wild-type microvasculature. Thus, endothelial apoptosis is a homeostatic factor regulating angiogenesis-dependent tumor growth. Moreover, these tumors exhibited reduced endothelial apoptosis upon irradiation and, unlike tumors in wild-type mice, they were resistant to single-dose radiation up to 20 grays (Gy). These studies indicate that microvascular damage regulates tumor cell response to radiation at the clinically relevant dose range.

In situ method for estimating cell survival in a solid tumor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Alfieri, A.A.; Hahn, E.W.

1978-09-01

The response of the murine Meth-A fibrosarcoma to single and fractionated doses of x-irradiation, actinomycin D chemotherapy, and/or concomitant local tumor hyperthermia was assayed with the use of an in situ method for estimating cell kill within a solid tumor. The cell survival assay was based on a standard curve plotting number of inoculated viable cells with and without radiation-inactivated homologous tumor cells versus the time required for i.m. tumors to grow to 1.0 cu cm. The time for post-treatment tumors to grow to 1.0 cu cm was cross-referenced to the standard curve, and the number of surviving cells contributingmore » to tumor regrowth was estimated. The resulting surviving fraction curves closely resemble those obtained with in vitro systems.« less

Electrochemotherapy-induced radiation recall in a cat.

PubMed

Spugnini, Enrico P; Dotsinsky, Ivan; Mudrov, Nikolay; Citro, Gennaro; Caruso, Giovanni; Cardelli, Pierluigi; Baldi, Alfonso

2008-01-01

Electrochemotherapy is gaining popularity for the treatment of malignancies of companion animals due to its efficacy and low cost. In this paper, we describe the successful treatment of a recurring fibrosarcoma in a cat by using cisplatin selectively driven within the tumor cells by trains of biphasic pulses. The cat's tumor did not recur over the following five months, however the cat did experience severe erythema at the site of previous irradiation, followed by moist desquamation and ulcer that required debridement and prolonged therapy with steroids and antihistaminic drugs. The symptoms and the response to symptomatic therapy were strongly suggestive of radiation recall. Electrochemotherapy (ECT) should be used with caution in previously irradiated areas. Further studies are warranted in this field due to its potential as a rescue for relapsing tumors.

Mutant IDH1 is required for IDH1 mutated tumor cell growth

PubMed Central

Jin, Genglin; Pirozzi, Christopher J.; Chen, Lee H.; Lopez, Giselle Y.; Duncan, Christopher G.; Feng, Jie; Spasojevic, Ivan; Bigner, Darell D.; He, Yiping; Yan, Hai

2012-01-01

Frequent somatic hotspot mutations in isocitrate dehydrogenase 1 (IDH1) have been identified in gliomas, acute myeloid leukemias, chondrosarcomas, and other cancers, providing a likely avenue for targeted cancer therapy. However, whether mutant IDH1 protein is required for maintaining IDH1 mutated tumor cell growth remains unknown. Here, using a genetically engineered inducible system, we report that selective suppression of endogenous mutant IDH1 expression in HT1080, a fibrosarcoma cell line with a native IDH1R132C heterozygous mutation, significantly inhibits cell proliferation and decreases clonogenic potential. Our findings offer insights into changes that may contribute to the inhibition of cell proliferation and offer a strong preclinical rationale for utilizing mutant IDH1 as a valid therapeutic target. PMID:22885298

4F2 monoclonal antibody recognizes a surface antigen on spread human fibroblasts of embryonic but not of adult origin

PubMed Central

1984-01-01

The 4F2 monoclonal antibody (mAb) has been shown to recognize a 120- kilodalton glycoprotein expressed on the cell surface of human peripheral blood monocytes, activated (but not resting) T or B cells, and T and B lymphoblastoid cell lines. In this report we show that 4F2 mAb specifically binds to the surface of adherent human embryonic fibroblasts but fails to bind to normal adult fibroblasts. Moreover, 4F2 antigen was expressed on sarcoma-derived or SV40-transformed adult fibroblastic cells. Finally, addition of 4F2 mAb inhibited the growth of cultured HT-1080 fibrosarcoma cell line, but had no inhibitory effect on various embryonic and adult normal or transformed fibroblasts. PMID:6538202

In vitro anticancer effects of a RAGE inhibitor discovered using a structure-based drug design system

PubMed Central

El-Far, Ali Hafez Ali Mohammed; Munesue, Seiichi; Harashima, Ai; Sato, Akira; Shindo, Mika; Nakajima, Shingo; Inada, Mana; Tanaka, Mariko; Takeuchi, Akihiko; Tsuchiya, Hiroyuki; Yamamoto, Hiroshi; Shaheen, Hazem M.E.; El-Sayed, Yasser S.; Kawano, Shuhei; Tanuma, Sei-Ichi; Yamamoto, Yasuhiko

2018-01-01

Receptor for advanced glycation end-products (RAGE) is a pattern recognition receptor implicated in the pathogenesis of certain types of cancer. In the present study, papaverine was identified as a RAGE inhibitor using the conversion to small molecules through optimized-peptide strategy drug design system. Papaverine significantly inhibited RAGE-dependent nuclear factor κ-B activation driven by high mobility group box-1, a RAGE ligand. Using RAGE- or dominant-negative RAGE-expressing HT1080 human fibrosarcoma cells, the present study revealed that papaverine suppressed RAGE-dependent cell proliferation and migration dose-dependently. Furthermore, papaverine significantly inhibited cell invasion. The results of the present study suggested that papaverine could inhibit RAGE, and provided novel insights into the field of RAGE biology, particularly anticancer therapies. PMID:29541234

Antioxidant Effect of Berberine and its Phenolic Derivatives Against Human Fibrosarcoma Cells.

PubMed

Pongkittiphan, Veerachai; Chavasiri, Warinthorn; Supabphol, Roongtawan

2015-01-01

Berberine (B1), isolated from stems of Coscinium fenestratum (Goetgh.) Colebr, was used as a principle structure to synthesize three phenolic derivatives: berberrubine (B2) with a single phenolic group, berberrubine chloride (B3) as a chloride counter ion derivative, and 2,3,9,10-tetra-hydroxyberberine chloride (B4) with four phenolic groups, to investigate their direct and indirect antioxidant activities. For DPPH assay, compounds B4, B3, and B2 showed good direct antioxidant activity (IC50 values=10.7±1.76, 55.2±2.24, and 87.4±6.65 μM, respectively) whereas the IC50 value of berberine was higher than 500 μM. Moreover, compound B4 exhibited a better DPPH scavenging activity than BHT as a standard antioxidant (IC50=72.7±7.22 μM) due to the ortho position of hydroxyl groups and its capacity to undergo intramolecular hydrogen bonding. For cytotoxicity assay against human fibrosarcoma cells (HT1080) using MTT reagent, the sequence of IC50 value at 7-day treatment stated that B1

Biocompatibility and therapeutic evaluation of magnetic liposomes designed for self-controlled cancer hyperthermia and chemotherapy.

PubMed

Gogoi, Manashjit; Jaiswal, Manish K; Sarma, Haladhar Dev; Bahadur, Dhirendra; Banerjee, Rinti

2017-06-19

Magnetic liposome-mediated combined chemotherapy and hyperthermia is gaining importance as an effective therapeutic modality for cancer. However, control and maintenance of optimum hyperthermia are major challenges in clinical settings due to the overheating of tissues. To overcome this problem, we developed a novel magnetic liposomes formulation co-entrapping a dextran coated biphasic suspension of La 0.75 Sr 0.25 MnO 3 (LSMO) and iron oxide (Fe 3 O 4 ) nanoparticles for self-controlled hyperthermia and chemotherapy. However, the general apprehension about biocompatibility and safety of the newly developed formulation needs to be addressed. In this work, in vitro and in vivo biocompatibility and therapeutic evaluation studies of the novel magnetic liposomes are reported. Biocompatibility study of the magnetic liposomes formulation was carried out to evaluate the signs of preliminary systemic toxicity, if any, following intravenous administration of the magnetic liposomes in Swiss mice. Therapeutic efficacy of the magnetic liposomes formulation was evaluated in the fibrosarcoma tumour bearing mouse model. Fibrosarcoma tumour-bearing mice were subjected to hyperthermia following intratumoral injection of single or double doses of the magnetic liposomes with or without chemotherapeutic drug paclitaxel. Hyperthermia (three spurts, each at 3 days interval) with drug loaded magnetic liposomes following single dose administration reduced the growth of tumours by 2.5 fold (mean tumour volume 2356 ± 550 mm 3 ) whereas the double dose treatment reduced the tumour growth by 3.6 fold (mean tumour volume 1045 ± 440 mm 3 ) compared to their corresponding control (mean tumour volume 3782 ± 515 mm 3 ). At the end of the tumour efficacy studies, the presence of MNPs was studied in the remnant tumour tissues and vital organs of the mice. No significant leaching or drainage of the magnetic liposomes during the study was observed from the tumour site to the other vital organs of the body, suggesting again the potential of the novel magnetic liposomes formulation for possibility of developing as an effective modality for treatment of drug resistant or physiologically vulnerable cancer.

Molecular targets and signaling pathways regulated by nuclear translocation of syndecan-1.

PubMed

Szatmári, Tünde; Mundt, Filip; Kumar-Singh, Ashish; Möbus, Lena; Ötvös, Rita; Hjerpe, Anders; Dobra, Katalin

2017-12-08

The cell-surface heparan sulfate proteoglycan syndecan-1 is important for tumor cell proliferation, migration, and cell cycle regulation in a broad spectrum of malignancies. Syndecan-1, however, also translocates to the cell nucleus, where it might regulate various molecular functions. We used a fibrosarcoma model to dissect the functions of syndecan-1 related to the nucleus and separate them from functions related to the cell-surface. Nuclear translocation of syndecan-1 hampered the proliferation of fibrosarcoma cells compared to the mutant lacking nuclear localization signal. The growth inhibitory effect of nuclear syndecan-1 was accompanied by significant accumulation of cells in the G0/G1 phase, which indicated a possible G1/S phase arrest. We implemented multiple, unsupervised global transcriptome and proteome profiling approaches and combined them with functional assays to disclose the molecular mechanisms that governed nuclear translocation and its related functions. We identified genes and pathways related to the nuclear compartment with network enrichment analysis of the transcriptome and proteome. The TGF-β pathway was activated by nuclear syndecan-1, and three genes were significantly altered with the deletion of nuclear localization signal: EGR-1 (early growth response 1), NEK11 (never-in-mitosis gene a-related kinase 11), and DOCK8 (dedicator of cytokinesis 8). These candidate genes were coupled to growth and cell-cycle regulation. Nuclear translocation of syndecan-1 influenced the activity of several other transcription factors, including E2F, NFκβ, and OCT-1. The transcripts and proteins affected by syndecan-1 showed a striking overlap in their corresponding biological processes. These processes were dominated by protein phosphorylation and post-translation modifications, indicative of alterations in intracellular signaling. In addition, we identified molecules involved in the known functions of syndecan-1, including extracellular matrix organization and transmembrane transport. Collectively, abrogation of nuclear translocation of syndecan-1 resulted in a set of changes clustering in distinct patterns, which highlighted the functional importance of nuclear syndecan-1 in hampering cell proliferation and the cell cycle. This study emphasizes the importance of the localization of syndecan-1 when considering its effects on tumor cell fate.

Effects of synthetic sphingosine-1-phosphate analogs on cytosolic phospholipase A2alpha-independent release of arachidonic acid and cell toxicity in L929 fibrosarcoma cells: the structure-activity relationship.

PubMed

Shimizu, Masaya; Muramatsu, Yuki; Tada, Eiko; Kurosawa, Takeshi; Yamaura, Erika; Nakamura, Hiroyuki; Fujino, Hiromichi; Houjyo, Yuuya; Miyasaka, Yuri; Koide, Yuuki; Nishida, Atsushi; Murayama, Toshihiko

2009-03-01

Sphingolipid metabolites including ceramide, sphingosine, and their phosphorylated products [sphingosine-1-phosphate (S1P) and ceramide-1-phosphate] regulate cell functions including arachidonic acid (AA) metabolism and cell death. The development of analogs of S1P may be useful for regulating these mediator-induced cellular responses. We synthesized new analogs of S1P and examined their effects on the release of AA and cell death in L929 mouse fibrosarcoma cells. Among the analogs tested, several compounds including DMB-mC11S [dimethyl (2S,3R)-2-tert-butoxycarbonylamino-3-hydroxy-3-(3'-undecyl)phenylpropyl phosphate] and DMB-mC9S [dimethyl (2S,3R)-2-tert-butoxycarbonylamino-3-hydroxy-3-(3'-nonyl)phenylpropyl phosphate] released AA within 1 h and caused cell death 6 h after treatment. The release of AA was observed in C12 cells [a L929 variant lacking a type alpha cytosolic phospholipase A(2) (cPLA(2)alpha)] and L929-cPLAalpha-siRNA cells (L929 cells treated with small interference RNA for cPLA(2)alpha). Treatment with pharmacological inhibitors of secretory and Ca(2+)-independent PLA(2)s decreased the DMB-mC11S-induced release of AA. The effect of the S1P analogs tested on the release of AA was comparable to that on cell death in L929 cells, and a high correlation coefficient was observed. Two analogs lacking a butoxycarbonyl moiety [DMAc-mC11S (dimethyl (2S,3R)-2-acetamino-3-hydroxy-3-(3'-undecyl)phenylpropyl phosphate] and DMAm-mC11S [dimethyl (2S,3R)-2-amino-3-hydroxy-3-(3'-undecyl)phenylpropyl phosphate)] had inhibitory effects on the release of AA and cell toxicity induced by DMB-mC11S. Synthetic phosphorylated lipid analogs may be useful for studying PLA(2) activity and its toxicity in cells. [Supplementary Fig. 1: available only at http://dx.doi.org/10.1254/jphs.08284FP].

3-(3-Hydroxy-4-methoxyphenyl)-4-(3,4,5-trimethoxyphenyl)-1,2,5-selenadiazole (G-1103), a novel combretastatin A-4 analog, induces G2/M arrest and apoptosis by disrupting tubulin polymerization in human cervical HeLa cells and fibrosarcoma HT-1080 cells.

PubMed

Zuo, Daiying; Guo, Dandan; Jiang, Xuewei; Guan, Qi; Qi, Huan; Xu, Jingwen; Li, Zengqiang; Yang, Fushan; Zhang, Weige; Wu, Yingliang

2015-02-05

Microtubule is a popular target for anticancer drugs. In this study, we describe the effect 3-(3-hydroxy-4-methoxyphenyl)-4-(3,4,5-trimethoxyphenyl)-1,2,5-selenadiazole (G-1103), a newly synthesized analog of combretastatin A-4 (CA-4), showing a strong time- and dose-dependent anti-proliferative effect on human cervical cancer HeLa cells and human fibrosarcoma HT-1080 cells. We demonstrated that the growth inhibitory effects of G-1103 in HeLa and HT-1080 cells were associated with microtubule depolymerization and proved that G-1103 acted as microtubule destabilizing agent. Furthermore, cell cycle analysis revealed that G-1103 treatment resulted in cell cycle arrest at the G2/M phase in a time-dependent manner with subsequent apoptosis induction. Western blot analysis revealed that down-regulation of cdc25c and up-regulation of cyclin B1 was related with G2/M arrest in HeLa and HT-1080 cells treatment with G-1103. In addition, G-1103 induced HeLa cell apoptosis by up-regulating cleaved caspase-3, Fas, cleaved caspase-8 expression, which indicated that G-1103 induced HeLa cell apoptosis was mainly associated with death receptor pathway. However, G-1103 induced HT-1080 cell apoptosis by up-regulating cleaved caspase-3, Fas, cleaved caspase-8, Bax and cleaved caspase-9 expression and down-regulating anti-apoptotic protein Bcl-2 expression, which indicated that G-1103 induced HT-1080 cell apoptosis was associated with both mitochondrial and death receptor pathway. Taken together, all the data demonstrated that G-1103 exhibited its antitumor activity through disrupting the microtubule assembly, causing cell cycle arrest and consequently inducing apoptosis in HeLa and HT-1080 cells. Therefore, the novel compound G-1103 is a promising microtubule inhibitor that has great potentials for therapeutic treatment of various malignancies. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Vismodegib and Gamma-Secretase/Notch Signalling Pathway Inhibitor RO4929097 in Treating Patients With Advanced or Metastatic Sarcoma

ClinicalTrials.gov

2016-06-09

Adult Alveolar Soft Part Sarcoma; Adult Angiosarcoma; Adult Desmoplastic Small Round Cell Tumor; Adult Epithelioid Hemangioendothelioma; Adult Epithelioid Sarcoma; Adult Extraskeletal Myxoid Chondrosarcoma; Adult Extraskeletal Osteosarcoma; Adult Fibrosarcoma; Adult Leiomyosarcoma; Adult Liposarcoma; Adult Malignant Mesenchymoma; Adult Malignant Peripheral Nerve Sheath Tumor; Adult Rhabdomyosarcoma; Adult Synovial Sarcoma; Adult Unclassified Pleomorphic Sarcoma; Chondrosarcoma; Clear Cell Sarcoma of the Kidney; Conjunctival Kaposi Sarcoma; Dermatofibrosarcoma Protuberans; Gastrointestinal Stromal Tumor; Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Metastatic Osteosarcoma; Ovarian Sarcoma; Recurrent Adult Soft Tissue Sarcoma; Recurrent Adult Unclassified Pleomorphic Sarcoma of Bone; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Kaposi Sarcoma; Recurrent Osteosarcoma; Recurrent Uterine Corpus Sarcoma; Small Intestine Leiomyosarcoma; Stage III Adult Soft Tissue Sarcoma; Stage III Uterine Sarcoma; Stage IV Adult Soft Tissue Sarcoma; Stage IV Uterine Sarcoma; Unclassified Pleomorphic Sarcoma of Bone

Anti-tumour potential of a gallic acid-containing phenolic fraction from Oenothera biennis.

PubMed

Pellegrina, Chiara Dalla; Padovani, Giorgia; Mainente, Federica; Zoccatelli, Gianni; Bissoli, Gaetano; Mosconi, Silvia; Veneri, Gianluca; Peruffo, Angelo; Andrighetto, Giancarlo; Rizzi, Corrado; Chignola, Roberto

2005-08-08

A phenolic fraction purified form defatted seeds of Oenothera biennis promoted selective apoptosis of human and mouse bone marrow-derived cell lines following first-order kinetics through a caspase-dependent pathway. In non-leukemia tumour cell lines, such as human colon carcinoma CaCo(2) cells and mouse fibrosarcoma WEHI164 cells, this fraction inhibited (3)H-thymidine incorporation but not cell death or cell cycle arrest. Human peripheral blood mononuclear cells showed low sensitivity to treatment. Single bolus injection of the phenolic fraction could delay the growth of established myeloma tumours in syngeneic animals. HPLC and mass spectrometry analysis revealed that the fraction contains gallic acid. However, the biological activity of the fraction differs from the activity of this phenol and hence it should be attributed to other co-purified molecules which remain still unidentified.

Nodular presentation of Dirofilaria repens infection in a cat mimicking a fibrosarcoma.

PubMed

Manzocchi, Simone; Lendner, Matthias; Piseddu, Eleonora; Sebastiani, Valeria; Morabito, Simona; Daugschies, Arwid; Pantchev, Nikola

2017-03-01

A cat with multiple subcutaneous nodules suggesting a soft tissue sarcoma by physical and computed tomographic examination was diagnosed as being affected by subcutaneous filariosis based on cytologic and ultrasonographic assessments. Nodules were surgically removed and extracted nematodes were identified by PCR as Dirofilaria repens. Furthermore, DNA of Dipetalonema dracunculoides (syn. Acantocheilonema dracunculoides) was detected by PCR, with no evidence of circulating microfilariae. To the best of the authors' knowledge, this represents the first report describing adults of D repens in multiple subcutaneous nodules in a cat. Cytopathologic examination allowed characterization of the parasitic nature of the nodules. Veterinary practitioners should be aware of the possible nodular presentation of D repens in cats and should include D repens in the differential diagnosis of subcutaneous neoformations in the cat. © 2016 American Society for Veterinary Clinical Pathology.

Bilateral rostral maxillectomy and nasal planectomy for large rostral maxillofacial neoplasms in six dogs and one cat.

PubMed

Lascelles, B Duncan X; Henderson, Ralph A; Seguin, Bernard; Liptak, Julius M; Withrow, Stephen J

2004-01-01

This paper describes in detail an aggressive rostral maxillectomy procedure in one cat and six dogs, and the postoperative complications and outcomes are reported. The surgeries were performed to attempt complete excision of large and extensive rostral maxillary fibrosarcomas (n=4), squamous cell carcinomas (n=2), or poorly differentiated mesenchymal neoplasia (n=1). The surgeries involved transection of the maxilla at the level of premolar (PM)1 and PM2 in a cat and two dogs, and between PM2 and PM3 in four dogs. There were no intraoperative complications. Complete margins of resection were obtained in all cases. The postoperative appearance was acceptable to owners. Local recurrence was only observed in one dog (10 months after surgery) during a follow-up period of 11 to 66 months (median, 21.5 months).

Hematological toxicity and therapeutic efficacy of lomustine in 20 tumor-bearing cats: critical assessment of a practical dosing regimen.

PubMed

Fan, Timothy M; Kitchell, Barbara E; Dhaliwal, Ravinder S; Jones, Pamela D; Hintermeister, John G; Paria, Biman C

2002-01-01

Twenty cats with spontaneously arising tumors received oral lomustine at a dose range of 32 to 59 mg/m2 every 21 days. Due to biohazard concerns associated with lomustine capsule reformulation, a standardized 10-mg capsule dosage was used for all cats regardless of body weight. Severe hematological toxicity was infrequent, with the incidence of either grade III or IV neutropenia and thrombocytopenia being 4.1% and 1.0%, respectively. Cats receiving higher cumulative doses of lomustine trended toward a greater likelihood for progressive neutropenia (P=0.07). Two cats with lymphoma, two cats with fibrosarcoma, and one cat with multiple myeloma achieved a measurable partial response to lomustine therapy. Cats treated with higher dosages of lomustine trended toward statistically significant higher response rates (P=0.07).

Sinonasal inflammatory myofibroblastic pseudotumor (plasma cell granuloma).

PubMed

Arpacı, Rabia Bozdoğan; Kara, Tuba; Özyedek, Esen; Serinsöz, Ebru; Vayısoğlu, Yusuf; Özgür, Anıl; Arpacı, Taner; Özcan, Cengiz

2015-01-01

Inflammatory myofibroblastic pseudotumor (plasma cell granuloma) is a soft tissue lesion consisting of myofibroblasts, mature lymphocytes, histiocytes, plasma cells, eosinophils, and extracellular collagen. Various sites in the body may harbor these lesions. Lungs, omentum, intestines, mesentery, and urinary system are the most susceptible areas. It is usually seen in children and young adults. The lesion is rarely detected in the head and neck region. The orbit and the upper respiratory system are the most common localizations in the head and neck region. Sinonasal tract is a rare site of involvement. The differential diagnosis includes squamous cell carcinoma (spindle cell variant), inflammatory fibrosarcoma, leiomyosarcoma, schwannoma, and nonspecific inflammation. Our patient who had a sinonasal mass showed a benign tumor consisting of spindle tumor cells and inflammatory cells histopathologically. This case was presented due to its rare existence to this site.

Dedifferentiated liposarcoma of the spermatic cord with a hemangioendothelioma-like component: a case report and review of the literature.

PubMed

Okano, Shinji; Yamamoto, Hidetaka; Kono, Shinji; Fujii, Hiroshi; Shirabe, Ken; Maehara, Yoshihiko; Oda, Yoshinao

2013-09-01

Atypical lipomatous tumor or well-differentiated liposarcoma/dedifferentiated liposarcoma (DDLPS) is the most frequent subtype of malignant adipocytic tumor. This tumor typically presents in late adult life, most commonly in the retroperitoneum, extremities, or spermatic cord. It has been reported that the dedifferentiated component consists mainly of high-grade sarcoma, including undifferentiated pleomorphic sarcoma, fibrosarcoma, and myxofibrosarcoma, and it has been recently reported that the dedifferentiated component can be also made up of a low-grade sarcomatous component. Therefore, the dedifferentiated areas exhibit a wide morphological spectrum that commonly includes fibroblastic/myofibroblastic and fibrohistiocytic tumors but very rarely includes vascular tumors. We present here the first reported case of DDLPS with a hemangioendothelioma-like component in the spermatic cord. Copyright © 2013 Elsevier GmbH. All rights reserved.

Pulmonary blastoma with diverse mesenchymal proliferation

PubMed Central

Chaudhuri, M. Ray; Eastham, W. N.; Fredriksz, P. A.

1972-01-01

Pulmonary blastomas are extremely rare subpleural tumours consisting of relatively well-differentiated branched tubular glands which resemble fetal lung tissue embedded in a malignant mesodermal stroma. The previous 13 established cases reported up to June 1969 are now supplemented by a fourteenth. The patient was a 32-year-old man who developed acute pain in the right chest followed by a haemorrhagic pleural effusion. At thoracotomy a yellowish-white necrotic and vascular tumour was located lying loosely in the fissure between the upper and the middle lobes. The histological appearance of the tumour was unusual in that the mesodermal element was very variable and in different areas simulated fibrosarcoma, leiomyosarcoma, lipomyxosarcoma, and malignant haemangiopericytoma. This diversity of mesodermal proliferation is best explained on the basis that the tumour has originated in an embryonic or pleuripotential type of mesenchyme, the site of which is probably in the periphery of the lung. Images PMID:5075621

Fine needle aspiration (FNA) of synovial sarcoma--a comparative histological-cytological study of 15 cases, including immunohistochemical, electron microscopic and cytogenetic examination and DNA-ploidy analysis.

PubMed

Akerman, M; Willén, H; Carlén, B; Mandahl, N; Mertens, F

1996-06-01

A retrospective study of 25 FNAs (11 aspirates from primary tumours and 14 from recurrencies and metastases) from 15 synovial sarcomas was performed. The cytological findings were correlated with the histopathology and the value of immunohistochemical and electron microscopic examination as well as DNA-ploidy and cytogenetic analysis for diagnosis were assessed. A reproducible cellular pattern with a reliable diagnosis of spindle cell sarcoma was possible provided that the aspirates were cell rich. However, a true biphasic pattern indicative of synovial sarcoma was only seen in one of the 25 specimens. Electron microscopic examination of the aspirates was a valuable adjunctive diagnostic method, whereas immunocytochemistry and DNA-ploidy analysis were not. Immunohistochemical, electron microscopic and cytogenetic analysis were all valuable ancillary methods when performed on surgical specimens. Malignant haemangiopericytoma and fibrosarcoma were the most important differential diagnoses in the FNA specimens.

Induction of metallothionein synthesis in transplanted murine tumors by X irradiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kiyoshi, Shibuya; Masahiko Satoh; Yuzo, Watanabe

1995-07-01

Although recent studies have shown that radiation can induce metallothionein (MT) synthesis in normal tissues, the induction of tumor MT synthesis by irradiation has not been reported. We examined the accumulation of MT in the Meth-A tumor (mouse fibrosarcoma cells) transplanted into mice exposed to whole-body X irradiation. In the present study, the MT content in the tumor cells was increased by X irradiation in a dose-dependent manner. The MT level induced in the tumor cells by X irradiation was elevated not only after a single exposure but also after repeated exposures. Several studies have shown that MT is onemore » of the important cellular factors in resistance to various anti-cancer drugs and ionizing radiation. Thus our results suggest that the radiation-induced MT in the tumor cells may have to be taken into consideration when designing protocols for radio-and chemotherapy. 29 refs., 3 figs.« less

Nasal osteoma in a dairy cow: a combined clinical, imaging and histopathological approach to diagnosis.

PubMed

Wuersch, K; Bischoff, M; Thoma, R; Matter, M S

2009-01-01

An 8-year-old Brown Swiss dairy cow was presented with unilateral epistaxis and mild inspiratory stridor. At that time endoscopic examination revealed a smooth-surfaced mass within the left nasal cavity. Biopsy samples were collected and a diagnosis of fibrosarcoma was made. Eighteen months later the animal developed severe respiratory distress that led to difficulties in feeding and consequently to emaciation and a dramatic drop in milk production. The cow was humanely destroyed and submitted for post-mortem examination. The head was subject to further investigation by radiography, computed tomography and magnetic resonance imaging. These techniques revealed a non-infiltrative, well-circumscribed mass of both radiodense and heterogeneously intense structures. Histopathological examination revealed a mass consisting of well-differentiated and interlacing bone trabeculae lined by osteoblasts and multinucleated osteoclasts. In contrast to the initial diagnosis, the later diagnostic approaches supported the diagnosis of osteoma.

Laser-induced fluorescence in malignant and normal tissue in mice injected with two different carotenoporphyrins.

PubMed Central

Nilsson, H.; Johansson, J.; Svanberg, K.; Svanberg, S.; Jori, G.; Reddi, E.; Segalla, A.; Gust, D.; Moore, A. L.; Moore, T. A.

1994-01-01

Laser-induced fluorescence (LIF) was used to characterise the localisation of an intravenously administered trimethylated carotenoporphyrin [CP(Me)3] and a trimethoxylated carotenoporphyrin [CP(OMe)3] in an intramuscularly transplanted malignant tumour (MS-2 fibrosarcoma) and healthy muscle in female Balb/c mice, 3, 24, 48 and 96 h post injection. The fluorescence was induced with a dye laser pumped by a nitrogen laser, emitting light at 425 nm. The fluorescence spectra were recorded in the region 455-760 nm using a polychromator equipped with an image-intensified CCD camera. The tumour/peritumoral muscle ratio was about 5:1 for CP(Me)3 and about 6:1 for CP(OMe)3 in terms of the background-free fluorescence intensity, which peaked at about 655 nm. By including the endogenous tissue fluorescence, the contrast was further enhanced by a factor of approximately 2. PMID:7947092

Effect of asoka on the intracellular glutathione levels and skin tumour promotion in mice.

PubMed

Varghese, C D; Nair, S C; Panikkar, B; Panikkar, K R

1993-04-15

The bark of Saraka asoca (asoka) is commonly used to treat various diseases by the Indian system of medicine and in Sri Lanka. Further purification and chemical analysis of the active compound from the bark extract of asoka showed that (-)-epicatechin was responsible for the observed antitumour/anticarcinogenic activity. Papilloma formation in mice initiated with 7,12-dimethylbenz[a]anthracene (DMBA) and promoted using croton oil was inhibited by the topical application of 100 mg/kg body weight (b.w.) of (-)-epicatechin isolated from asoka bark extract. Oral administration of the same dose restricted the growth of s.c. injected 20 methylcholanthrene (MCA) induced soil tissue fibrosarcomas significantly in mice. Elevations of almost 2-4-fold in the intracellular reduced glutathione and related enzymes viz., glutathione reductase and glutathione S-transferase of sarcoma-180 tumour cells were noted in the presence of 1 microgram/ml of (-)-epicatechin, further highlighting its antiproliferative effect.

Imaging thiol redox status in murine tumors in vivo with rapid-scan electron paramagnetic resonance

NASA Astrophysics Data System (ADS)

Epel, Boris; Sundramoorthy, Subramanian V.; Krzykawska-Serda, Martyna; Maggio, Matthew C.; Tseytlin, Mark; Eaton, Gareth R.; Eaton, Sandra S.; Rosen, Gerald M.; Kao, Joseph P. Y.; Halpern, Howard J.

2017-03-01

Thiol redox status is an important physiologic parameter that affects the success or failure of cancer treatment. Rapid scan electron paramagnetic resonance (RS EPR) is a novel technique that has shown higher signal-to-noise ratio than conventional continuous-wave EPR in in vitro studies. Here we used RS EPR to acquire rapid three-dimensional images of the thiol redox status of tumors in living mice. This work presents, for the first time, in vivo RS EPR images of the kinetics of the reaction of 2H,15N-substituted disulfide-linked dinitroxide (PxSSPx) spin probe with intracellular glutathione. The cleavage rate is proportional to the intracellular glutathione concentration. Feasibility was demonstrated in a FSa fibrosarcoma tumor model in C3H mice. Similar to other in vivo and cell model studies, decreasing intracellular glutathione concentration by treating mice with L-buthionine sulfoximine (BSO) markedly altered the kinetic images.

Systemic vasculitis associated with vemurafenib treatment: Case report and literature review.

PubMed

Mirouse, Adrien; Savey, Léa; Domont, Fanny; Comarmond, Cloé; Barete, Stéphane; Plaisier, Emmanuelle; Rouvier, Philippe; Cacoub, Patrice; Saadoun, David

2016-11-01

Vemurafenib, an inhibitor of mutated B-rapidly accelerated fibrosarcoma, is frequently used in the treatment of melanoma and Erdheim-Chester disease (ECD) patients. Inflammatory adverse effects have been increasingly reported after vemurafenib treatment. We report 6 cases of vemurafenib-associated vasculitis, of whom a personal case of a 75-year-old man with history of ECD who developed purpura and rapidly progressive pauci-immune glomerulonephritis during treatment with vemurafenib. In the 5 others cases from the literature, all patients presented skin vasculitis, and with joint involvement in 60% of them. Vemurafenib treatment was stopped (n = 3), continued at reduced doses (n = 1), or continued at the same dose (n = 2). Three patients (50%) received corticosteroids combined with cyclophosphamide (n = 1), and all achieved remission of vasculitis. One patient experienced vasculitis relapse after vemurafenib therapy was restarted. Systemic vasculitis is a rare vemurafenib-associated adverse event that may be life-threatening.

Identification and characterization of a human smad3 splicing variant lacking part of the linker region.

PubMed

Kjellman, Christian; Honeth, Gabriella; Järnum, Sofia; Lindvall, Magnus; Darabi, Anna; Nilsson, Ingar; Edvardsen, Klaus; Salford, Leif G; Widegren, Bengt

2004-03-03

Smad3 is one of the signal transducers that are activated in response to transforming growth factor-beta (TGF-beta). We have identified and characterized a splicing variant of smad3. The splicing variant (smad3-Delta3) lacks exon 3 resulting in a truncated linker region. We could detect mRNA expression of smad3-Delta3 in all investigated human tissues. Real-time PCR analyses demonstrated that the fraction of smad3-Delta3 mRNA compared to normal smad3 varies between tissues. The amount of spliced mRNA was estimated to represent 0.5-5% of the normal smad3 mRNA. When smad3-Delta3 is overexpressed in a fibrosarcoma cell line, the Smad3-Delta3 is translocated to the nucleus upon TGF-beta stimulation and binds the Smad responsive element. Using a CAGA luciferase reporter system, we demonstrate that Smad3-Delta3 has transcriptional activity and we conclude that Smad3-Delta3 possesses functional transactivating properties.

Synthesis, Biological Evaluation, and Structure–Activity Relationships of Novel Substituted N-Phenyl Ureidobenzenesulfonate Derivatives Blocking Cell Cycle Progression in S-Phase and Inducing DNA Double-Strand Breaks

PubMed Central

2012-01-01

Twenty-eight new substituted N-phenyl ureidobenzenesulfonate (PUB-SO) and 18 N-phenylureidobenzenesulfonamide (PUB-SA) derivatives were prepared. Several PUB-SOs exhibited antiproliferative activity at the micromolar level against the HT-29, M21, and MCF-7 cell lines and blocked cell cycle progression in S-phase similarly to cisplatin. In addition, PUB-SOs induced histone H2AX (γH2AX) phosphorylation, indicating that these molecules induce DNA double-strand breaks. In contrast, PUB-SAs were less active than PUB-SOs and did not block cell cycle progression in S-phase. Finally, PUB-SOs 4 and 46 exhibited potent antitumor activity in HT-1080 fibrosarcoma cells grafted onto chick chorioallantoic membranes, which was similar to cisplatin and combretastatin A-4 and without significant toxicity toward chick embryos. These new compounds are members of a promising new class of anticancer agents. PMID:22694057

Synthesis, biological evaluation, and structure-activity relationships of novel substituted N-phenyl ureidobenzenesulfonate derivatives blocking cell cycle progression in S-phase and inducing DNA double-strand breaks.

PubMed

Turcotte, Vanessa; Fortin, Sébastien; Vevey, Florence; Coulombe, Yan; Lacroix, Jacques; Côté, Marie-France; Masson, Jean-Yves; C-Gaudreault, René

2012-07-12

Twenty-eight new substituted N-phenyl ureidobenzenesulfonate (PUB-SO) and 18 N-phenylureidobenzenesulfonamide (PUB-SA) derivatives were prepared. Several PUB-SOs exhibited antiproliferative activity at the micromolar level against the HT-29, M21, and MCF-7 cell lines and blocked cell cycle progression in S-phase similarly to cisplatin. In addition, PUB-SOs induced histone H2AX (γH2AX) phosphorylation, indicating that these molecules induce DNA double-strand breaks. In contrast, PUB-SAs were less active than PUB-SOs and did not block cell cycle progression in S-phase. Finally, PUB-SOs 4 and 46 exhibited potent antitumor activity in HT-1080 fibrosarcoma cells grafted onto chick chorioallantoic membranes, which was similar to cisplatin and combretastatin A-4 and without significant toxicity toward chick embryos. These new compounds are members of a promising new class of anticancer agents.

Suppression of tumor cell invasiveness by hydrolyzable tannins (plant polyphenols) via the inhibition of matrix metalloproteinase-2/-9 activity.

PubMed

Tanimura, Susumu; Kadomoto, Ryoji; Tanaka, Takashi; Zhang, Ying-Jun; Kouno, Isao; Kohno, Michiaki

2005-05-20

Elevated expression of matrix metalloproteinases (MMPs), especially that of MMP-2 and MMP-9, is associated with increased metastatic potential in many tumor cells. Recently, green tea polyphenol epigallocatechin-3-O-gallate (EGCG) has been shown to inhibit the MMP-2/-9 activity as well as the invasiveness of tumor cells. In this study, we have examined the inhibitory effect of hydrolyzable tannins (plant polyphenols) on the tumor cell invasion. Our results demonstrate that beta-d-glucose whose hydroxy groups are substituted entirely with galloyl group and further some of them are cross-linked to form hexahydroxydiphenoyl group, for example, suppresses the invasiveness of tumor cells much more potently than EGCG via direct inhibition of the MMP-2/-9 activity. Among those examined, 1,2,4-tri-O-galloyl-3,6-hexahydroxydiphenoyl-beta-d-glucose (punicafolin) inhibits the invasion of HT1080 fibrosarcoma cells most potently. These hydrolyzable tannins would provide new leads for the development of potent inhibitors against tumor metastasis.

Synthesis and surface modification of magnetic nanoparticles for potential applications in sarcomas

NASA Astrophysics Data System (ADS)

Shahbazi, S.; Wang, X.; Yang, J.-L.; Jiang, X. C.; Ryan, R.; Yu, A. B.

2015-06-01

The application of nano-science in cancer therapy has become one of the most attractive tools in scientific research because of its versatility in diagnosis and treatment. Among the different types of nanoparticles, iron oxide nanoparticles (IONPs) are renowned for their low toxicity and suitability for therapeutic and diagnostic, or `theragnostic,' approach against different types of cancers. Research investigating the effect of IONPs with different physiochemical characteristics in sarcoma is limited. In this study, we initially prepared IONPs of different sizes (200, 100, 20, and 10 nm) and modified their surface with different types of coatings (polyethylene glycol, d-glucose, and silica) under mild conditions. Various methods were used to illustrate and quantify cellular uptake of magnetic nanoparticles in sarcoma cell lines. Finally, the safety of the uptaken nanoparticles on diverse human sarcoma cell lines was investigated and found that the readily available IONPs can be taken up by synovial sarcoma and liposarcoma cell lines in the selective histological tumor types; however, they seem highly toxic for fibrous histiocytoma and fibrosarcoma.

Combined radiotherapy and Corynebacterium parvum treatment of rat tumors with different immunogenicity. [X rays

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moroson, H.; Stowe, S.; Rotman, M.

1978-01-01

Evidence is presented that combined radiotherapy and Corynebacterium parvum treatment gives better results than radiotherapy alone in rats bearing a chemically-induced highly-immunogenic transplanted fibrosarcoma termed BP 179; however, similar behavior is not observed with either of two weakly-immunogenic mammary carcinomas, 13762 or ME/H. Relative immunogenicity is determined by the ability of immunized rats to reject tumor cell challenge. Both 13762 and ME/H carcinomata grow progressively and metastasize early to the retroperitoneal cavity and lungs if they are left untreated. Local radiotherapy of the primary tumor has no influence on growth of metastases whether it is combined with C. parvum ormore » not. Results of cell-mediated cytotoxicity studies with lymphocytes from BP 179 and ME/H tumor bearing rats treated with radiation or radiation plus C. parvum support the in vivo findings of combined radiotherapy. These data suggest that unlike strongly immunogenic tumors, weakly immunogenic tumors will not respond better to C. parvum combined with radiation therapy.« less

Influence of ingested ethanol on Photofrin clearance in mice

NASA Astrophysics Data System (ADS)

Montague, Donna; Fink, Louis; Stone, Angie; Flock, Stephen T.

1993-06-01

A series of experiments have been undertaken to ascertain the influence of dietary additives on the clearance of Photofrin. Post-treatment cutaneous photosensitivity continues to be a significant side effect of photodynamic therapy (PDT) in humans. Cutaneous photosensitivity in humans is evidenced by erythema and edema in exposed areas. Murine models were chosen to investigate the differences in cutaneous photosensitivity as measured by footpad thickness in the presence or absence of dietary additives. Additionally, radiation induced fibrosarcoma (RIF) cells were implanted into the subcutaneous space on the dorsal aspect of the foot. In this case, the effect of PDT on tumor growth kinetics was assumed to be proportional to Photofrin concentration. Photofrin concentrations in tumors were measured by HPLC. Serum levels for dietary additives were obtained where analytical methods were available. Ingested ethanol increased the clearance rate of Photofrin as demonstrated by measurements of Photofrin tumor concentration and by failure of RIF tumor to respond to PDT in groups treated with ethanol compared to controls.

Identification of matrix metalloproteinase inhibitors by chemical arrays.

PubMed

Kawatani, Makoto; Fukushima, Yukako; Kondoh, Yasumitsu; Honda, Kaori; Sekine, Tomomi; Yamaguchi, Yoshiki; Taniguchi, Naoyuki; Osada, Hiroyuki

2015-01-01

Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases that degrade many extracellular matrix components and that have been implicated in the pathogenesis of various human diseases including cancer metastasis. Here, we screened MMP-9 inhibitors using photo-cross-linked chemical arrays, which can detect small-molecule ligand-protein interactions on a chip in a high-throughput manner. The array slides were probed sequentially with His-MMP-9, anti-His antibody, and a Cy5-labeled secondary antibody and then scanned with a microarray scanner. We obtained 27 hits among 24,275 compounds from the NPDepo library; 2 of the identified compounds (isoxazole compound 1 and naphthofluorescein) inhibited MMP-9 enzyme activity in vitro. We further explored 17 analogs of 1 and found that compound 18 had the strongest inhibitory activity. Compound 18 also inhibited other MMPs, including MMP-2, MMP-12, and MMP-13 and significantly inhibited cell migration in human fibrosarcoma HT1080 cells. These results suggest that 18 is a broad-spectrum MMP inhibitor.

Formation of solid tumors by a single multinucleated cancer cel

PubMed Central

Weihua, Zhang; Lin, Qingtang; Ramoth, Asa J.; Fan, Dominic; Fidler, Isaiah J.

2011-01-01

BACKGROUND Large multinucleated cells (MNC) commonly exist in tumorigenic cancer cell lines widely used in research, but their contributions to tumorigenesis are unknown. METHODS In this study, we characterized MNCs in the murine fibrosarcoma cell line UV-2237 in vitro and in vivo at a single cell level. RESULTS We observed that MNCs originated from a rare subpopulation of mononuclear cells; MNCs were positive for a senescent marker, β-galacosidase (SA-β-Gal); MNCs were responsible for the majority of clonogenic activity when cultured in hard agar; MNCs were more resistant to chemotherapeutic agents than were mononuclear cells; MNCs could undergo asymmetric division (producing mononuclear cells) and self-renewal in vitro and in vivo; and, most importantly a single MNC produced orthotopic subcutaneous tumors (composed mainly of mononuclear cells) that gave rise to spontaneous lung metastases in nude mice. CONCLUSIONS MNCs can be growth-arrested under stress, are highly resistant to chemotherapy, and can generate clonal orthotopic metastatic tumors PMID:21365635

[Clinical analysis of 48 cases sarcoma in nasal cavity and sinuses].

PubMed

Yang, Chengzhang; Zhang, Dan

2004-10-01

To enhance the level of diagnose and treatment of sarcoma in nasal cavity and sinuses by studying the clinical features, diagnosis and treatment of 48 cases sarcoma in nasal cavity and sinuses. Forty-eight cases sarcoma in nasal cavity and sinuses treated from 1995 to 2000 were analyzed retrospectively. Fibrosarcoma in 4 cases, malignant fibrous histiocytoma in 3 cases, liposarcoma in 4 cases, leiomyosarcoma in 5 cases, rhabdomyosarcoma in 5 cases, osteosarcoma in 2 cases, chondrosarcoma in 3 cases, malignant melanoma in 4 cases, non-Hogkin's in 4 cases, extramedullary plasmacytoma in 1 case, Schwannoma in 5 cases, esthesioneuroblastoma in 5 cases, angiosarcoma in 3 cases. Following-up after synthetic treatment, the 1, 3, 5 year survival rates were 62.5%, 46.7%, 35.7% respectively. Sarcoma in nasal cavity and sinuses is not easy to diagnose definitely, immunohistochemistry is helpful for pathological diagnose. It's easy to recurrent and metastasis and it's beneficial to improve prognosis with synthetic treatment.

Radiotherapy of soft tissue sarcomas in dogs.

PubMed

McChesney, S L; Withrow, S J; Gillette, E L; Powers, B E; Dewhirst, M W

1989-01-01

Megavoltage radiotherapy was administered to 42 dogs with soft tissue sarcoma. Acceptable local control of these aggressive tumors was achieved after one year of treatment. Control rates of 48 and 67% were obtained at doses of 45 and 50 gray (Gy), respectively. At 2 years, control rates decreased to 33% at the dose of 50 Gy. Serious complications developed in 4 of 42 dogs at doses of 40 to 50 Gy. The estimated dose with a 50% probability for causing serious complications was 54 Gy, given in 10 fractions. We believe that the large doses per fraction used in this study probably led to an increased probability for necrosis. Hemangiopericytomas seemed to be more responsive than fibrosarcomas. Only 2 of 11 recurrent tumors were controlled with surgery. Good local control was achieved with radiation alone for one year at doses with a low probability for serious complications; however, higher total radiation doses or combined modalities, such as surgery and radiation or radiation and hyperthermia, may be needed for longer-term control.

Neoplastic and Nonneoplastic Cutaneous Tumors of Dogs in Grenada, West Indies

PubMed Central

Chikweto, A.; McNeil, P.; Bhaiyat, M. I.; Stone, D.; Sharma, R. N.

2011-01-01

This retrospective survey was undertaken between 2002 and 2007 on samples from dogs residing in Grenada. The objectives of the study were to identify the most common histologic types of canine cutaneous tumors, determine the relative frequency of each tumor type, and compare results to reports from other regions. In a series of 225 skin masses examined, the proportion of neoplasms was 72% whereas nonneoplastic tumors accounted for 15.6%, and inflammatory conditions constituted 12.4%. There were 10 types of nonneoplastic tumors with hamartomas being the most common (28.5%), followed by sebaceous hyperplasia (25.7%) and fibroepithelial polyps (22.8%). The 10 most common cutaneous neoplasms were hemangiosarcomas (19.1%), histiocytomas (8.6%), melanocytomas (8%), mast cell tumors (6.8%), lipomas (6.8%), hemangiopericytomas (6.2%), papillomas (5.6%), fibrosarcomas (5.6%), hemangiomas (4.9%), and squamous cell carcinomas (4.3%). Tumors of vascular origin and transmissible venereal tumors were more common in dogs in our study than reported from other regions. PMID:23738097

Gelatin promotes murine fibrosarcoma L929 cell detachment and protects the cells from TNFα-induced cytotoxicity.

PubMed

Wang, Hong-Ju; Li, Meng-Qi; Liu, Wei; Yao, Guo-Dong; Xia, Ming-Yu; Hayashi, Toshihiko; Fujisaki, Hitomi; Hattori, Shunji; Tashiro, Shin-Ichi; Onodera, Satoshi; Ikejima, Takashi

2016-07-01

Gelatin has been considered to exist as intermediate substance of collagen catabolism in tissue remodeling or under inflammatory conditions. We have initiated the study on possible biological functions of gelatin that can exist temporally and locally under the conditions of remodeling and inflammation Materials and methods: To this purpose, we investigated cell proliferation and survival on gelatin-coated dishes and the response to tumor necrosis factor α (TNFα)-induced cytotoxicity in L929 cells. Autophagy level, ATP level, and ROS generation are examined. L929 cells detached from the gelatin-coated dishes and formed multicellular aggregates. TNFα-induced cytotoxicity in L929 cells was inhibited by gelatin-coating culture. The cells on gelatin-coated dishes showed reduced cellular ATP levels and increased adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) phosphorylation, leading to increased ROS generation and autophagy. This study showed that gelatin-coated culture protected L929 cells from TNFα-induced cytotoxicity and suggested for a possible pathophysiological function of gelatin in regulating cellular functions.

Primary Fibro Sarcoma of the Heart

PubMed Central

Kabashi, Serbeze; Hoxha, Naim; Gashi, Shkelzen; Ahmegjekaj, Ilir; Bejta, Ilir; Sadiku, Muharrem; Ymeri, Halit; Kabashi, Antigona; Bicaj, Xhavit; Mucaj, Sefedin

2013-01-01

Primary malignant heart tumors represent rare entities where fibro sarcoma represents about 3% of all. Introducing the patient: A 15 years old patient with cardiac insufficiency (heart failure) symptoms, such as weakness, cyanosis, palpitations and breathing difficulties; enlargement of upper mediastinum and pleural effusion. Through echocardiography a pericardial effusion and intracavitary thrombus in atrium was diagnosed. With computed tomography is diagnosed a tumoral mass in right atrium which is also spread in the right ventricle of the heart. Tumor is completely removed; pat histology result showed primary fibro sarcoma of the heart. At that time no metastasis was found. Conclusion. Primary malignant heart tumors may manifest like cardiac insufficiency or like systemic diseases. Fibrosarcomas are rare and have bad prognosis. On average patients can live around six months after initial symptoms appeared and diagnosis of the tumor was done. In the case of cardiac insufficiency with differential diagnosis we should also think of heart tumors, which could certainly be proved for or eliminated by echocardiography. PMID:24167396

Primary fibro sarcoma of the heart.

PubMed

Kabashi, Serbeze; Hoxha, Naim; Gashi, Shkelzen; Ahmegjekaj, Ilir; Bejta, Ilir; Sadiku, Muharrem; Ymeri, Halit; Kabashi, Antigona; Bicaj, Xhavit; Mucaj, Sefedin

2013-01-01

Primary malignant heart tumors represent rare entities where fibro sarcoma represents about 3% of all. Introducing the patient: A 15 years old patient with cardiac insufficiency (heart failure) symptoms, such as weakness, cyanosis, palpitations and breathing difficulties; enlargement of upper mediastinum and pleural effusion. Through echocardiography a pericardial effusion and intracavitary thrombus in atrium was diagnosed. With computed tomography is diagnosed a tumoral mass in right atrium which is also spread in the right ventricle of the heart. Tumor is completely removed; pat histology result showed primary fibro sarcoma of the heart. At that time no metastasis was found. Conclusion. Primary malignant heart tumors may manifest like cardiac insufficiency or like systemic diseases. Fibrosarcomas are rare and have bad prognosis. On average patients can live around six months after initial symptoms appeared and diagnosis of the tumor was done. In the case of cardiac insufficiency with differential diagnosis we should also think of heart tumors, which could certainly be proved for or eliminated by echocardiography.

17 O MRS assesses the effect of mild hypothermia on oxygen consumption rate in tumors.

PubMed

Neveu, Marie-Aline; Joudiou, Nicolas; De Preter, Géraldine; Dehoux, Jean-Paul; Jordan, Bénédicte F; Gallez, Bernard

2017-08-01

Although oxygen consumption is a key factor in metabolic phenotyping, its assessment in tumors remains critical, as current technologies generally display poor specificity. The objectives of this study were to explore the feasibility of direct 17 O nuclear magnetic resonance (NMR) spectroscopy to assess oxygen metabolism in tumors and its modulations. To investigate the impact of hypometabolism induction in the murine fibrosarcoma FSAII tumor model, we monitored the oxygen consumption of normothermic (37°C) and hypothermic (32°C) tumor-bearing mice. Hypothermic animals showed an increase in tumor pO 2 (measured by electron paramagnetic resonance oximetry) contrary to normothermic animals. This was related to a decrease in oxygen consumption rate (assessed using 17 O magnetic resonance spectroscopy (MRS) after the inhalation of 17 O 2 -enriched gas). This study highlights the ability of direct 17 O MRS to measure oxygen metabolism in tumors and modulations of tumor oxygen consumption rate. Copyright © 2017 John Wiley & Sons, Ltd.

Experimental tumor growth of canine osteosarcoma cell line on chick embryo chorioallantoic membrane (in vivo studies).

PubMed

Walewska, Magdalena; Dolka, Izabella; Małek, Anna; Wojtalewicz, Anna; Wojtkowska, Agata; Żbikowski, Artur; Lechowski, Roman; Zabielska-Koczywąs, Katarzyna

2017-05-12

The chick embryo chorioallantoic membrane (CAM) model is extensively used in human medicine in preclinical oncological studies. The CAM model has several advantages: low cost, simple experimental approach, time saving and following "3R principles". Research has shown that the human osteosarcoma cell lines U2OS, MMNG-HOS, and SAOS can form tumors on the CAM. In veterinary medicine, this has been described only for feline fibrosarcomas, feline mammary carcinomas and canine osteosarcomas. However, in case of canine osteosarcomas, it has been shown that only non-adherent osteosarcoma stem cells isolated from KTOSA5 and CSKOS cell lines have the ability to form microtumors on the CAM after an incubation period of 5 days, in contrast to adherent KTOSA5 and CSKOS cells. In the presented study, we have proven that the commercial adherent canine osteosarcoma cell line (D-17) can form vascularized tumors on the CAM after the incubation period of 10 days.

A programmable synthetic lineage-control network that differentiates human IPSCs into glucose-sensitive insulin-secreting beta-like cells

PubMed Central

Saxena, Pratik; Heng, Boon Chin; Bai, Peng; Folcher, Marc; Zulewski, Henryk; Fussenegger, Martin

2016-01-01

Synthetic biology has advanced the design of standardized transcription control devices that programme cellular behaviour. By coupling synthetic signalling cascade- and transcription factor-based gene switches with reverse and differential sensitivity to the licensed food additive vanillic acid, we designed a synthetic lineage-control network combining vanillic acid-triggered mutually exclusive expression switches for the transcription factors Ngn3 (neurogenin 3; OFF-ON-OFF) and Pdx1 (pancreatic and duodenal homeobox 1; ON-OFF-ON) with the concomitant induction of MafA (V-maf musculoaponeurotic fibrosarcoma oncogene homologue A; OFF-ON). This designer network consisting of different network topologies orchestrating the timely control of transgenic and genomic Ngn3, Pdx1 and MafA variants is able to programme human induced pluripotent stem cells (hIPSCs)-derived pancreatic progenitor cells into glucose-sensitive insulin-secreting beta-like cells, whose glucose-stimulated insulin-release dynamics are comparable to human pancreatic islets. Synthetic lineage-control networks may provide the missing link to genetically programme somatic cells into autologous cell phenotypes for regenerative medicine. PMID:27063289

Comparative dermal carcinogenesis of shale and petroleum-derived distillates.

PubMed

Clark, C R; Walter, M K; Ferguson, P W; Katchen, M

1988-03-01

Ten test materials derived from petroleum or hydrotreated shale oils were applied 3 times/week for up to 105 weeks to the shaved skin of 25 male and 25 female C3H/HeN mice per group. Mineral oil and benzo(a) pyrene (0.15%) were control materials. Clinical observations were recorded during the study. At death, histopathologic examination was conducted on skin, internal organs and any gross lesions. Exposures to some materials were ended midway in the study due to severe irritation. Chronic toxicity of all materials was limited to inflammatory and degenerative skin changes. Significant increases over control incidence of skin tumors (squamous cell carcinoma and fibrosarcoma) occurred with both petroleum and shale-derived naphtha (21%, 50%), Jet A (26%, 28%), JP-4 (26%, 50%), and crude oils (84%, 54%). Severely hydrotreated shale oil and petroleum and shale-derived diesel distillates were not considered tumorigenic. Results indicate that toxicity of comparable petroleum and shale-derived fractions was qualitatively similar and confirm earlier findings that hydrotreating reduces or eliminates carcinogenicity of raw shale oil.

NGR-modified pH-sensitive liposomes for controlled release and tumor target delivery of docetaxel.

PubMed

Gu, Zili; Chang, Minglu; Fan, Yang; Shi, Yanbin; Lin, Guimei

2017-12-01

As current tumor chemotherapy faces many challenges, it is important to develop drug delivery systems with increased tumor-targeting ability, enhanced therapeutic effects and reduced side effects. In this study, a pH-sensitive liposome was constructed containing CHEMS-anchored PEG2000 for extended circulation and NGR peptide as the targeting moiety. The NGR-modified docetaxel-loaded pH-sensitive extended-circulation liposomes (DTX/NGR-PLL) prepared possess suitable physiochemical properties, including particle size of approximately 200nm, drug encapsulation efficiency of approximately 70%, and pH-sensitive drug release properties. Experiments performed in vitro and in vivo on human fibrosarcoma cells (HT-1080) and human breast adenocarcinoma cells (MCF-7) verified the specific targeting ability and enhanced antitumor activity to HT-1080 cells. The results of intravenous administration demonstrated that NGR-modified liposomes can significantly and safely accumulate in tumor tissue in xenografted nude mice. In conclusion, the liposomes constructed hold promise as a safe and efficient drug delivery system for specific tumor treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

Use of Oil Red O stain in the cytologic diagnosis of canine liposarcoma.

PubMed

Masserdotti, Carlo; Bonfanti, Ugo; De Lorenzi, Davide; Ottolini, Nicola

2006-03-01

Oil Red O, a stain commonly used to demonstrate lipid in frozen tissue, also may be used to stain air-dried cytologic specimens. The purpose of this study was to prospectively evaluate the value of Oil Red O in identifying lipid to aid in the differentiation of liposarcomas from other types of sarcoma. Twelve tumor specimens from dogs were evaluated. The tumors were included in the study if initial cytologic evaluation indicated a sarcoma, and if histologic confirmation was available. Oil Red O was applied to all cytologic specimens. Tumor specimens were diagnosed histologically as liposarcoma (3 well-differentiated, 1 pleomorphic), hemangiopericytoma (n = 3), fibrosarcoma (n = 3), malignant fibrous histiocytoma (n = 1), and undifferentiated sarcoma (n = 1). Cytologic specimens from all liposarcomas showed strong positive staining of cytoplasmic vacuoles for lipid. Specimens from other sarcomas stained negative for Oil Red O, with the exception of weak, irregular positive staining in 1 hemangiopericytoma. Our results suggest that Oil Red O staining may be an easy, inexpensive, and useful diagnostic tool for the differentiation of liposarcoma from other mesenchymal neoplasms.

Cytotoxic constituents of propolis from Myanmar and their structure-activity relationship.

PubMed

Li, Feng; Awale, Suresh; Tezuka, Yasuhiro; Kadota, Shigetoshi

2009-12-01

Thirteen cycloartane-type tritepenes (1-13) and four prenylated flavanones (14-17) isolated from propolis collected in Myanmar, were evaluated for their cytotoxic activity against a panel of six different cancer cell lines; three murine cancer cell lines (colon 26-L5 carcinoma, B16-BL6 melanoma, and Lewis lung carcinoma) and three human cancer cell lines (lung A549 adenocarcinoma, cervix HeLa adenocarcinoma and HT-1080 fibrosarcoma). Among them, a cycloartane-type triterpene, 3alpha,27-dihydroxycycloart-24E-en-26-oic acid (3), showed the most potent cytotoxicity against B16-BL6 cells with an IC(50) value of 5.91 microM, comparable to those of positive controls, doxorubicin (IC(50), 5.66 microM) and 5-fluorouracil (IC(50), 4.88 microM). In addition, (2S)-5,7-dihydroxy-4'-methoxy-8,3'-diprenylflavanone (14) exhibited strong cytotoxicity against all the tested cancer cell lines with the IC(50) values ranging from 14.0 to 26.4 microM. Based on the observed results, the structure-activity relationships are discussed.

Cytotoxic constituents of Soymida febrifuga from Myanmar.

PubMed

Awale, Suresh; Miyamoto, Tatsuya; Linn, Thein Zaw; Li, Feng; Win, Nwet Nwet; Tezuka, Yasuhiro; Esumi, Hiroyasu; Kadota, Shigetoshi

2009-09-01

The 70% ethanol extract of Soymida febrifuga was found to kill PANC-1 human pancreatic cancer cells preferentially under nutrition-deprived conditions at a concentration of 10 microg/mL. Phytochemical investigation led to the isolation of 27 compounds including four new compounds [(3R)-6,4'-dihydroxy-8-methoxyhomoisoflavan (1), (2R)-7,4'-dihydroxy-5-methoxy-8-methylflavan (2), 7-hydroxy-6-methoxy-3-(4'-hydroxybenzyl)coumarin (3), and 6-hydroxy-7-methoxy-3-(4'-hydroxybenzyl)coumarin (4)]. 2',4'-Dihydroxychalcone (8) displayed the most potent preferential cytotoxicity (PC(50) 19.0 microM) against PANC-1 cells. In addition, the cytotoxic activity against colon 26-L5 carcinoma (colon 26-L5), B16-BL6 melanoma (B16-BL6), lung A549 adenocarcinoma (A549), cervix HeLa adenocarcinoma (HeLa), and HT-1080 fibrosarcoma (HT-1080) cell lines and their structure-activity relationship are discussed. The cytotoxic activity of 4'-hydroxy-3,5-dimethoxystilbene (6) against colon 26-L5 (IC(50) 2.96 microM) was found to be stronger than the positive control, doxorubicin, at IC(50) 3.12 microM.

Activating the nuclear piston mechanism of 3D migration in tumor cells

PubMed Central

2017-01-01

Primary human fibroblasts have the remarkable ability to use their nucleus like a piston, switching from low- to high-pressure protrusions in response to the surrounding three-dimensional (3D) matrix. Although migrating tumor cells can also change how they migrate in response to the 3D matrix, it is not clear if they can switch between high- and low-pressure protrusions like primary fibroblasts. We report that unlike primary fibroblasts, the nuclear piston is not active in fibrosarcoma cells. Protease inhibition rescued the nuclear piston mechanism in polarized HT1080 and SW684 cells and generated compartmentalized pressure. Achieving compartmentalized pressure required the nucleoskeleton–cytoskeleton linker protein nesprin 3, actomyosin contractility, and integrin-mediated adhesion, consistent with lobopodia-based fibroblast migration. In addition, this activation of the nuclear piston mechanism slowed the 3D movement of HT1080 cells. Together, these data indicate that inhibiting protease activity during polarized tumor cell 3D migration is sufficient to restore the nuclear piston migration mechanism with compartmentalized pressure characteristic of nonmalignant cells. PMID:27998990

Radioprotection of mouse skin vasculature and the RIF-1 fibrosarcoma by WR-2721

DOE Office of Scientific and Technical Information (OSTI.GOV)

Penhaligon, M.

1984-09-01

The degree of radioprotection obtained with WR-2721 is critically dependent upon the oxygen tension of the tissue concerned. It was therefore considered of interest to examine the response of vascular tissue, which would be supposedly well oxygenated, to treatment with WR-2721 plus X rays. The response of this tissue is of interest because of its role in late radiation damage. In addition, for therapeutic gain an agent must protect normal tissue without concomitant tumor protection. However, data on tumor radioprotection have been conflicting and therefore the effect of WR-2721 on an experimental tumor was also tested. Vascular damage was assessedmore » using the fact that tumors grow more slowly in irradiated beds (Tumor Bed Effect). WR-2721 injected 30 minutes before 5 to 30 Gy X rays protected skin stroma by a factor of 1.6. However, WR-2721 given 10 to 60 minutes before 20 Gy X rays to the RIF-1 tumor had either no effect or was protective, according to the method of immobilizing the mice during irradiation.« less

Reactive oxygen species explicit dosimetry (ROSED) of a type 1 photosensitizer

NASA Astrophysics Data System (ADS)

Ong, Yi Hong; Kim, Michele M.; Huang, Zheng; Zhu, Timothy C.

2018-02-01

Type I photodynamic therapy (PDT) is based on the use of photochemical reactions mediated through an interaction between a tumor-selective photosensitizer, photoexcitation with a specific wavelength of light, and production of reactive oxygen species (ROS). The goal of this study is to develop a model to calculate reactive oxygen species concentration ([ROS]rx) after Tookad®-mediated vascular PDT. Mice with radiation-induced fibrosarcoma (RIF) tumors were treated with different light fluence and fluence rate conditions. Explicit measurements of photosensitizer drug concentration were made via diffuse reflective absorption spectrum using a contact probe before and after PDT. Blood flow and tissue oxygen concentration over time were measured during PDT as a mean to validate the photochemical parameters for the ROSED calculation. Cure index was computed from the rate of tumor regrowth after treatment and was compared against three calculated dose metrics: total light fluence, PDT dose, reacted [ROS]rx. The tumor growth study demonstrates that [ROS]rx serves as a better dosimetric quantity for predicting treatment outcome, as a clinically relevant tumor growth endpoint.

Neoplasia of captive yellow sea horses (Hippocampus kuda) and weedy sea dragons (Phyllopteryx taeniolatus).

PubMed

LePage, Véronique; Dutton, Christopher J; Kummrow, Maya; McLelland, David J; Young, Karrie; Lumsden, John S

2012-03-01

Syngnathidae is the family of fish that includes sea horses, pipefish, and sea dragons. To date, only a single publication has described neoplasia in syngnathids, a fibrosarcoma of the brood pouch in an aquarium-reared lined sea horse (Hippocampus erectus). From 1998 until 2010, the Toronto Zoo submitted 172 syngnathids for postmortem; species included the spotted or yellow sea horse (Hippocampus kuda), the pot-bellied sea horse (Hippocampus abdominalis) and the weedy sea dragon (Phyllopteryx taeniolatus). Seven neoplasms and two neoplastic-like lesions were identified from these cases. Under light microscopy, the neoplasms had morphological characteristics of a cardiac rhabdomyosarcoma, renal adenocarcinoma, renal adenoma, renal round cell tumors, which were likely lymphomas, exocrine pancreatic carcinoma, and intestinal carcinoma. Of these neoplasms, four had clear evidence of metastasis: the pancreatic and intestinal carcinomas and both round cell tumors. As syngnathids are highly fastidious animals, they can be difficult to maintain in captivity. In order to improve their husbandry, preventative and palliative care, as well as treatment, it is important to investigate and document the types of diseases affecting syngnathids.

Subcutaneous fluid port-associated soft tissue sarcoma in a cat.

PubMed

McLeland, Shannon M; Imhoff, Darren J; Thomas, Michelle; Powers, Barb E; Quimby, Jessica M

2013-10-01

A 20-year-old male castrated domestic longhair cat was evaluated for assessment of its chronic kidney disease (CKD) and a non-healing ulcerated mass at the site of a previously placed and subsequently removed GIF tube. The cat had been diagnosed with CKD 10 years prior and two GIF tubes had been placed over a 5-year period, the second of which was associated with secondary infection. Biopsy of the non-healing ulcerated mass was consistent with grade 2 soft tissue sarcoma. At necropsy there was a discrete, serpentine, subcutaneous mass measuring approximately 8 mm in diameter that extended approximately 20 cm along the dorsum to the caudal thorax, following the path of the GIF tube, from the main intrascapular, ulcerated mass where the fluid port injection site was located. This is the first report of a fibrosarcoma arising at the site of a subcutaneous fluid port in a cat. Although the cat's owners were pleased with the 4 years of quality of life provided by this device, this complication should be considered when a decision to place ports for long-term management of disease is made.

Evaluation of formalin-fixed paraffin-embedded tissues obtained from vaccine site-associated sarcomas of cats for DNA of feline immunodeficiency virus.

PubMed

Kidney, B A; Ellis, J A; Haines, D M; Jackson, M L

2000-09-01

To evaluate the use of a polymerase chain reaction (PCR) method for detection of feline immunodeficiency virus (FIV) DNA, using formalin-fixed paraffin-embedded (FFPE) tissues, and to use this method to evaluate tissues obtained from vaccine site-associated sarcomas (VSS) of cats for FIV DNA. 50 FFPE tissue blocks from VSS of cats and 50 FFPE tissue blocks from cutaneous non-vaccine site-associated fibrosarcomas (non-VSS) of cats. DNA was extracted from FFPE sections of each tumor and regions of the gag gene of FIV were amplified by a PCR, using 3 sets of primers. Sensitivity of the method was compared between frozen and FFPE tissues, using splenic tissue obtained from a cat that had been experimentally infected with FIV. We did not detect FIV DNA in VSS or non-VSS tissues. Sensitivity of the PCR method was identical for frozen or FFPE tissues. It is possible to detect FIV DNA in FFPE tissues by use of a PCR. We did not find evidence to support direct FIV involvement in the pathogenesis of VSS in cats.

Diagnosis, treatment and outcome of orbital neoplasia in dogs: a retrospective study of 44 cases.

PubMed

Hendrix, D V; Gelatt, K N

2000-03-01

Forty-four dogs with confirmed orbital neoplasia were studied. Eighteen tumour types were represented and 95 per cent of the neoplasms were classified as malignant. The tumour types most commonly diagnosed were osteosarcoma, fibrosarcoma and nasal adenocarcinoma. Thirty-six per cent of the dogs had at least one clinical sign that was compatible with a diagnosis of orbital abscessation or cellulitis. Fifty-six per cent of the dogs, where follow-up information was available, were euthanased or had died within six months of diagnosis, while 19 per cent of the total were still alive after one year post-diagnosis. Cytological examination was diagnostic for orbital neoplasia in 49 per cent of the fine needle aspirates of the retrobulbar space. In contrast, 56 per cent of the non-surgical biopsies were diagnostic for orbital neoplasia. Of those dogs that had died or been euthanased within six months of diagnosis, only 22 per cent had undergone some form of therapy for orbital neoplasia. In comparison, 86 per cent of dogs surviving longer than six months post-diagnosis had undergone such therapy.

Equine nasal and paranasal sinus tumours. Part 1: review of the literature and tumour classification.

PubMed

Head, K W; Dixon, P M

1999-05-01

The normal gross and histological anatomy of the equine nasal and paranasal sinuses are reviewed and the relationships between the local anatomy, the occurrence of different tumour types, and of tumour spread are examined. The histological classification of the more common equine sinonasal tumours and tumour-like lesions are discussed. Clinical and pathological descriptions of 50 more recently recorded such tumours are separately tabulated. The literature shows that equine sinonasal tumours, both endemic and sporadic, are relatively uncommon in horses, with non-neoplastic growths such as maxillary (sinus) cysts, progressive ethmoid haematoma and inflammatory nasal polyps more commonly recorded. The equine paranasal sinuses, especially the caudal maxillary sinus, are the most common sites for sinonasal tumours and, in contrast to other species, primary nasal tumours are uncommon. The more common tumour types include squamous cell carcinoma that, in some cases, arise in the oral cavity and spread to the maxillary sinuses; adenocarcinomas; bone and dental tumours; fibrosarcomas and haemangiosarcomas. Except for some benign bone tumours, there are few records of successful treatment of equine sinonasal tumours.

Arsenic enhances the apoptosis induced by interferon gamma: key role of IRF-1.

PubMed

El Bougrini, J; Pampin, M; Chelbi-Alix, M K

2006-05-15

Interferons (IFNs) and arsenic trioxide (As2O3) are known inhibitors of cell proliferation and have been used in the treatment of certain forms of malignancy. IFNgamma treatment of cells leads to tyrosine phosphorylation of STAT1 followed by dimerization that accumulates in the nucleus. This is followed by DNA binding, activation of target gene transcription, dephosphorylation, and return to the cytoplasm. We have shown earlier that IFNgamma and As2O3 act synergistically in acute promyelocytic leukemia cells to upregulate IRF-1 expression and to induce apoptosis. Here, we show that in the human fibrosarcoma cell line 2fTGH, As2O3 prolongs IFNgamma-induced STAT1 phosphorylation resulting in persistent binding of STAT1 to GAS motif leading to an increase in IRF-1 expression which correlated with both higher anti-proliferative effect and increased apoptosis. These biological responses induced by IFNgamma alone or in combination with As2O3 were abolished when IRF-1 expression was down-regulated by RNA interference, thus demonstrating the key role of IRF-1.

Enhancing apoptosis in TRAIL-resistant cancer cells using fundamental response rules

PubMed Central

Piras, Vincent; Hayashi, Kentaro; Tomita, Masaru; Selvarajoo, Kumar

2011-01-01

The tumor necrosis factor related apoptosis-inducing ligand (TRAIL) induces apoptosis in malignant cells, while leaving other cells mostly unharmed. However, several carcinomas remain resistant to TRAIL. To investigate the resistance mechanisms in TRAIL-stimulated human fibrosarcoma (HT1080) cells, we developed a computational model to analyze the temporal activation profiles of cell survival (IκB, JNK, p38) and apoptotic (caspase-8 and -3) molecules in wildtype and several (FADD, RIP1, TRAF2 and caspase-8) knock-down conditions. Based on perturbation-response approach utilizing the law of information (signaling flux) conservation, we derived response rules for population-level average cell response. From this approach, i) a FADD-independent pathway to activate p38 and JNK, ii) a crosstalk between RIP1 and p38, and iii) a crosstalk between p62 and JNK are predicted. Notably, subsequent simulations suggest that targeting a novel molecule at p62/sequestosome-1 junction will optimize apoptosis through signaling flux redistribution. This study offers a valuable prospective to sensitive TRAIL-based therapy. PMID:22355661

Critical role of dendritic cell-derived IL-27 in antitumor immunity through regulating the recruitment and activation of NK and NKT cells.

PubMed

Wei, Jun; Xia, Siyuan; Sun, Huayan; Zhang, Song; Wang, Jingya; Zhao, Huiyuan; Wu, Xiaoli; Chen, Xi; Hao, Jianlei; Zhou, Xinglong; Zhu, Zhengmao; Gao, Xiang; Gao, Jian-xin; Wang, Puyue; Wu, Zhenzhou; Zhao, Liqing; Yin, Zhinan

2013-07-01

Critical roles of IL-27 in autoimmune diseases and infections have been reported; however, the contribution of endogenous IL-27 to tumor progression remains elusive. In this study, by using IL-27p28 conditional knockout mice, we demonstrate that IL-27 is critical in protective immune response against methyl-cholanthrene-induced fibrosarcoma and transplanted B16 melanoma, and dendritic cells (DCs) are the primary source. DC-derived IL-27 is required for shaping tumor microenvironment by inducing CXCL-10 expression in myeloid-derived suppressor cells and regulating IL-12 production from DCs, which lead to the recruitment and activation of NK and NKT cells resulting in immunological control of tumors. Indeed, reconstitution of IL-27 or CXCL-10 in tumor site significantly inhibits tumor growth and restores the number and activation of NK and NKT cells. In summary, our study identifies a previous unknown critical role of DC-derived IL-27 in NK and NKT cell-dependent antitumor immunity through shaping tumor microenvironment, and sheds light on developing novel therapeutic approaches based on IL-27.

Long-term effects of intragastic instillations of BDNPF:BDNPA in male Sprague-Dawley rats and female Swiss-Webster mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smith, D.M.; Drake, G.A.; London, J.E.

1981-07-01

Young male Sprague-Dawley rats were given a single dose of 1.3 g/kg body weight (BW) bis-dinitro-propyl-formal:bisdinitro-propyl-acetal (BDNPF:BDNPA) intragastrically (IG) and young female Swiss-Webster mice were given BDNPF:BDNPA either as a single dose (800 mg/kg/Bw) IG or a dose (500 mg/kg/BW) IG on each of 5 consecutive days. All animals were then maintained for the durations of their life spans and autopsied at death. The incidence of testicular Leydig cell tumors and subcutaneous fibrosarcomas in rats receiving the material was significantly elevated compared to controls, though treated animals' life spans were not significantly different from those of control animals. No significantmore » effects were seen in any of the mice receiving either a single dose or multiple doses of BDNPF:BDNPA compared to control animals. We suggest that another species of male Laboratory animals be treated with BDNPF:BDNPA to see if these findings can be replicated.« less

Single-molecule force measurement via optical tweezers reveals different kinetic features of two BRaf mutants responsible for cardio-facial-cutaneous (CFC) syndrome

PubMed Central

Wen, Cheng; Ye, Anpei

2013-01-01

BRaf (B- Rapid Accelerated Fibrosarcoma) protein is an important serine/threonine-protein kinase. Two domains on BRaf can independently bind its upstream kinase, Ras (Rat Sarcoma) protein. These are the Ras binding domain (RBD) and cysteine-rich-domain (CRD). Herein we use customized optical tweezers to compare the Ras binding process in two pathological mutants of BRaf responsible for CFC syndrome, abbreviated BRaf (A246P) and BRaf (Q257R). The two mutants differ in their kinetics of Ras-binding, though both bind Ras with similar increased overall affinity. BRaf (A246P) exhibits a slightly higher Ras/CRD unbinding force and a significantly higher Ras/RBD unbinding force versus the wild type. The contrary phenomenon is observed in the Q257R mutation. Simulations of the unstressed-off rate, koff(0), yield results in accordance with the changes revealed by the mean unbinding force. Our approach can be applied to rapidly assess other mutated proteins to deduce the effects of mutation on their kinetics compared to wild type proteins and to each other. PMID:24409384

A Neolithic case of fibrous dysplasia from Çatalhöyük (Turkey).

PubMed

Milella, Marco; Knüsel, Christopher J; Haddow, Scott D

2016-12-01

The vast majority of primary burials at Neolithic Çatalhöyük (Central Anatolia, Turkey, 7100-6000cal BC) are recovered from beneath house floors, with burials in external spaces extremely rare. Excavations at Çatalhöyük in 1998 brought to light a young adult male buried in a midden (a burial location observed so far for only 4 out of 440 individuals), showing a suite of pathological features affecting the entire skeleton. The observed pathological changes include perimortem and antemortem fractures, proliferative and resorptive areas, thinning of the bone cortex, and localized areas of disorganized spongy bone invaded by fibrous tissue. We propose a differential diagnosis by considering a set of conditions: Paget's disease, osteomyelitis, hyperparathyrhoidism, Ollier's disease, fibrosarcoma, and fibrous dysplasia. The severity and distribution of the observed skeletal changes are consistent with a diagnosis of polyostotic fibrous dysplasia, a possibly debilitating and disfiguring condition. This, together with an unusual depositional context, may suggest a socially-mediated reaction to this individual's infirmity. Copyright © 2016 Elsevier Inc. All rights reserved.

Palladium(II) complexes with N-heteroaromatic bidentate hydrazone ligands: the effect of the chelate ring size and lipophilicity on in vitro cytotoxic activity.

PubMed

Filipović, Nenad; Grubišić, Sonja; Jovanović, Maja; Dulović, Marija; Marković, Ivanka; Klisurić, Olivera; Marinković, Aleksandar; Mitić, Dragana; Anđelković, Katarina; Todorović, Tamara

2014-09-01

Novel Pd(II) complex with N-heteroaromatic Schiff base ligand, derived from 8-quinolinecarboxaldehyde (q8a) and ethyl hydrazinoacetate (haOEt), was synthesized and characterized by analytical and spectroscopy methods. The structure of novel complex, as well as structures of its quinoline and pyridine analogues, was optimized by density functional theory calculations, and theoretical data show good agreement with experimental results. A cytotoxic action of the complexes was evaluated on cultures of human promyelocytic leukemia (HL-60), human glioma (U251), rat glioma (C6), and mouse fibrosarcoma (L929) cell lines. Among investigated compounds, only complexes with quinoline-based ligands reduce the cell numbers in a dose-dependent manner in investigated cell lines. The observed cytotoxic effect of two isomeric quinoline-based complexes is predominantly mediated through the induction of apoptotic cell death in HL-60 cell line. The cytotoxicity of most efficient novel Pd(II) complex is comparable to the activity of cisplatin, in all cell lines investigated. © 2014 John Wiley & Sons A/S.

Cell-based capacitance sensor for analysis of EGFR expression on cell membrane

NASA Astrophysics Data System (ADS)

Shin, Dong-Myeong; Shin, Yong-Cheol; Ha, Ji Hye; Lee, Jong-Ho; Han, Dong-Wook; Kim, Jong-Man; Kim, Hyung Kook; Hwang, Yoon-Hwae

2013-02-01

Cancer cells have many kinds of cancer biomarkers. Among them, the epidermal growth factor (EGF) receptors can show a possibility for a cancer marker because the over-expression of EGF receptor is related with fibrous, colorectal, cervical and gastric tumorigenesis. We fabricated the capacitance sensor with a gap area of 50 μm × 200 μm by using photolithography and lift-off method. Using the capacitance sensor, we investigated the time dependent capacitance changes of different kinds of fibrous cells, such as HT1080 fibrosarcoma, L-929 fibroblast cell line and nHDF dermal fibroblast primary cell. We found that when we put the EGF, the capacitance decreased due to the immobilization of EGF to EGF receptor on the cell membrane. The quantitative determination of EGF receptor level for various fibrous cells was carried out and the results showed good correlation with conventional method. Based on our results, we suggest that the capacitance sensor can measure the expression level of the EGF receptor on cell membrane and be a good candidate as a cancer diagnosis.

Detection of novel polymorphisms in the ckit gene of canine patients with lymphoma, melanoma, haemangiosarcoma, and osteosarcoma.

PubMed

Gramer, Irina; Kessler, Martin; Geyer, Joachim

2016-06-01

Tyrosine kinase inhibitors (TKIs) that specifically target cKIT represent a therapeutic approach for non-resectable canine mast cell tumours (MCTs) grade II/III. The therapeutic benefit of TKIs has been investigated in other tumours based on clinical response rates and identification of gain-of-function mutations. In the present study, cKIT expression in 14 dogs with osteosarcoma, melanoma, haemangiosarcoma, lymphoma, and fibrosarcoma was analysed. Tissue samples were used for cKIT sequencing to (I) detect the cKIT transcript and to (II) identify gain-of-function mutations. The cKIT transcript was detected in ten patients. Four novel amino acid substitutions and five silent polymorphisms were identified. Furthermore, an insertion mutation (GNSK) was discovered in the tissue, but not in the blood sample of one dog. CKIT expression was identified in a variety of canine tumours and, therefore, TKIs might have a broader therapeutic indication apart from treatment of MCTs. Further investigations will be necessary to localize the cKIT protein in the respective tumours and to evaluate the functional consequence of the cKIT variants identified in the present study.

A Comparative Evaluation of EPR and OxyLite Oximetry Using a Random Sampling of pO2 in a Murine Tumor

PubMed Central

Vikram, Deepti S.; Bratasz, Anna; Ahmad, Rizwan; Kuppusamy, Periannan

2015-01-01

Methods currently available for the measurement of oxygen concentrations (oximetry) in viable tissues differ widely from each other in their methodological basis and applicability. The goal of this study was to compare two novel methods, particulate-based electron paramagnetic resonance (EPR) and OxyLite oximetry, in an experimental tumor model. EPR oximetry uses implantable paramagnetic particulates, whereas OxyLite uses fluorescent probes affixed on a fiber-optic cable. C3H mice were transplanted with radiation-induced fibrosarcoma (RIF-1) tumors in their hind limbs. Lithium phthalocyanine (LiPc) microcrystals were used as EPR probes. The pO2 measurements were taken from random locations at a depth of ~3 mm within the tumor either immediately or 48 h after implantation of LiPc. Both methods revealed significant hypoxia in the tumor. However, there were striking differences between the EPR and OxyLite readings. The differences were attributed to the volume of tissue under examination and the effect of needle invasion at the site of measurement. This study recognizes the unique benefits of EPR oximetry in terms of robustness, repeatability and minimal invasiveness. PMID:17705635

Generation of glucose-sensitive insulin-secreting beta-like cells from human embryonic stem cells by incorporating a synthetic lineage-control network.

PubMed

Saxena, Pratik; Bojar, Daniel; Zulewski, Henryk; Fussenegger, Martin

2017-10-10

We previously reported novel technology to differentiate induced pluripotent stem cells (IPSCs) into glucose-sensitive insulin-secreting beta-like cells by engineering a synthetic lineage-control network regulated by the licensed food additive vanillic acid. This genetic network was able to program intricate expression dynamics of the key transcription factors Ngn3 (neurogenin 3, OFF-ON-OFF), Pdx1 (pancreatic and duodenal homeobox 1, ON-OFF-ON) and MafA (V-maf musculoaponeurotic fibrosarcoma oncogene homologue A, OFF-ON) to guide the differentiation of IPSC-derived pancreatic progenitor cells to beta-like cells. In the present study, we show for the first time that this network can also program the expression dynamics of Ngn3, Pdx1 and MafA in human embryonic stem cell (hESC)-derived pancreatic progenitor cells and drive differentiation of these cells into glucose-sensitive insulin-secreting beta-like cells. Therefore, synthetic lineage-control networks appear to be a robust methodology for differentiating pluripotent stem cells into somatic cell types for basic research and regenerative medicine. Copyright © 2017 Elsevier B.V. All rights reserved.

Macroscopic singlet oxygen model incorporating photobleaching as an input parameter

NASA Astrophysics Data System (ADS)

Kim, Michele M.; Finlay, Jarod C.; Zhu, Timothy C.

2015-03-01

A macroscopic singlet oxygen model for photodynamic therapy (PDT) has been used extensively to calculate the reacted singlet oxygen concentration for various photosensitizers. The four photophysical parameters (ξ, σ, β, δ) and threshold singlet oxygen dose ([1O2]r,sh) can be found for various drugs and drug-light intervals using a fitting algorithm. The input parameters for this model include the fluence, photosensitizer concentration, optical properties, and necrosis radius. An additional input variable of photobleaching was implemented in this study to optimize the results. Photobleaching was measured by using the pre-PDT and post-PDT sensitizer concentrations. Using the RIF model of murine fibrosarcoma, mice were treated with a linear source with fluence rates from 12 - 150 mW/cm and total fluences from 24 - 135 J/cm. The two main drugs investigated were benzoporphyrin derivative monoacid ring A (BPD) and 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a (HPPH). Previously published photophysical parameters were fine-tuned and verified using photobleaching as the additional fitting parameter. Furthermore, photobleaching can be used as an indicator of the robustness of the model for the particular mouse experiment by comparing the experimental and model-calculated photobleaching ratio.

[The Role of Membrane-Bound Heat Shock Proteins Hsp90 in Migration of Tumor Cells in vitro and Involvement of Cell Surface Heparan Sulfate Proteoglycans in Protein Binding to Plasma Membrane].

PubMed

Snigireva, A V; Vrublevskaya, V V; Skarga, Y Y; Morenkov, O S

2016-01-01

Heat shock protein Hsp90, detected in the extracellular space and on the membrane of cells, plays an important role in cell motility, migration, invasion and metastasis of tumor cells. At present, the functional role and molecular mechanisms of Hsp90 binding to plasma membrane are not elucidated. Using isoform-specific antibodies against Hsp90, Hsp9α and Hsp90β, we showed that membrane-bound Hsp90α and Hsp90β play a significant role in migration of human fibrosarcoma (HT1080) and glioblastoma (A-172) cells in vitro. Disorders of sulfonation of cell heparan sulfates, cleavage of cell heparan. sulfates by heparinase I/III as well as treatment of cells with heparin lead to an abrupt reduction in the expression level of Hsp90 isoforms. Furthermore, heparin significantly inhibits tumor cell migration. The results obtained demonstrate that two isoforms of membrane-bound Hsp90 are involved in migration of tumor cells in vitro and that cell surface heparan sulfate proteoglycans play a pivotal role in the "anchoring" of Hsp90α and Hsp90β to the plasma membrane.

A systems biology approach to overcome TRAIL resistance in cancer treatment.

PubMed

Selvarajoo, Kumar

2017-09-01

Over the last decade, our research team has investigated the dynamic responses and global properties of living cells using systems biology approaches. More specifically, we have developed computational models and statistical techniques to interpret instructive cell signaling and high-throughput transcriptome-wide behaviors of immune, cancer, and embryonic development cells. Here, I will focus on our recent works in overcoming cancer resistance. TRAIL (tumor necrosis factor related apoptosis-inducing ligand), a proinflammatory cytokine, has shown promising success in controlling cancer threat due to its ability to induce apoptosis in cancers specifically, while having limited effect on normal cells. Nevertheless, several malignant cancer types, such as fibrosarcoma (HT1080) or colorectal adenocarcinoma (HT29), remain non-sensitive to TRAIL. To sensitize HT1080 to TRAIL treatment, we first developed a dynamic computational model based on perturbation-response approach, to predict a crucial co-target to enhance cell death. The model simulations suggested that PKC inhibition together with TRAIL induce 95% cell death. Subsequently, we confirmed this result experimentally utilizing the PKC inhibitor, bisindolylmaleimide (BIM) I, and PKC siRNAs in HT1080. Copyright © 2017 Elsevier Ltd. All rights reserved.

A Highly Sensitive Biocompatible Spin Probe for Imaging of Oxygen Concentration in Tissues

PubMed Central

Bratasz, Anna; Kulkarni, Aditi C.; Kuppusamy, Periannan

2007-01-01

The development of an injectable probe formulation, consisting of perchlorotriphenylmethyl triester radical dissolved in hexafluorobenzene, for in vivo oximetry and imaging of oxygen concentration in tissues using electron paramagnetic resonance (EPR) imaging is reported. The probe was evaluated for its oxygen sensitivity, biostability, and distribution in a radiation-induced fibrosarcoma tumor transplanted into C3H mice. Some of the favorable features of the probe are: a single narrow EPR peak (anoxic linewidth, 41 μT), high solubility in hexafluorobenzene (>12 mM), large linewidth sensitivity to molecular oxygen (∼1.8 μT/mmHg), good stability in tumor tissue (half-life: 3.3 h), absence of spin-spin broadening (up to 12 mM), and lack of power saturation effects (up to 200 mW). Three-dimensional spatial and spectral-spatial (spectroscopic) EPR imaging measurements were used to visualize the distribution of the probe, as well as to obtain spatially resolved pO2 information in the mice tumor subjected to normoxic and hyperoxic treatments. The new probe should enable unique opportunities for measurement of the oxygen concentration in tumors using EPR methods. PMID:17259268

Tumours of the upper alimentary tract

PubMed Central

Head, K. W.

1976-01-01

Tumours of the oropharynx of domestic animals are common in most parts of the world, but squamous cell carcinoma of the upper alimentary tract shows differences in prevalence in different geographical areas and occurs at different sites in the various species. Oral tumours of the melanogenic system are more common in dogs than in man. The following main histological categories, which broadly correspond to those used in the classification of tumours of man, are described: papilloma; squamous cell carcinoma; salivary gland tumours; malignant melanoma; tumours of soft (mesenchymal) tissues; tumours of the facial bones; tumours of haematopoietic and related tissues; and odontogenic tumours and jaw cysts. Papilloma, squamous cell carcinoma, malignant melanoma, fibroma, and fibrosarcoma account for about 80% of the tumours that occur in the upper alimentary tract of domestic animals. ImagesFig. 6Fig. 7Fig. 8Fig. 9Fig. 34Fig. 35Fig. 36Fig. 37Fig. 2Fig. 3Fig. 4Fig. 5Fig. 22Fig. 23Fig. 24Fig. 25Fig. 26Fig. 27Fig. 28Fig. 29Fig. 14Fig. 15Fig. 16Fig. 17Fig. 30Fig. 31Fig. 32Fig. 33Fig. 18Fig. 19Fig. 20Fig. 21Fig. 10Fig. 11Fig. 12Fig. 13Fig. 1 PMID:1086147

Principles of treatment for soft tissue sarcoma.

PubMed

Dernell, W S; Withrow, S J; Kuntz, C A; Powers, B E

1998-02-01

Soft tissue sarcomas (STS) are mesenchymal tumors arising from connective tissue elements and are grouped together based on a common biologic behavior. The most common histologic types include malignant peripheral nerve sheath tumors (schwannoma and neurofibrosarcoma) "hemangiopericytoma," fibrosarcoma, and malignant fibrous histiocytoma. These tumors are relatively slow growing yet locally invasive with a high rate of recurrence following conservative management. Appropriate preoperative planning and aggressive surgical resection often result in long-term remission or cure. Identification and evaluation of resection margins are paramount in appropriate case management. The addition of radiotherapy after surgical resection can aid in remission for incompletely resected masses. Systemic chemotherapy for STS should be considered for high-grade tumors with a moderate metastatic potential. Potential prognostic factors include grade, resection margins, size, location, histologic type, and previous treatment, with grade and margins being the most important. Tumor types classified as STS that differ slightly in their presentation or treatment, including synovial cell sarcoma, rhabdomyosarcoma, liposarcoma, and vaccine-associated STS in cats, are discussed. Soft tissue sarcomas can be a frustrating disease to treat, but adherence to solid surgical oncology principles can greatly increase the odds of good disease control.

A fine structure genomic map of the region of 12q13 containing SAS and CDK4

DOE Office of Scientific and Technical Information (OSTI.GOV)

Linder, C.Y.; Elkahloun, A.G.; Su, Y.A.

1994-09-01

We have recently adapted a method, originally described by Rackwitz, to the rapid restriction mapping of multiple cosmid DNA samples. Linearization of the cosmids at the lambda cohesive site using lambda terminase is followed by partial digestion with selected restriction enzymes and hybridization to oligonucleotides specific for the right or left hand termini. Partial digestions are performed in a microtiter plate thus allowing up to 12 cosmid clones to be digested with one restriction enzyme. We have applied this rapid restriction mapping method to cosmids derived from a region of chromosome 12q13 that has recently been shown to be amplifiedmore » in a variety of cancers including malignant fibrous histiocytoma, fibrosarcoma, liposarcoma, osteosarcoma and brain tumors. A small segment of this amplification unit containing three genes, SAS (a membrane protein), CDK4 (a cyclin dependent kinase) and OS-9 (a recently described cDNA) has been analyzed with the system described above. This fine structure genomic map will be useful for completing the expression map of this region as well as characterizing its pattern of amplification in tumor specimens.« less

A Clinicopathological Analysis of Soft Tissue Sarcoma with Telangiectatic Changes.

PubMed

Kobayashi, Hiroshi; Ae, Keisuke; Tanizawa, Taisuke; Gokita, Tabu; Motoi, Noriko; Matsumoto, Seiichi

2015-01-01

Background. Soft tissue sarcoma with a hemorrhagic component that cannot be easily diagnosed by needle biopsy is defined here as soft tissue sarcoma with telangiectatic changes (STST). Methods. We retrospectively reviewed clinicopathological data of STST from 14 out of 784 patients (prevalence: 1.8%) with soft tissue sarcoma. Results. Tumors were found mostly in the lower leg. Histological diagnoses were undifferentiated pleomorphic sarcoma (n = 5), synovial sarcoma (n = 5), epithelioid sarcoma (n = 2), and malignant peripheral nerve sheath tumor and fibrosarcoma (n = 1). No history of trauma to the tumor site was recorded in any patient. Needle aspiration transiently reduced the tumor volume, but subsequent recovery of tumor size was observed in all cases. Out of 14 patients, 9 presented with a painful mass. MRI characteristics included intratumoral nodules (64.3%). The local recurrence rate was 14.3%, and the 2-year event-free survival rate was poorer (50%) than that of most sarcomas. Conclusions. STST is unique in its clinicopathological presentation. Painful hematomas without a trauma history, intratumoral nodules within a large hemorrhagic component, and subsequent recovery of tumor size after aspiration are indicative of the presence of STST.

A Clinicopathological Analysis of Soft Tissue Sarcoma with Telangiectatic Changes

PubMed Central

Kobayashi, Hiroshi; Ae, Keisuke; Tanizawa, Taisuke; Gokita, Tabu; Motoi, Noriko; Matsumoto, Seiichi

2015-01-01

Background. Soft tissue sarcoma with a hemorrhagic component that cannot be easily diagnosed by needle biopsy is defined here as soft tissue sarcoma with telangiectatic changes (STST). Methods. We retrospectively reviewed clinicopathological data of STST from 14 out of 784 patients (prevalence: 1.8%) with soft tissue sarcoma. Results. Tumors were found mostly in the lower leg. Histological diagnoses were undifferentiated pleomorphic sarcoma (n = 5), synovial sarcoma (n = 5), epithelioid sarcoma (n = 2), and malignant peripheral nerve sheath tumor and fibrosarcoma (n = 1). No history of trauma to the tumor site was recorded in any patient. Needle aspiration transiently reduced the tumor volume, but subsequent recovery of tumor size was observed in all cases. Out of 14 patients, 9 presented with a painful mass. MRI characteristics included intratumoral nodules (64.3%). The local recurrence rate was 14.3%, and the 2-year event-free survival rate was poorer (50%) than that of most sarcomas. Conclusions. STST is unique in its clinicopathological presentation. Painful hematomas without a trauma history, intratumoral nodules within a large hemorrhagic component, and subsequent recovery of tumor size after aspiration are indicative of the presence of STST. PMID:26839509

Giant fibrosarcoma prostuberans of abodominal wall: management problems in resources-constrained country.

PubMed

Chukwuanukwu, T O G; Anyanwu, S N C

2009-09-01

Abdominal wall sarcomas represent less than 1% of adult malignancies. Dermatofibrosarcoma protuberans can grow to very large sizes and the recommended resection 2-3 cm from the macroscopic tumour margin can produce very large full thickness defects of the abdominal wall. Reconstruction of such defects can be quite challenging in resource constrained areas where patients present late with giant lesions. To highlight the presentation and management challenges faced by the surgical oncologist and reconstructive surgeon in a resource constrained country when faced with giant Dermatofibrosarcoma protuberans of the abdominal wall. Prospective study of patients with abdominal wall soft tissue sarcoma presenting to the authors. Cases of giant dermatofibrosarcoma protuberns who underwent surgery were analysed. Seven cases managed over an eight year period (January 2000 to December 2007). Age ranged from 27-70 yrs with slight female preponderance 1.5:1 F:M. Three presented with recurrent fungating masses. Only one could be reconstructed with prolene mesh. One recurrence was noted during the period under study. Poverty, ignorance and lack of necessary working tools are major challenges faced by the surgical oncologist and reconstructive surgeon in resource constrained areas and pose a major obstacle to the control of cancer in these areas.

Alternative site of implantation affects tumor malignancy and metastatic potential in mice: its comparison to the flank model.

PubMed

Speroni, Lucia; Bustuoabad, Victoria de Los Angeles; Gasparri, Julieta; Chiaramoni, Nadia Silvia; Taira, María Cristina; Ruggiero, Raúl Alejandro; Alonso, Silvia Del Valle

2009-02-01

MC-C fibrosarcoma and B16F0 melanoma tumors were implanted intradermally in the dorsal region of the foot of mice. Tumor progression was compared to standard implantation in the flank. Although foot tumors only reached 13% (MC-C) and 25% (B16F0) of the mean volume of flank tumors, a more malignant phenotype in terms of histology and survival rate was observed in this type of tumors. Moreover, lung metastases were only detected in hosts bearing foot tumors, in contrast to MC-C and B16F0 populations with tumors growing in the flank. In addition, cellular influx and local immune reaction were higher in the dorsal region of the foot. According to our results, the dermis of the flank allows excessive tumor growth due to its low reactivity. Thus, differences in innate and adaptive immune effectors between the evaluated tumor microenvironments would account for the differences in tumor malignancy. Due to its striking differences with the standard flank inoculation, the tumor implantation model herein introduced could be a valuable tool to study the metastatic potential of different cell lines and the microenvironment components affecting tumor growth.

Effective internalization of U251-MG-secreted exosomes into cancer cells and characterization of their lipid components.

PubMed

Toda, Yuki; Takata, Kazuyuki; Nakagawa, Yuko; Kawakami, Hikaru; Fujioka, Shusuke; Kobayashi, Kazuya; Hattori, Yasunao; Kitamura, Yoshihisa; Akaji, Kenichi; Ashihara, Eishi

2015-01-16

Exosomes, the natural vehicles of various biological molecules, have been examined in several research fields including drug delivery. Although understanding of the biological functions of exosomes has increased, how exosomes are transported between cells remains unclear. We hypothesized that cell tropism is important for effective exosomal intercellular communication and that parental cells regulate exosome movement by modulating constituent exosomal molecules. Herein, we demonstrated the strong translocation of glioblastoma-derived exosomes (U251exo) into their parental (U251) cells, breast cancer (MDA-MB-231) cells, and fibrosarcoma (HT-1080). Furthermore, disruption of proteins of U251exo by enzymatic treatment did not affect their uptake. Therefore, we focused on lipid molecules of U251exo with the expectation that they are crucial for effective incorporation of U251exo by cancer cells. Phosphatidylethanolamine was identified as a unique lipid component of U251-MG cell-derived extracellular vesicles. From these results, valuable insight is provided into the targeting of U251exo to cancer cells, which will help to develop a cancer-targeted drug delivery system. Copyright © 2014 Elsevier Inc. All rights reserved.

Dynamic quantitative proteomics characterization of TNF-α-induced necroptosis.

PubMed

Wang, Yang; Huang, Zhi-Hao; Li, Yang-Jia; He, Gui-Wei; Yu, Ru-Yuan; Yang, Jie; Liu, Wan-Ting; Li, Bin; He, Qing-Yu

2016-12-01

Emerging evidence suggested that necroptosis has essential functions in many human inflammatory diseases, but the molecular mechanisms of necroptosis remain unclear. Here, we employed SILAC quantitatively dynamic proteomics to compare the protein changes during TNF-α-induced necroptosis at different time points in murine fibrosarcoma L929 cells with caspase-8 deficiency, and then performed the systematical analysis on the signaling networks involved in the progress using bioinformatics methods. Our results showed that a total of 329, 421 and 378 differentially expressed proteins were detected at three stages of necroptosis, respectively. Gene ontology and ingenuity pathway analysis (IPA) revealed that the proteins regulated at early stages of necroptosis (2, 6 h) were mainly involved in mitochondria dysfunction, oxidative phosphorylation and Nrf-2 signaling, while the expression levels of the proteins related to ubiquitin, Nrf-2, and NF-κB pathways were found to have changes at last stages of necroptosis (6, 18 h). Taken together, we demonstrated for the first time that dysfunction of mitochondria and ubiquitin-proteasome signaling contributed to the initiation and execution of necroptosis. These findings may provide clues for the identification of important regulators in necroptosis and the development of novel therapeutic strategies for the related diseases.

Multifunctional biosynthesized silver nanoparticles exhibiting excellent antimicrobial potential against multi-drug resistant microbes along with remarkable anticancerous properties.

PubMed

Jha, Diksha; Thiruveedula, Prasanna Kumar; Pathak, Rajiv; Kumar, Bipul; Gautam, Hemant K; Agnihotri, Shrish; Sharma, Ashwani Kumar; Kumar, Pradeep

2017-11-01

This study demonstrates the therapeutic potential of silver nanoparticles (AgNPs), which were biosynthesized using the extracts of Citrus maxima plant. Characterization through UV-Vis spectrophotometry, Dynamic Light Scattering (DLS), Fourier Transform Infrared spectroscopy (FTIR), X-ray Diffraction (XRD) and Transmission Electron Microscopy (TEM) confirmed the formation of AgNps in nano-size range. These nanoparticles exhibited enhanced antioxidative activity and showed commendable antimicrobial activity against wide range of microbes including multi-drug resistant bacteria that were later confirmed by TEM. These particles exhibited minimal toxicity when cytotoxicity study was performed on normal human lung fibroblast cell line as well as human red blood cells. It was quite noteworthy that these particles showed remarkable cytotoxicity on human fibrosarcoma and mouse melanoma cell line (B16-F10). Additionally, the apoptotic topographies of B16-F10 cells treated with AgNps were confirmed by using acridine orange and ethidium bromide dual dye staining, caspase-3 assay, DNA fragmentation assay followed by cell cycle analysis using fluorescence-activated cell sorting. Taken together, these results advocate promising potential of the biosynthesized AgNps for their use in therapeutic applications. Copyright © 2017 Elsevier B.V. All rights reserved.

Acquired pulmonary artery stenosis in four dogs.

PubMed

Scansen, Brian A; Schober, Karsten E; Bonagura, John D; Smeak, Daniel D

2008-04-15

4 dogs with acquired pulmonary artery stenosis (PAS) were examined for various clinical signs. One was a mixed-breed dog with congenital valvular PAS that subsequently developed peripheral PAS, one was a Golden Retriever with pulmonary valve fibrosarcoma, one was a Pembroke Welsh Corgi in which the left pulmonary artery had inadvertently been ligated during surgery for correction of patent ductus arteriosus, and one was a Boston Terrier with a heart-base mass compressing the pulmonary arteries. All 4 dogs were evaluated with 2-dimensional and Doppler echocardiography to characterize the nature and severity of the stenoses; other diagnostic tests were also performed. The mixed-breed dog with valvular and peripheral PAS was euthanized, surgical resection of the pulmonic valve mass was performed in the Golden Retriever, corrective surgery was performed on the Pembroke Welsh Corgi with left pulmonary artery ligation, and the Boston Terrier with the heart-base mass was managed medically. Acquired PAS in dogs may manifest as a clinically silent heart murmur, syncope, or right-sided heart failure. The diagnosis is made on the basis of imaging findings, particularly results of 2-dimensional and Doppler echocardiography. Treatment may include surgical, interventional, or medical modalities and is targeted at resolving the inciting cause.

Evolutionarily Repurposed Networks Reveal the Well-Known Antifungal Drug Thiabendazole to Be a Novel Vascular Disrupting Agent

PubMed Central

Cha, Hye Ji; Byrom, Michelle; Mead, Paul E.; Ellington, Andrew D.; Wallingford, John B.; Marcotte, Edward M.

2012-01-01

Studies in diverse organisms have revealed a surprising depth to the evolutionary conservation of genetic modules. For example, a systematic analysis of such conserved modules has recently shown that genes in yeast that maintain cell walls have been repurposed in vertebrates to regulate vein and artery growth. We reasoned that by analyzing this particular module, we might identify small molecules targeting the yeast pathway that also act as angiogenesis inhibitors suitable for chemotherapy. This insight led to the finding that thiabendazole, an orally available antifungal drug in clinical use for 40 years, also potently inhibits angiogenesis in animal models and in human cells. Moreover, in vivo time-lapse imaging revealed that thiabendazole reversibly disassembles newly established blood vessels, marking it as vascular disrupting agent (VDA) and thus as a potential complementary therapeutic for use in combination with current anti-angiogenic therapies. Importantly, we also show that thiabendazole slows tumor growth and decreases vascular density in preclinical fibrosarcoma xenografts. Thus, an exploration of the evolutionary repurposing of gene networks has led directly to the identification of a potential new therapeutic application for an inexpensive drug that is already approved for clinical use in humans. PMID:22927795

SUMOylated MAFB promotes colorectal cancer tumorigenesis

PubMed Central

Xie, Yin-Yin; Sun, Xiao-Jian; Zhao, Ren; Huang, Qiu-Hua

2016-01-01

The transcription factor, v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog B (MAFB), promotes tumorigenesis in some cancers. In this study, we found that MAFB levels were increased in clinical colorectal cancer (CRC) samples, and higher expression correlated with more advanced TNM stage. We identified MAFB amplifications in a majority of tumor types in an assessment of The Cancer Genome Atlas database. Altered MAFB levels due to gene amplification, deletion, mutation, or transcription upregulation occurred in 9% of CRC cases within the database. shRNA knockdown experiments demonstrated that MAFB deficiency blocked CRC cell proliferation by arresting the cell cycle at G0/G1 phase in vitro. We found that MAFB could be SUMOylated by SUMO1 at lysine 32, and this modification was critical for cell cycle regulation by MAFB in CRC cells. SUMOylated MAFB directly regulated cyclin-dependent kinase 6 transcription by binding to its promoter. MAFB knockdown CRC cell xenograft tumors in mice grew more slowly than controls, and wild-type MAFB-overexpressing tumors grew more quickly than tumors overexpressing MAFB mutated at lysine 32. These data suggest that SUMOylated MAFB promotes CRC tumorigenesis through cell cycle regulation. MAFB and its SUMOylation process may serve as novel therapeutic targets for CRC treatment. PMID:27829226

Low concentrations of alendronate increase the local invasive potential of osteoblastic sarcoma cell lines via connexin 43 activation.

PubMed

Yoshitani, Kazuhiro; Kido, Akira; Honoki, Kanya; Akahane, Manabu; Fujii, Hiromasa; Tanaka, Yasuhito

2011-07-15

Bisphosphonates (BPs) are agents used for treating disorders of excessive bone resorption. In addition, due to their cell-killing activity, BPs were potent candidates for adjuvant cancer therapy. On the other hand, low-concentrations of BPs have been reported to increase cellular viability in several types of tumor cells. Therefore, we focused on the effect of BPs on cellular aggressiveness of malignant bone tumors at low concentrations. MTS assay was performed using osteosarcoma cell lines MG63 and HOS, fibrosarcoma cell line HT1080, and prostate cancer cell line PC3. All the cell lines showed toxicity at high concentrations. On the other hand, at lower concentrations, the cellular viabilities of HOS and MG63 were rather higher than those of untreated controls. Since this tendency was most evident, HOS was used for further assays, including cellular motility, bone resorption activity, and cathepsin K activity. The low-concentration of alendronate enhanced cellular viability and motility, which correlated with the expression of connexin 43 at the mRNA and protein levels. Interestingly, oleamide, a potent connexin 43 inhibitor, had an inhibitory effect on the enhanced proliferation. Our data suggest that alendronate may enhance the proliferation of osteoblastic cell line through connexin 43 activation. Copyright © 2011 Elsevier GmbH. All rights reserved.

Zinc oxide nanoparticles as novel alpha-amylase inhibitors

NASA Astrophysics Data System (ADS)

Dhobale, Sandip; Thite, Trupti; Laware, S. L.; Rode, C. V.; Koppikar, Soumya J.; Ghanekar, Ruchika-Kaul; Kale, S. N.

2008-11-01

Amylase inhibitors, also known as starch blockers, contain substances that prevent dietary starches from being absorbed by the body via inhibiting breakdown of complex sugars to simpler ones. In this sense, these materials are projected as having potential applications in diabetes control. In this context, we report on zinc oxide nanoparticles as possible alpha-amylase inhibitors. Zinc oxide nanoparticles have been synthesized using soft-chemistry approach and 1-thioglycerol was used as a surfactant to yield polycrystalline nanoparticles of size ˜18 nm, stabilized in wurtzite structure. Conjugation study and structural characterization have been done using x-ray diffraction technique, Fourier transform infrared spectroscopy, UV-visible spectroscopy, and transmission electron microscopy. Cytotoxicity studies on human fibrosarcoma (HT-1080) and skin carcinoma (A-431) cell lines as well as mouse primary fibroblast cells demonstrate that up to a dose of 20 μg/ml, ZnO nanoparticles are nontoxic to the cells. We report for the first time the alpha-amylase inhibitory activity of ZnO nanoparticles wherein an optimum dose of 20 μg/ml was sufficient to exhibit 49% glucose inhibition at neutral pH and 35 °C temperature. This inhibitory activity was similar to that obtained with acarbose (a standard alpha-amylase inhibitor), thereby projecting ZnO nanoparticles as novel alpha-amylase inhibitors.

Appropriate therapy for type 2 diabetes mellitus in view of pancreatic β-cell glucose toxicity: "the earlier, the better".

PubMed

Kaneto, Hideaki; Matsuoka, Taka-Aki; Kimura, Tomohiko; Obata, Atsushi; Shimoda, Masashi; Kamei, Shinji; Mune, Tomoatsu; Kaku, Kohei

2016-03-01

Pancreatic β-cells secrete insulin when blood glucose levels become high; however, when β-cells are chronically exposed to hyperglycemia, β-cell function gradually deteriorates, which is known as β-cell glucose toxicity. In the diabetic state, nuclear expression of the pancreatic transcription factors pancreatic and duodenal homeobox 1 (PDX-1) and v-Maf musculoaponeurotic fibrosarcoma oncogene family, protein A (MafA) is decreased. In addition, incretin receptor expression in β-cells is decreased, which is likely involved in the impairment of incretin effects in diabetes. Clinically, it is important to select appropriate therapy for type 2 diabetes mellitus (T2DM) so that β-cell function can be preserved. In addition, when appropriate pharmacological interventions against β-cell glucose toxicity are started at the early stages of diabetes, β-cell function is substantially restored, which is not observed if treatment is started at advanced stages. These observations indicate that it is likely that downregulation of pancreatic transcription factors and/or incretin receptors is involved in β-cell dysfunction observed in T2DM and it is very important to start appropriate pharmacological intervention against β-cell glucose toxicity in the early stages of diabetes. © 2015 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

Expression of the Intermediate Filament Nestin in Gastrointestinal Stromal Tumors and Interstitial Cells of Cajal

PubMed Central

Tsujimura, Tohru; Makiishi-Shimobayashi, Chiaki; Lundkvist, Johan; Lendahl, Urban; Nakasho, Keiji; Sugihara, Ayako; Iwasaki, Teruo; Mano, Masayuki; Yamada, Naoko; Yamashita, Kunihiro; Toyosaka, Akihiro; Terada, Nobuyuki

2001-01-01

It has recently been proposed that gastrointestinal stromal tumors (GISTs) originate from stem cells that differentiate toward a phenotype of interstitial cells of Cajal (ICCs). Nestin is a newly identified intermediate filament protein, and is predominantly expressed in immature cells, such as neuroectodermal stem cells and skeletal muscle progenitor cells, and tumors originating from these cells. In this study, we examined, using immunohistochemistry, the nestin expression in GISTs and ICCs to clarify the origin of GISTs. Strong immunoreactivity for nestin was observed in all 18 GISTs, and its expression was confirmed by Western blot and Northern blot analyses. In contrast, three leiomyomas and a schwannoma that developed in the gastrointestinal tract showed no apparent immunoreactivity for nestin. Among 17 mesenchymal tumors (seven leiomyosarcomas, five malignant peripheral nerve sheath tumors, and five fibrosarcomas) that occurred in sites other than the gastrointestinal tract, only two malignant peripheral nerve sheath tumors were moderately immunoreactive for nestin. Furthermore, with fluorescence double immunostaining of the normal small intestine, nestin expression was demonstrated in ICCs. These results show that nestin may be a useful marker for diagnosis of GISTs, and support the current hypothesis that GISTs are tumors of stem cells that differentiate toward an ICC phenotype. PMID:11238030

Spectroellipsometric, AFM and XPS probing of stainless steel surfaces subjected to biological influences

NASA Astrophysics Data System (ADS)

Vinnichenko, M.; Chevolleau, Th; Pham, M. T.; Poperenko, L.; Maitz, M. F.

2002-11-01

Surface modification of austenitic stainless steel (SS) 316L after incubation in growing cell cultures and cell-free media as control has been studied. The following treatments were applied: mouse fibrosarcoma cells L929 for 3 and 7 days, polymorphonuclear neutrophils for 3 and 7 days and human osteosarcoma cells SAOS-2 for 7 and 14 days. Cells were enzymatically removed in all cases. The modified surfaces were probed in comparison with untreated ones by means of spectroscopic ellipsometry (SE), X-ray photoelectron spectroscopy (XPS) and atomic force microscopy (AFM). XPS shows the appearance of the peak of bonded nitrogen at 400.5 eV characteristic for adsorbed proteins on the surface for each type of cells and for the cell-free medium. Migration of Ni in the adsorbed layer is observed in all cases for samples after the cell cultures. The protein layer thickness is ellipsometrically determined to be within 2.5-6.0 nm for all treated samples with parameterization of its optical constants in Cauchy approach. The study showed that for such biological treatments of the SS the protein layer adsorption is the dominating process in the first 2 weeks, which could play a role in the process of corrosion by complex forming properties with metal ions.

Immunohistochemical characterization of hemangiopericytomas and other spindle cell tumors in the dog.

PubMed

Pérez, J; Bautista, M J; Rollón, E; de Lara, F C; Carrasco, L; Martin de las Mulas, J

1996-07-01

The immunohistochemical expression of muscle actin has been studied in 45 canine hemangiopericytomas (CHP) using a monoclonal antibody (HHF35) and formalin-fixed, paraffin-embedded specimens. The distribution of vimentin, desmin, cytokeratins, lysozyme, factor VIII-related antigen, S-100 protein, and glial fibrillary acidic protein was studied both in CHP and in some canine soft-tissue neoplasms (seven fibrosarcomas, seven benign schwannomas, seven benign fibrous histiocytomas, and six leiomyosarcomas) used as controls for differential diagnosis. All CHP and control tumors expressed vimentin. Twenty-three CHP expressed muscle actin, whereas all control tumors analyzed were muscle actin-negative, with the exception of leiomyosarcomas. Among muscle actin- and vimentin-positive CHP, one case could be reclassified as leiomyosarcoma because it was desmin-positive, two cases expressed lysozyme, and nine cases expressed S-100 protein. Among muscle actin-negative and vimentin-positive CHP, seven expressed S-100 protein. In addition, S-100 protein was detected in five schwannomas. All CHP and control tumors analyzed were negative for cytokeratins, factor VIII-related antigen, and glial fibrillary acidic protein. Our results support the hypothesis of a pericytic origin of CHP, and suggest that muscle actin, desmin, vimentin, and lysozyme could be useful for the differential diagnosis of canine spindle cell tumors, but not all these neoplasms can be identified with these tumor tissue markers.

Quantitative morphology in canine cutaneous soft tissue sarcomas.

PubMed

Simeonov, R; Ananiev, J; Gulubova, M

2015-12-01

Stained cytological specimens from 24 dogs with spontaneous soft tissue sarcomas [fibrosarcoma (n = 8), liposarcoma (n = 8) and haemangiopericytoma (n = 8)], and 24 dogs with reactive connective tissue lesions [granulation tissue (n = 12) and dermal fibrosis (n = 12)] were analysed by computer-assisted nuclear morphometry. The studied morphometric parameters were: mean nuclear area (MNA; µm(2)), mean nuclear perimeter (MNP; µm), mean nuclear diameter (MND mean; µm), minimum nuclear diameter (Dmin; µm) and maximum nuclear diameter (Dmax; µm). The study aimed to evaluate (1) possibility for quantitative differentiation of soft tissue sarcomas from reactive connective tissue lesions and (2) by using cytomorphometry, to differentiate the various histopathological soft tissue sarcomas subtypes in dogs. The mean values of all nuclear cytomorphometric parameters (except for Dmax) were statistically significantly higher in reactive connective tissue processes than in soft tissue sarcomas. At the same time, however, there were no considerable differences among the different sarcoma subtypes. The results demonstrated that the quantitative differentiation of reactive connective tissue processes from soft tissue sarcomas in dogs is possible, but the same was not true for the different canine soft tissue sarcoma subtypes. Further investigations on this topic are necessary for thorough explication of the role of quantitative morphology in the diagnostics of mesenchymal neoplasms and tumour-like fibrous lesions in dogs. © 2014 John Wiley & Sons Ltd.

A well-known lesion in an unusual location: infantile myofibroma of the eyelid: a case report and review of literature.

PubMed

Asadi Amoli, Fahimeh; Sina, Amir Hossein; Kasai, Aboulfazl; Ayan, Zahra

2010-01-01

Myofibroma is a neoplasia of myofibroblasts that can be solitary or multiple and it is found most commonly in the head & neck region including scalp, forehead, parotid region and oral cavity. In the eyelid it is rarely reported. It has a benign course in the solitary form and fatal in its multiple form. A 4 month male infant referred to Farabi hospital -the referral center for eye diseases- with a 2 month history of a mass in his eyelid with gradual enlargement with no other complaints. The only abnormal physical finding was a 2.5 cm mass in the eyelid. This mass was excised and sent to the hospital pathology laboratory. When confronting a spindle cell lesion with a nodular or multinodular growth pattern which appears biphasic due to alteration of light and dark staining areas, the surgical pathologist should think to the possibility of myofibroma. Its pattern of growth and architecture rules out the other differential diagnoses like nodular fasciitis, fibrous histiocytoma, infantile fibromatosis, and peripheral primitive neuroectodermal tumor, mesenchymal chondrosarcoma, malignant hemangiopericytoma, juvenile fibrosarcoma and poorly differentiated synovial sarcoma. In difficult cases immunohistochemical staining is helpful that is Vimentin & Actin positivity & Desmin, CK, EMA & S100 negativity.

Cytotoxic constituents from Brazilian red propolis and their structure-activity relationship.

PubMed

Li, Feng; Awale, Suresh; Tezuka, Yasuhiro; Kadota, Shigetoshi

2008-05-15

Several classes of flavonoids [flavanoids (1-10), flavonol (11), isoflavones (12-18), isoflavanones (19-22), isoflavans (23-26), chalcones (27-30), auronol (31), pterocarpans (32-37), 2-arylbenzofuran (38), and neoflavonoid (39)] and lignans (40-42) isolated from the MeOH extract of Brazilian red propolis were investigated for their cytotoxic activity against a panel of six different cancer cell lines including murine colon 26-L5 carcinoma, murine B16-BL6 melanoma, murine Lewis lung carcinoma, human lung A549 adenocarcinoma, human cervix HeLa adenocarcinoma, and human HT-1080 fibrosarcoma cell lines. Based on the observed results, structure-activity relationships were discussed. Among the tested compounds, 7-hydroxy-6-methoxyflavanone (3) exhibited the most potent activity against B16-BL6 (IC(50), 6.66microM), LLC (IC(50), 9.29microM), A549 (IC(50), 8.63microM), and HT-1080 (IC(50), 7.94microM) cancer cell lines, and mucronulatol (26) against LLC (IC(50), 8.38microM) and A549 (IC(50), 9.9microM) cancer cell lines. These activity data were comparable to those of the clinically used anticancer drugs, 5-fluorouracil and doxorubicin, against the tested cell lines, suggesting that 3 and 26 are the good candidates for future anticancer drug development.

Use of cisplatin-containing biodegradable beads for treatment of cutaneous neoplasia in equidae: 59 cases (2000-2004).

PubMed

Hewes, Christina A; Sullins, Kenneth E

2006-11-15

To determine outcome for equids with cutaneous neoplasms treated with cisplatin-containing biodegradable beads, alone or in conjunction with debulking. Retrospective case series. 56 horses, 1 zebra, 1 donkey, and 1 mule. Medical records were reviewed. Follow-up information was obtained through telephone conversations with owners and trainers of the animals. 22 tumors were sarcoids, 6 were fibrosarcomas, 1 was a fibroma, 2 were peripheral nerve sheath tumors, 11 were squamous cell carcinomas, 14 were melanomas (13 gray horses and 1 bay horse), 1 was a lymphosarcoma, 1 was an adenocarcinoma, and 1 was a basal cell tumor. Forty-five (76%) animals underwent conventional or laser debulking of the tumor prior to bead implantation. Forty of 48 (83%) animals for which long-term follow-up information was available were relapse free 2 years after treatment. This included 20 of 22 animals with spindle cell tumors (including 11/13 horses with sarcoids), 6 of 10 animals with squamous cell carcinomas, 13 of 14 animals with melanomas, and 2 of 3 animals with other tumor types. Adverse effects were minimal. Results suggest that implantation of cisplatin-containing biodegradable beads, with or without tumor debulking, may be an effective treatment for equidae with various cutaneous neoplasms.

Probing the compressibility of tumor cell nuclei by combined atomic force-confocal microscopy

NASA Astrophysics Data System (ADS)

Krause, Marina; te Riet, Joost; Wolf, Katarina

2013-12-01

The cell nucleus is the largest and stiffest organelle rendering it the limiting compartment during migration of invasive tumor cells through dense connective tissue. We here describe a combined atomic force microscopy (AFM)-confocal microscopy approach for measurement of bulk nuclear stiffness together with simultaneous visualization of the cantilever-nucleus contact and the fate of the cell. Using cantilevers functionalized with either tips or beads and spring constants ranging from 0.06-10 N m-1, force-deformation curves were generated from nuclear positions of adherent HT1080 fibrosarcoma cell populations at unchallenged integrity, and a nuclear stiffness range of 0.2 to 2.5 kPa was identified depending on cantilever type and the use of extended fitting models. Chromatin-decondensating agent trichostatin A (TSA) induced nuclear softening of up to 50%, demonstrating the feasibility of our approach. Finally, using a stiff bead-functionalized cantilever pushing at maximal system-intrinsic force, the nucleus was deformed to 20% of its original height which after TSA treatment reduced further to 5% remaining height confirming chromatin organization as an important determinant of nuclear stiffness. Thus, combined AFM-confocal microscopy is a feasible approach to study nuclear compressibility to complement concepts of limiting nuclear deformation in cancer cell invasion and other biological processes.

"Ancient" schwannoma of the submandibular gland: A case report and literature review.

PubMed

Ho, Che-Fang; Wu, Pei-Wen; Lee, Ta-Jen; Huang, Chien-Chia

2017-12-01

Schwannomas are solitary neurogenic tumors that arise from cells of the neural sheath. Ancient schwannoma is a relatively rare variant of schwannoma, characterized by increased cellularity and atypia. These cellular changes could be confusing and make the accurate pathologic diagnosis difficult. A 36-year-old man presented with painless swelling in left submandibular region for more than 2 years. The computed tomography confirmed a well-defined cystic lesion in the left submandibular space, which caused superior and posterior displacement of the left submandibular gland. Surgical excision was performed and the pathology confirmed the diagnosis of ancient schwannoma. To our knowledge, this patient is the second case of primary submandibular ancient schwannoma reported in the literatures. The patient underwent tumor resection and postoperative recovery was uneventful. There were no nerve deficits after the operation. There was no recurrence within 1 year of follow-up. Schwannoma originated from the submandibular gland is extremely rare and only a few cases have been reported. Ancient schwannoma is an even more rare tumor. The increased cellularity and atypia of ancient schwannoma can resemble features of malignancy. Great care must be taken to make differential diagnosis with fibrosarcomas and malignant schwannoma. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

A phase I clinical trial evaluating imatinib mesylate (Gleevec) in tumor-bearing cats.

PubMed

Lachowicz, Joshua L; Post, Gerald S; Brodsky, Edwin

2005-01-01

A phase I clinical trial evaluating the toxicity of orally-administered imatinib mesylate was performed in 9 tumor-bearing cats. Imatinib is a small molecule, tyrosine kinase inhibitor, which selectively blocks the function of overexpressed proteins associated with various malignancies. Cats included in the study had diagnoses of fibrosarcoma, squamous cell carcinoma, and mast cell tumor, and each cat was staged using CBC and serum biochemistry; urinalysis, thoracic radiographs, and abdominal ultrasonography were performed in some cats. Most cats were treated previously by surgery, radiation therapy, chemotherapy, or some combination of these treatments. None of the cats received any concurrent chemotherapy. Six cats were treated with imatinib mesylate at 1-2 mg/kg PO q24h. Dose escalations were made to 2, 4, and 10 mg/kg PO q24h in 5 cats. Two cats started therapy at 10 mg/kg PO q24h, and 1 cat started therapy at 15 mg/kg PO q24h; all 3 cats remained at these dosages. No signs of toxicity, as evaluated by CBC and serum biochemistry, were noted in 8 of the 9 cats, and minimal gastrointestinal toxicity was observed. Due to the low frequency of adverse effects, further evaluation of imatinib is ongoing at a dosage of 10 mg/kg PO q24h.

Differential diagnosis of pediatric tumors of the nasal cavity and paranasal sinuses: a 45-year multi-institutional review.

PubMed

Holsinger, F Christopher; Hafemeister, Adam C; Hicks, M John; Sulek, Marcelle; Huh, Winston W; Friedman, Ellen M

2010-11-01

We conducted a retrospective case-series review to identify the various diagnoses of neoplasms of the nasal cavity and paranasal sinuses in a pediatric population. Our study group was made up of 54 children-23 boys and 31 girls, aged 8 months to 16 years (mean: 9 yr). All patients had been diagnosed with a tumor of the nasal cavity or paranasal sinuses between Jan. 1, 1955, and Dec. 31, 1999, at one of four university-based, tertiary care referral centers. We compiled data on tumoral characteristics (location, size, and histopathology), morbidity and mortality, and rates of recurrence. Lesions included adnexal neoplasm, ameloblastic fibro-odontoma, basal cell carcinoma, benign fibrous histiocytoma, blue nevus, chondrosarcoma, compound nevus, epithelioma adenoides cysticum, esthesioneuroblastoma, Ewing sarcoma, fibrosarcoma, giant cell granuloma, granulocytic sarcoma, hemangioma, hemangiopericytoma, Langerhans cell histiocytosis, lymphangioma, lymphoma, melanoma, neuroblastoma, neurofibroma, ossifying osteofibroma, osteochondroma, osteosarcoma, port wine stain, rhabdomyosarcoma, Spitz nevus, and xanthogranuloma. To the best of our knowledge, this is the largest such study of its kind to date. We believe that the large size of this study and the data on disease incidence will allow clinicians to be better informed of the differential diagnosis of neoplasms of the nasal cavity and paranasal sinuses in the pediatric population.

Endoscopic transnasal management of sinonasal malignancies – our initial experience

PubMed Central

Osuch-Wójcikiewicz, Ewa; Held-Ziółkowska, Marta; Kużmińska, Magdalena; Niemczyk, Kazimierz

2014-01-01

Introduction Malignant tumors of the paranasal sinuses are traditionally managed through external approaches. Advances in endoscopic transnasal surgery have allowed for the endoscopic treatment of some of these tumors. Aim To present the results of treatment of a series of patients with paranasal sinus malignancies treated with an endoscopic approach at a single institution. Material and methods The data on tumor type, operative technique, perioperative complications and postoperative course were analyzed. Results Eleven patients meeting the inclusion criteria were identified. The histopathology was as follows: malignant melanoma in 3 patients, squamous cell carcinoma in 2, adenocarcinoma in 2, poorly differentiated carcinoma in 1, hemangiopericytoma in 1, adenoid cystic carcinoma in 1 and fibrosarcoma in 1. There were no severe perioperative complications with the exception of 1 case of cerebrospinal fluid leak, which was successfully closed. The mean observation period was 13.5 months. One of the patients died of disease, another was lost to follow-up, and one was reoperated on due to recurrence. The remaining 8 patients are alive with no signs of recurrence. Conclusions Our initial experience seems to confirm results obtained by other authors indicating that in selected cases endoscopic surgery of sinonasal malignancies is similarly effective as external approach surgery. PMID:25097677

DOE Office of Scientific and Technical Information (OSTI.GOV)

Becerikli, Mustafa; Jacobsen, Frank; Rittig, Andrea

Soft tissue sarcomas (STS) are characterized by co-participation of several epigenetic and genetic events during tumorigenesis. Having bypassed cellular senescence barriers during oncogenic transformation, the factors further affecting growth rate of STS cells remain poorly understood. Therefore, we investigated the role of gene silencing (DNA promoter methylation of LINE-1, PTEN), genetic aberrations (karyotype, KRAS and BRAF mutations) as well as their contribution to the proliferation rate and migratory potential that underlies “initial” and “final” passage sarcoma cells. Three different cell lines were used, SW982 (synovial sarcoma), U2197 (malignant fibrous histiocytoma (MFH)) and HT1080 (fibrosarcoma). Increased proliferative potential of final passagemore » STS cells was not associated with significant differences in methylation (LINE-1, PTEN) and mutation status (KRAS, BRAF), but it was dependent on the amount of chromosomal aberrations. Collectively, our data demonstrate that these fairly differentiated/advanced cancer cell lines have still the potential to gain an additional spontaneous growth benefit without external influences and that maintenance of increased proliferative potential towards longevity of STS cells (having crossed senescence barriers) may be independent of overt epigenetic alterations. -- Highlights: Increased proliferative potential of late passage STS cells was: • Not associated with epigenetic changes (methylation changes at LINE-1, PTEN). • Not associated with mutation status of KRAS, BRAF. • Dependent on presence/absence of chromosomal aberrations.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chi, Hoang Thanh, E-mail: kk086406@mgs.k.u-tokyo.ac.jp; Ly, Bui Thi Kim; Kano, Yasuhiko

Highlights: Black-Right-Pointing-Pointer ETV6-NTRK3 is an oncogene with transformation activity in multiple cell lineages. Black-Right-Pointing-Pointer PKC412 could block ETV6-NTRK3 activation. Black-Right-Pointing-Pointer Loss of ETV6-NTRK3 phosphorylation leads to inactivation of its downstream signaling pathway. Black-Right-Pointing-Pointer Inhibition of ETV6-NTRK3 activation by PKC412 could be a novel strategy for the treatment. -- Abstract: The ETV6-NTRK3 (EN) fusion gene which encodes a chimeric tyrosine kinase was first identified by cloning of the t(12;15)(p13;q25) translocation in congenital fibrosarcoma (CFS). Since then, EN has been also found in congenital mesoblastic nephroma (CMN), secretory breast carcinoma (SBC) and acute myelogenous leukemia (AML). Using IMS-M2 and M0-91 cell linesmore » harboring the EN fusion gene, and Ba/F3 cells stably transfected with EN, we demonstrated that PKC412, also known as midostaurin, is an inhibitor of EN. Inhibition of EN activity by PKC412 suppressed the activity of it downstream molecules leading to inhibition of cell proliferation and induction of apoptosis. Our data for the first time suggested that PKC412 could serve as therapeutic drug for treatment of patients with this fusion.« less

Macroscopic singlet oxygen modeling for dosimetry of Photofrin-mediated photodynamic therapy: an in-vivo study

NASA Astrophysics Data System (ADS)

Qiu, Haixia; Kim, Michele M.; Penjweini, Rozhin; Zhu, Timothy C.

2016-08-01

Although photodynamic therapy (PDT) is an established modality for cancer treatment, current dosimetric quantities, such as light fluence and PDT dose, do not account for the differences in PDT oxygen consumption for different fluence rates (φ). A macroscopic model was adopted to evaluate using calculated reacted singlet oxygen concentration ([) to predict Photofrin-PDT outcome in mice bearing radiation-induced fibrosarcoma tumors, as singlet oxygen is the primary cytotoxic species responsible for cell death in type II PDT. Using a combination of fluences (50, 135, 200, and 250 J/cm2) and φ (50, 75, and 150 mW/cm2), tumor regrowth rate, k, was determined for each condition. A tumor cure index, CI=1-k/k, was calculated based on the k between PDT-treated groups and that of the control, k. The measured Photofrin concentration and light dose for each mouse were used to calculate PDT dose and [, while mean optical properties (μa=0.9 cm-1, μs‧=8.4 cm-1) were used to calculate φ for all mice. CI was correlated to the fluence, PDT dose, and [ with R2=0.35, 0.79, and 0.93, respectively. These results suggest that [ serves as a better dosimetric quantity for predicting PDT outcome.

Detection of EWS/FLI-1 fusion in non-Ewing soft tissue tumors.

PubMed

Trancău, I O; Huică, R; Surcel, M; Munteanu, A; Ursaciuc, C

2015-01-01

EWS/FLI-1 fusion mainly appears in Ewing's sarcoma or the primitive neuroectodermal tumors and represents a genomic marker for these tumors. However, it can appear with lower frequency in other soft tissue tumors. The paper investigates the presence of EWS/FLI-1 fusion in clinically diagnosed sarcoma belonging to different non-Ewing connective tissue tumors in order to search for a possible new biomarker valuable for investigators. 20 patients with soft tissue tumors, who underwent surgery, were tested. Intra-operative samples of normal and tumor tissue were collected for histopathological diagnosis and genetics determinations. The patients' RNA from tumor and normal peritumoral tissue was extracted and EWS/FLI-1 fusion screened by quantitative real-time PCR. The relative expression of the fusion in the tumor sample was compared to the similar expression in normal tissue. The amplification in the threshold zone was shown by 5 samples (25%): 2 clear cell sarcoma, 1 fibrosarcoma, 1 malignant tumor of nerve sheath, 1 metastatic adenocarcinoma. We differentiated between the unspecific amplification and concluded that these are weak positive results. Genomic investigation may establish the tumor malignancy and its possible affiliation earlier than histopathology. It can support the screening of EWS/FLI-1 fusion in a larger variety of clinically diagnosed soft tissue tumors.

In Vivo Demonstration of Cancer Molecular Imaging with Ultrasound Radiation Force and Buried-Ligand Microbubbles

PubMed Central

Borden, Mark A.; Streeter, Jason E.; Sirsi, Shashank R.; Dayton, Paul A.

2015-01-01

In designing targeted contrast agent materials for imaging, the need to present a targeting ligand for recognition and binding by the target is counterbalanced by the need to minimize interactions with plasma components and to avoid recognition by the immune system. We have previously reported on a microbubble imaging probe for ultrasound molecular imaging that uses a buried-ligand surface architecture to minimize unwanted interactions and immunogenicity. Here we examine for the first time the utility of this approach for in vivo molecular imaging. In accordance with previous results, we showed a threefold increase in circulation persistence through the tumor of a fibrosarcoma model in comparison with controls. The buried-ligand microbubbles were then activated for targeted adhesion through the application of noninvasive ultrasound radiation forces applied specifically to the tumor region. Using a clinical ultrasound scanner, microbubbles were activated, imaged, and silenced. The results showed visually conspicuous images of tumor neovasculature and a twofold increase in ultrasound radiation force enhancement of acoustic contrast intensity for buried-ligand microbubbles, whereas no such increase was found for exposed-ligand microbubbles. We therefore conclude that the use of acoustically active buried-ligand microbubbles for ultrasound molecular imaging bridges the demand for low immunogenicity with the necessity of maintaining targeting efficacy and imaging conspicuity in vivo. PMID:23981781

Involvement of CTGF, a hypertrophic chondrocyte-specific gene product, in tumor angiogenesis.

PubMed

Shimo, T; Nakanishi, T; Nishida, T; Asano, M; Sasaki, A; Kanyama, M; Kuboki, T; Matsumura, T; Takigawa, M

2001-01-01

Connective tissue growth factor (CTGF) is a potent secreted signaling factor which functions in multiple stages of angiogenesis. In the present study, we examined the role of CTGF in tumor angiogenesis and made the following observations: (1) Histological analysis of human breast cancer (MDA231) cell and human fibrosarcoma (HT1080) cell xenografts in BALB/c nude mice showed a high level of neovascularization. Human squamous cell carcinoma (A431) xenografts induced only a low level of neovascularization. (2) CTGF mRNA was strongly expressed in MDA231 and in HT1080 cells in vivo and in vitro, but not in A431 cells. (3) CTGF protein was markedly produced in MDA231 cells and HT1080 cells and secreted into culture medium, and its production was greater during phases of growth rather than confluency. (4) Production of CTGF in bovine aorta endothelial cells was induced by CTGF, VEGF, bFGF and TGF-beta. (5) Neovascularization induced by HT1080 cells or MDA231 cells on chicken chorioallantoic membrane was suppressed in the presence of neutralizing CTGF-specific polyclonal antibody. These results suggest that CTGF regulates progression in tumor angiogenesis and the release or secretion of CTGF from tumor cells is essential for the angiogenesis. Copyright 2001 S. Karger AG, Basel

Grafting of [(64)Cu]-TPPF20 porphyrin complex on Functionalized nano-porous MCM-41 silica as a potential cancer imaging agent.

PubMed

Fazaeli, Yousef; Feizi, Shahzad; Jalilian, Amir R; Hejrani, Ali

2016-06-01

Mesoporous silica, MCM-41, functionalized with 3-aminopropyltriethoxysilane (APTES) was investigated as a potential drug delivery system, using [(64)Cu]-5, 10, 15, 20-tetrakis penta fluorophenyl porphyrin complex. [(64)Cu]-TPPF20 complex was grafted on functionalized MCM-41. The product was characterized by paper chromatography, FTIR spectroscopy, low angle X-ray diffraction, CHN and TGA/DTA analyses and atomic force microscopy. The biological evaluations of the grafted complex, [(64)Cu]-TPPF20@NH2-MCM-41, were done in Fibrosarcoma tumor-bearing Sprague-Dawley rats using scarification studies and Sopha DST-XL Dual-Head SPECT system. The actual loading amount of aminopropyl groups was found about 1.6mmol per gram of final silica. The specific activity of the final compound was found to be 3Ci/g. Amine functionalized MCM-41 was found to be a good platform for theranostic radiopharmaceuticals such as copper-64 complexes. Considering the accumulation of the tracer in tumor cells, fast wash-out from normal tissues, the short half-life copper-64 and less imposed radiation doses to patients, [(64)Cu]-TPPF20@NH2-MCM-41 can potentially be a suitable candidate for tumor imaging applications and future PET studies. Copyright © 2016 Elsevier Ltd. All rights reserved.

MUC4 is a sensitive and extremely useful marker for sclerosing epithelioid fibrosarcoma: association with FUS gene rearrangement.

PubMed

Doyle, Leona A; Wang, Wei-Lien; Dal Cin, Paola; Lopez-Terrada, Dolores; Mertens, Fredrik; Lazar, Alexander J F; Fletcher, Christopher D M; Hornick, Jason L

2012-10-01

Sclerosing epithelioid fibrosarcoma (SEF) is a rare aggressive fibroblastic neoplasm composed of cords of epithelioid cells embedded in a dense collagenous stroma. The reported immunophenotype of SEF is nonspecific. Some SEF cases show morphologic and molecular overlap with low-grade fibromyxoid sarcoma (LGFMS), suggesting a relationship between these tumor types. MUC4 has recently been identified as a sensitive and specific marker for LGFMS; MUC4 expression was also observed in 2 tumors with hybrid features of SEF and LGFMS. We investigated MUC4 expression in SEF and other epithelioid soft tissue tumors to determine (1) the potential diagnostic utility of MUC4 for SEF and (2) the association between MUC4 expression and FUS rearrangement in SEF. Whole sections of 180 tumors were evaluated: 41 cases of SEF (including 29 "pure" SEF and 12 hybrid LGFMS-SEF), 20 epithelioid sarcomas, 11 clear cell sarcomas, 11 metastatic melanomas, 10 perivascular epithelioid cell tumors, 10 alveolar soft part sarcomas, 10 epithelioid angiosarcomas, 10 epithelioid hemangioendotheliomas, 10 epithelioid gastrointestinal stromal tumors, 10 myoepithelial carcinomas, 17 ossifying fibromyxoid tumors, 10 leiomyosarcomas, and 10 biphasic synovial sarcomas. Immunohistochemical analysis was performed after antigen retrieval using a mouse anti-MUC4 monoclonal antibody. Fluorescence in situ hybridization (FISH) was performed on 33 SEF cases using FUS break-apart probes. A subset of cases was also evaluated for EWSR1 and CREB3L2/L1 rearrangements by FISH. Strong diffuse cytoplasmic staining for MUC4 was observed in 32 of 41 (78%) cases of SEF, including all 12 hybrid tumors. FUS rearrangement was detected in 8 of 21 (38%) MUC4-positive cases of SEF with successful FISH studies. The prevalence of FUS rearrangement was similar in hybrid LGFMS-SEF (2 of 6; 33%) and SEF without an LGFMS component (6 of 15; 40%). FUS rearrangement was not detected in any cases of MUC4-negative SEF. Two hybrid tumors had both EWSR1 and CREB3L1 rearrangements. MUC4 expression was also seen in 9 of 10 (90%) biphasic synovial sarcomas, predominantly in the glandular component. All other tumor types were negative for MUC4, apart from focal reactivity in 5 ossifying fibromyxoid tumors, 2 epithelioid gastrointestinal stromal tumors, and 1 myoepithelial carcinoma. MUC4 is a sensitive and relatively specific marker for SEF among epithelioid soft tissue tumors. MUC4 expression occurs more frequently than FUS rearrangement in SEF. The finding of EWSR1 and CREB3L1 rearrangements in 2 cases of hybrid LGFMS-SEF suggests that SEFs are genetically heterogenous. MUC4-positive SEFs with FUS rearrangement are likely closely related to LGFMS. MUC4-positive SEFs that lack FUS rearrangement may be related to LGFMS but could have alternate fusion partners, including EWSR1. SEF without MUC4 expression may represent a distinct group of tumors. MUC4 expression correlates with glandular epithelial differentiation in biphasic synovial sarcoma and is very limited in other epithelioid soft tissue tumors.

Radionuclide injury to the lung.

PubMed Central

Dagle, G E; Sanders, C L

1984-01-01

Radionuclide injury to the lung has been studied in rats, hamsters, dogs, mice and baboons. Exposure of the lung to high dose levels of radionuclides produces a spectrum of progressively more severe functional and morphological changes, ranging from radiation pneumonitis and fibrosis to lung tumors. These changes are somewhat similar for different species. Their severity can be related to the absorbed radiation dose (measured in rads) produced by alpha, beta or gamma radiation emanating from various deposited radionuclides. The chemicophysical forms of radionuclides and spatial-temporal factors are also important variables. As with other forms of injury to the lung, repair attempts are highlighted by fibrosis and proliferation of pulmonary epithelium. Lung tumors are the principal late effect observed in experimental animals following pulmonary deposition of radionuclides at dose levels that do not result in early deaths from radiation pneumonitis or fibrosis. The predominant lung tumors described have been of epithelial origin and have been classified, in decreasing frequency of occurrence, as adenocarcinoma, bronchioloalveolar carcinoma, epidermoid carcinomas and combined epidermoid and adenocarcinoma. Mesothelioma and fibrosarcoma have been observed in rats, but less commonly in other species. Hemangiosarcomas were frequency observed in dogs exposed to beta-gamma emitters, and occasionally in rats exposed to alpha emitters. These morphologic changes in the lungs of experimental animals were reviewed and issues relevant to the prediction of human hazards discussed. PMID:6376095

A DTI Study to Probe Tumor Microstructure And Its Connection With Hypoxia

PubMed Central

Majumdar, Shreyan; Triplett, William; Epel, Boris; Halpern, Howard

2015-01-01

Solid tumors have chaotic organization of blood vessels, disruptive nerve paths and muscle fibers that result in a hostile and heterogeneous microenvironment. These tumor regions are often hypoxic and resistant to radiation therapy. The knowledge of partial pressure of oxygen concentration (pO2), in conjunction with the information about tissue organization, can predict tissue health and may eventually be used in combination with intensity-modulated radiation therapy (IMRT) for targeted destruction of radiation-resistant areas, while sparing healthy tissues. Diffusion tensor imaging (DTI) based parameter fractional anisotropy (FA) can be used to assess organization of tissue microstructure, whereas the pO2 can be measured using electron paramagnetic resonance oxygen imaging (EPROI). This study is our first step to connect these two important physiological parameters. We calculated FA in fixed fibrosarcoma (FSa) grown in hind leg of nude mice (n = 6) using preclinical 9.4 T MRI. The FA in tumor region (0.34 ± 0.014) was found to be lower when compared to normal surrounding region (0.36 ± 0.013). We hypothesized that the change in FA is directly correlated with the change in oxygen concentration in tumor. We present preliminary in vivo results showing a positive correlation (R = 0.85, p = 0.017) between the FA and pO2 values acquired for MCa4 tumor (n = 1) using DTI and EPROI. PMID:25570064

A DTI study to probe tumor microstructure and its connection with hypoxia.

PubMed

Majumdar, Shreyan; Kotecha, Mrignayani; Triplett, William; Epel, Boris; Halpern, Howard

2014-01-01

Solid tumors have chaotic organization of blood vessels, disruptive nerve paths and muscle fibers that result in a hostile and heterogeneous microenvironment. These tumor regions are often hypoxic and resistant to radiation therapy. The knowledge of partial pressure of oxygen concentration (pO2), in conjunction with the information about tissue organization, can predict tissue health and may eventually be used in combination with intensity-modulated radiation therapy (IMRT) for targeted destruction of radiation-resistant areas, while sparing healthy tissues. Diffusion tensor imaging (DTI) based parameter fractional anisotropy (FA) can be used to assess organization of tissue microstructure, whereas the pO2 can be measured using electron paramagnetic resonance oxygen imaging (EPROI). This study is our first step to connect these two important physiological parameters. We calculated FA in fixed fibrosarcoma (FSa) grown in hind leg of nude mice (n = 6) using preclinical 9.4 T MRI. The FA in tumor region (0.34 ± 0.014) was found to be lower when compared to normal surrounding region (0.36 ± 0.013). We hypothesized that the change in FA is directly correlated with the change in oxygen concentration in tumor. We present preliminary in vivo results showing a positive correlation (R = 0.85, p = 0.017) between the FA and pO2 values acquired for MCa4 tumor (n = 1) using DTI and EPROI.

Aluminum ammonium sulfate dodecahydrate purified from traditional Chinese medicinal herb Korean monkshood root is a potent matrix metalloproteinase inhibitor.

PubMed

Shen, Yehua; Liu, Sen; Jin, Fenghai; Mu, Tianyang; Li, Cong; Jiang, Kun; Tian, Weihua; Yu, Dahai; Zhang, Yingqi; Fang, Xuexun

2012-06-01

Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases and key regulators for many physiological and pathological functions. The MMP inhibitors have been shown to modulate diseases such as cancer, inflammation, and cardiovascular diseases. In this paper we tracked the MMP inhibitory activities of the traditional Chinese medicinal herb Korean Monkshood Root. The purified active ingredient was identified by the elemental analysis, infrared spectrum (IR) and X-ray diffraction as aluminum ammonium sulfate dodecahydrate. This inorganic compound showed inhibitory activities toward a number of MMP family members. In particular, it has a strong inhibitory effect toward MMP-2 and MMP-9, with IC50 values of 0.54 and 0.50 μM, respectively. Further analysis suggested that the MMP inhibitory activity is mainly due to Al(3+). Cell viability assays using human fibrosarcoma HT1080 cells showed aluminum ammonium sulfate had minimal cyto-toxicity with a concentration up to 500 μM. However, within 50 μM, it exhibited significant inhibition of cell invasion. To our knowledge, there has been no previous report of inorganic form of the MMP inhibitor with strong inhibitory activity. Our results for the first time showed that aluminum ammonium sulfate is an inorganic form of MMP inhibitor with high potency, and can be used to interfere with MMP related cellular processes.

Sequential processing of quantitative phase images for the study of cell behaviour in real-time digital holographic microscopy.

PubMed

Zikmund, T; Kvasnica, L; Týč, M; Křížová, A; Colláková, J; Chmelík, R

2014-11-01

Transmitted light holographic microscopy is particularly used for quantitative phase imaging of transparent microscopic objects such as living cells. The study of the cell is based on extraction of the dynamic data on cell behaviour from the time-lapse sequence of the phase images. However, the phase images are affected by the phase aberrations that make the analysis particularly difficult. This is because the phase deformation is prone to change during long-term experiments. Here, we present a novel algorithm for sequential processing of living cells phase images in a time-lapse sequence. The algorithm compensates for the deformation of a phase image using weighted least-squares surface fitting. Moreover, it identifies and segments the individual cells in the phase image. All these procedures are performed automatically and applied immediately after obtaining every single phase image. This property of the algorithm is important for real-time cell quantitative phase imaging and instantaneous control of the course of the experiment by playback of the recorded sequence up to actual time. Such operator's intervention is a forerunner of process automation derived from image analysis. The efficiency of the propounded algorithm is demonstrated on images of rat fibrosarcoma cells using an off-axis holographic microscope. © 2014 The Authors Journal of Microscopy © 2014 Royal Microscopical Society.

Extracellular matrix stiffness causes systematic variations in proliferation and chemosensitivity in myeloid leukemias.

PubMed

Shin, Jae-Won; Mooney, David J

2016-10-25

Extracellular matrix stiffness influences biological functions of some tumors. However, it remains unclear how cancer subtypes with different oncogenic mutations respond to matrix stiffness. In addition, the relevance of matrix stiffness to in vivo tumor growth kinetics and drug efficacy remains elusive. Here, we designed 3D hydrogels with physical parameters relevant to hematopoietic tissues and adapted them to a quantitative high-throughput screening format to facilitate mechanistic investigations into the role of matrix stiffness on myeloid leukemias. Matrix stiffness regulates proliferation of some acute myeloid leukemia types, including MLL-AF9 + MOLM-14 cells, in a biphasic manner by autocrine regulation, whereas it decreases that of chronic myeloid leukemia BCR-ABL + K-562 cells. Although Arg-Gly-Asp (RGD) integrin ligand and matrix softening confer resistance to a number of drugs, cells become sensitive to drugs against protein kinase B (PKB or AKT) and rapidly accelerated fibrosarcoma (RAF) proteins regardless of matrix stiffness when MLL-AF9 and BCR-ABL are overexpressed in K-562 and MOLM-14 cells, respectively. By adapting the same hydrogels to a xenograft model of extramedullary leukemias, we confirm the pathological relevance of matrix stiffness in growth kinetics and drug sensitivity against standard chemotherapy in vivo. The results thus demonstrate the importance of incorporating 3D mechanical cues into screening for anticancer drugs.

In vivo EPR imaging of differential tumor targeting using cis-3,4-di(acetoxymethoxycarbonyl)-2,2,5,5-tetramethyl-1-pyrrolidinyloxyl

PubMed Central

Redler, Gage; Barth, Eugene D.; Bauer, Kenneth S.; Kao, Joseph P.Y.; Rosen, Gerald M.; Halpern, Howard J.

2015-01-01

Purpose EPR spectroscopy promises quantitative images of important physiologic markers of animal tumors and normal tissues, such as pO2, pH, and thiol redox status. These parameters of tissue function are conveniently reported by tailored nitroxides. For defining tumor physiology, it is vital that nitroxides are selectively localized in tumors relative to normal tissue. Furthermore, these paramagnetic species should be specifically taken up by cells of the tumor, thereby reporting on both the site of tumor formation and the physiological status of the tissue. This study investigates the tumor localization of the novel nitroxide, cis-3,4-di(acetoxymethoxycarbonyl)-2,2,5,5-tetramethyl-1-pyrrolidinyloxyl 3 relative to the corresponding di-acid 4. Methods We obtained images of nitroxide 3 infused intravenously into C3H mice bearing 0.5-cm3 FSa fibrosarcoma on the leg, and compared these with images of similar tumors infused with nitroxide 4. Results The ratio of spectral intensity from within the tumor-bearing region to that of normal tissue was higher in the mice injected with 3 relative to 4. Conclusion This establishes the possibility of tumor imaging with a nitroxide with intracellular distribution and provides the basis for EPR images of animal models to investigate the relationship between crucial aspects of tumor microenvironment and malignancy and its response to therapy. PMID:23776127

Identification of a novel missense mutation of MAF in a Japanese family with congenital cataract by whole exome sequencing: a clinical report and review of literature.

PubMed

Narumi, Yoko; Nishina, Sachiko; Tokimitsu, Motoharu; Aoki, Yoko; Kosaki, Rika; Wakui, Keiko; Azuma, Noriyuki; Murata, Toshinori; Takada, Fumio; Fukushima, Yoshimitsu; Kosho, Tomoki

2014-05-01

Congenital cataracts are the most important cause of severe visual impairment in infants. Genetic factors contribute to the disease development and 29 genes are known to cause congenital cataracts. Identifying the genetic cause of congenital cataracts can be difficult because of genetic heterogeneity. V-maf avian musculoaponeurotic fibrosarcoma oncogene homolog (MAF) encodes a basic region/leucine zipper transcription factor that plays a key role as a regulator of embryonic lens fiber cell development. MAF mutations have been reported to cause juvenile-onset pulverulent cataract, microcornea, iris coloboma, and other anterior segment dysgenesis. We report on six patients in a family who have congenital cataracts were identified MAF mutation by whole exome sequencing (WES). The heterozygous MAF mutation Q303L detected in the present family occurs in a well conserved glutamine residue at the basic region of the DNA-binding domain. All affected members showed congenital cataracts. Three of the six members showed microcornea and one showed iris coloboma. Congenital cataracts with MAF mutation exhibited phenotypically variable cataracts within the family. Review of the patients with MAF mutations supports the notion that congenital cataracts caused by MAF mutations could be accompanied by microcornea and/or iris coloboma. WES is a useful tool for detecting disease-causing mutations in patients with genetically heterogeneous conditions. © 2014 Wiley Periodicals, Inc.

Cell-penetrating peptide-doxorubicin conjugate loaded NGR-modified nanobubbles for ultrasound triggered drug delivery.

PubMed

Lin, Wen; Xie, Xiangyang; Deng, Jianping; Liu, Hui; Chen, Ying; Fu, Xudong; Liu, Hong; Yang, Yang

2016-01-01

A new drug-targeting system for CD13(+) tumors has been developed, based on ultrasound-sensitive nanobubbles (NBs) and cell-permeable peptides (CPPs). Here, the CPP-doxorubicin conjugate (CPP-DOX) was entrapped in the asparagine-glycine-arginine (NGR) peptide modified NB (CPP-DOX/NGR-NB) and the penetration of CPP-DOX was temporally masked; local ultrasound stimulation could trigger the CPP-DOX release from NB and activate its penetration. The CPP-DOX/NGR-NBs had particle sizes of about 200 nm and drug entrapment efficiency larger than 90%. In vitro release results showed that over 85% of the encapsulated DOX or CPP-DOX would release from NBs in the presence of ultrasound, while less than 1.5% of that (30 min) without ultrasound. Cell experiments showed the higher cellular CPP-DOX uptake of CPP-DOX/NGR-NB among the various NB formulations in Human fibrosarcoma cells (HT-1080, CD13(+)). The CPP-DOX/NGR-NB with ultrasound treatment exhibited an increased cytotoxic activity than the one without ultrasound. In nude mice xenograft of HT-1080 cells, CPP-DOX/NGR-NB with ultrasound showed a higher tumor inhibition effect (3.1% of T/C%, day 24), longer median survival time (50 days) and excellent body safety compared with the normal DOX injection group. These results indicate that the constructed vesicle would be a promising drug delivery system for specific cancer treatment.

AP-1 mediated transcriptional repression of matrix metalloproteinase-9 by recruitment of histone deacetylase 1 in response to interferon β.

PubMed

Mittelstadt, Megan L; Patel, Rekha C

2012-01-01

Matrix metalloproteinase-9 (MMP-9) is a 92 kDa zinc-dependant endopeptidase that degrades components of the extracellular matrix. Increased expression of MMP-9 is implicated in many pathological conditions including metastatic cancer, multiple sclerosis, and atherosclerosis. Although it has been widely noted that interferon-β (IFNβ) downregulates both the basal and phorbol 12-myristate 13-acetate (PMA)-induced MMP-9 expression at the transcriptional level, the molecular mechanism of this repression is poorly understood. In the present study we identify a novel mechanism for repression of MMP-9 transcription by IFNβ in HT1080 fibrosarcoma cells. Using reporter assays with promoter deletion constructs we show that IFNβ's inhibitory effects require a region of the promoter between -154 and -72, which contains an AP-1 binding site. Chromatin immunoprecipitation (ChIP) studies indicate that IFNβ increases histone deacetylase (HDAC)-1 recruitment to the MMP-9 promoter and reduces histone H3 acetylation, in addition to reduced NF-κB recruitment. ChIP analysis shows that IFNβ induced HDAC1 recruitment to the MMP-9 promoter and IFNβ mediated transcriptional repression is lost when the AP-1 binding site is inactivated by a point mutation. Altogether, our results establish that the repression of MMP-9 transcription in response to IFNβ occurs by the recruitment of HDAC1 via the proximal AP-1 binding site.

Quantitation of Cellular Metabolic Fluxes of Methionine

PubMed Central

Shlomi, Tomer; Fan, Jing; Tang, Baiqing; Kruger, Warren D.; Rabinowitz, Joshua D.

2014-01-01

Methionine is an essential proteogenic amino acid. In addition, it is a methyl donor for DNA and protein methylation and a propylamine donor for polyamine biosyn-thesis. Both the methyl and propylamine donation pathways involve metabolic cycles, and methods are needed to quantitate these cycles. Here, we describe an analytical approach for quantifying methionine metabolic fluxes that accounts for the mixing of intracellular and extracellular methionine pools. We observe that such mixing prevents isotope tracing experiments from reaching the steady state due to the large size of the media pools and hence precludes the use of standard stationary metabolic flux analysis. Our approach is based on feeding cells with 13C methionine and measuring the isotope-labeling kinetics of both intracellular and extracellular methionine by liquid chromatography−mass spectrometry (LC-MS). We apply this method to quantify methionine metabolism in a human fibrosarcoma cell line and study how methionine salvage pathway enzyme methylthioadenosine phosphorylase (MTAP), frequently deleted in cancer, affects methionine metabolism. We find that both transmethylation and propylamine transfer fluxes amount to roughly 15% of the net methionine uptake, with no major changes due to MTAP deletion. Our method further enables the quantification of flux through the pro-tumorigenic enzyme ornithine decarboxylase, and this flux increases 2-fold following MTAP deletion. The analytical approach used to quantify methionine metabolic fluxes is applicable for other metabolic systems affected by mixing of intracellular and extracellular metabolite pools. PMID:24397525

On-command on/off switching of progenitor cell and cancer cell polarized motility and aligned morphology via a cytocompatible shape memory polymer scaffold.

PubMed

Wang, Jing; Quach, Andy; Brasch, Megan E; Turner, Christopher E; Henderson, James H

2017-09-01

In vitro biomaterial models have enabled advances in understanding the role of extracellular matrix (ECM) architecture in the control of cell motility and polarity. Most models are, however, static and cannot mimic dynamic aspects of in vivo ECM remodeling and function. To address this limitation, we present an electrospun shape memory polymer scaffold that can change fiber alignment on command under cytocompatible conditions. Cellular response was studied using the human fibrosarcoma cell line HT-1080 and the murine mesenchymal stem cell line C3H/10T1/2. The results demonstrate successful on-command on/off switching of cell polarized motility and alignment. Decrease in fiber alignment causes a change from polarized motility along the direction of fiber alignment to non-polarized motility and from aligned to unaligned morphology, while increase in fiber alignment causes a change from non-polarized to polarized motility along the direction of fiber alignment and from unaligned to aligned morphology. In addition, the findings are consistent with the hypothesis that increased fiber alignment causes increased cell velocity, while decreased fiber alignment causes decreased cell velocity. On-command on/off switching of cell polarized motility and alignment is anticipated to enable new study of directed cell motility in tumor metastasis, in cell homing, and in tissue engineering. Copyright © 2017 Elsevier Ltd. All rights reserved.

Explicit dosimetry for 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a-mediated photodynamic therapy: macroscopic singlet oxygen modeling.

PubMed

Penjweini, Rozhin; Liu, Baochang; Kim, Michele M; Zhu, Timothy C

2015-01-01

Type II photodynamic therapy (PDT) is based on the photochemical reactions mediated through an interaction between a photosensitizer, ground-state oxygen ([(3)O2]), and light excitation at an appropriate wavelength, which results in production of reactive singlet oxygen ([(1)O2]rx). We use an empirical macroscopic model based on four photochemical parameters for the calculation of [(1)O2]rx threshold concentration ([(1)O2]rx,sh) causing tissue necrosis in tumors after PDT. For this reason, 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a (HPPH)-mediated PDT was performed interstitially on mice with radiation-induced fibrosarcoma (RIF) tumors. A linear light source at 665 nm with total energy released per unit length of 12 to 100  J/cm and source power per unit length (LS) of 12 to 150  mW/cm was used to induce different radii of necrosis. Then the amount of [(1)O2]rx calculated by the macroscopic model incorporating explicit PDT dosimetry of light fluence distribution, tissue optical properties, and HPPH concentration was correlated to the necrotic radius to obtain the model parameters and [(1)O2]rx,sh. We provide evidence that [(1)O2]rx is a better dosimetric quantity for predicting the treatment outcome than PDT dose, which is proportional to the time integral of the products of the photosensitizer concentration and light fluence rate.

Explicit dosimetry for 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a-mediated photodynamic therapy: macroscopic singlet oxygen modeling

PubMed Central

Penjweini, Rozhin; Liu, Baochang; Kim, Michele M.; Zhu, Timothy C.

2015-01-01

Abstract. Type II photodynamic therapy (PDT) is based on the photochemical reactions mediated through an interaction between a photosensitizer, ground-state oxygen ([O32]), and light excitation at an appropriate wavelength, which results in production of reactive singlet oxygen ([O12]rx). We use an empirical macroscopic model based on four photochemical parameters for the calculation of [O12]rx threshold concentration ([O12]rx,sh) causing tissue necrosis in tumors after PDT. For this reason, 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a (HPPH)-mediated PDT was performed interstitially on mice with radiation-induced fibrosarcoma (RIF) tumors. A linear light source at 665 nm with total energy released per unit length of 12 to 100  J/cm and source power per unit length (LS) of 12 to 150  mW/cm was used to induce different radii of necrosis. Then the amount of [O12]rx calculated by the macroscopic model incorporating explicit PDT dosimetry of light fluence distribution, tissue optical properties, and HPPH concentration was correlated to the necrotic radius to obtain the model parameters and [O12]rx,sh. We provide evidence that [O12]rx is a better dosimetric quantity for predicting the treatment outcome than PDT dose, which is proportional to the time integral of the products of the photosensitizer concentration and light fluence rate. PMID:26720883

Explicit dosimetry for 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a-mediated photodynamic therapy: macroscopic singlet oxygen modeling

NASA Astrophysics Data System (ADS)

Penjweini, Rozhin; Liu, Baochang; Kim, Michele M.; Zhu, Timothy C.

2015-12-01

Type II photodynamic therapy (PDT) is based on the photochemical reactions mediated through an interaction between a photosensitizer, ground-state oxygen ([O]), and light excitation at an appropriate wavelength, which results in production of reactive singlet oxygen ([]rx). We use an empirical macroscopic model based on four photochemical parameters for the calculation of []rx threshold concentration ([]rx,sh) causing tissue necrosis in tumors after PDT. For this reason, 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a (HPPH)-mediated PDT was performed interstitially on mice with radiation-induced fibrosarcoma (RIF) tumors. A linear light source at 665 nm with total energy released per unit length of 12 to 100 J/cm and source power per unit length (LS) of 12 to 150 mW/cm was used to induce different radii of necrosis. Then the amount of []rx calculated by the macroscopic model incorporating explicit PDT dosimetry of light fluence distribution, tissue optical properties, and HPPH concentration was correlated to the necrotic radius to obtain the model parameters and []rx,sh. We provide evidence that []rx is a better dosimetric quantity for predicting the treatment outcome than PDT dose, which is proportional to the time integral of the products of the photosensitizer concentration and light fluence rate.

Single inhalation exposure to 90SrCl2 in the beagle dog: late biological effects.

PubMed

Gillett, N A; Muggenburg, B A; Boecker, B B; Griffith, W C; Hahn, F F; McClellan, R O

1987-08-01

Late-occurring biologic effects were studied in beagle dogs that were given graded levels of 90SrCl2 via single brief inhalation exposures and were subsequently observed for their life-span. Due to the soluble chemical form of the aerosol, 90Sr was rapidly translocated from lung and deposited in bone where it was subsequently retained for a long period of time. Radiation-induced lesions were confined to the bone, bone marrow, and adjacent soft tissue. Forty-five primary bone tumors occurred in 31 of 66 exposed dogs. Metastasis occurred from 21 tumors, with the lung being the most frequent site of metastasis (76%). Twenty-seven tumors were classified as different subtypes of osteosarcoma, 14 as hemangiosarcomas, 3 as fibrosarcomas, and 1 as a myxosarcoma. Four carcinomas arising from soft tissues adjacent to bone were also considered to be 90Sr induced. In contrast to bone tumors arising in beagles chronically exposed to 90Sr through ingestion, histologic lesions of radiation osteodystrophy were minimal in this study, indicating that these lesions are not a necessary precursor of osteosarcoma development. The incidences of hemangiosarcomas (31%) and telangiectatic osteosarcomas (11%) in addition to osteosarcomas suggest that the cell of origin for all of these neoplasms is a multipotent mesenchymal cell with the potential for various morphologic expressions dependent on local environmental factors.

Microwave-assisted one-pot synthesis of new phenanthrene fused-tetrahydrodibenzo-acridinones as potential cytotoxic and apoptosis inducing agents.

PubMed

Kumar, Niggula Praveen; Sharma, Pankaj; Reddy, T Srinivasa; Shankaraiah, Nagula; Bhargava, Suresh K; Kamal, Ahmed

2018-05-10

An expeditious microwave-assisted one-pot synthesis of new cytotoxic phenanthrene fused-tetrahydrodibenzo-acridinones has been successfully accomplished. This protocol offers wide substrate scope, catalyst-free synthesis, atom-economy, simple recrystallization, high yields, and ethanol was used as green solvent. These new compounds were tested for their in vitro cytotoxicity against cervical (HeLa), prostate (PC-3), fibrosarcoma (HT-1080), ovarian (SKOV-3) cancer cells, and were safer to normal (Hek-293T) kidney cell line. All the compounds have displayed significant cytotoxicity profile, among them 8m being the most potent compound with an IC 50 0.24 ± 0.05 μM against SKOV-3 ovarian cancer cells. Flow cytometry analysis revealed that cells were blocked at the G2/M phase of the cell cycle. The effect of 8m on F-actin polymerisation was also studied. Hoechst staining clearly showed the decreased number of viable cells and indicated apoptosis progression. Compound 8m caused the collapse of mitochondrial membrane potential as observed via JC-1 staining and also enhanced the generation of reactive oxygen species. The increase of caspase-3 activation by 3.7 folds supported the strong apoptosis induction. In addition, an in vitro 3D-spheroid progression assay was performed with 8m that significantly suppressed the tumor cells. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

[Cerebral gliosarcoma: clinico-pathologic study of 8 cases].

PubMed

Ayadi, Lobna; Charfi, Slim; Khabir, Abdemajid; Kalle, Rim; Sellami, Ahmed; Makni, Saloua; Boudawara, Zaher; Sellami-Boudawara, Tahya

2010-03-01

Gliosarcomas are biphasic neoplasms composed of a glioblastoma admixed to a sarcomatous component with different lines of differentiation. Histogenesis of these tumors is still discussed. Our objective is to specify clinical and pathological characteristics of this rare neoplasm and to discuss its histogenesis. Retrospective study of eight cases of gliosarcomas diagnosed between January 1998 and December 2004. Clinical, radiological, therapeutic and follow-up data were reviewed. Histological features and immunohistochemical results were also included in this review. Five patients were male, three women with a median age of 50.7 (range 31-74 years). Symptoms were dominated by intracranial hypertension and paralysis. The most common location was parietal or temporo-parietal (5 cases: 62.5%). Pathological exam including histochemical and immunohistochemical study confirmed the diagnosis of gliosarcoma in all cases. Sarcomatous component had features of fibrosarcoma in 5 cases, osteosarcoma in 2 cases and malignant fibrous histiocytoma in 1 case. All patients were treated by surgical excision (complete in five cases and partial in three cases). Adjuvant radiotherapy was received in three cases. One patient was lost on follow-up. Two patients died from postoperative. complications and the five remaining patients died with a medium follow up of 9 months (extremes: 2-24 months). Clinical, radiological and follow-up features of gliosarcomas share great similarities with glioblastomas. Histopathological, histochemical and immunohistochemical studies are helpful in accuracy diagnosis. Recent cytogenetic and molecular data support a monoclonal origin for these tumors.

A new gallium complex inhibits tumor cell invasion and matrix metalloproteinase MMP-14 expression and activity.

PubMed

Mohsen, Ahmed; Collery, Philippe; Garnotel, Roselyne; Brassart, Bertrand; Etique, Nicolas; Mohamed Sabry, Gilane; Elsherif Hassan, Rasha; Jeannesson, Pierre; Desmaële, Didier; Morjani, Hamid

2017-08-16

In this study, we investigated the effect of [N-(5-chloro-2-hydroxyphenyl)-l-aspartato] chlorogallate (GS2), a new water soluble gallium complex, on cell invasion and on the expression and activity of matrix metalloproteinases (MMPs) in human metastatic HT-1080 fibrosarcoma and MDA-MB 231 breast carcinoma cells. The effect on cell invasion was studied using a modified Boyden chamber coated with a type-I collagen. We analyzed the effect of GS2 on MMP-2, MMP-9, and MMP-14 via zymography and enzymatic assay using high affinity fluorogenic substrates. The expression of MMP mRNA was analyzed via qRT-PCR. GS2 induced a decrease in cell invasion. A dose-dependent inhibition effect was observed on the activities of MMP-2, MMP-9, and MMP-14 with the IC 50 values of 168, 82, and 20 μM, respectively. A decrease in the expression of MMP-14 mRNA was observed in both cell lines, whereas the expression of MMP-2 and MMP-9 mRNA was decreased only in the MDA-MB231 cells. Data obtained for the expression of MMP-14 mRNA were confirmed via Western blotting. In fact, MMP-14 expression was decreased in the presence of GS2. Overall, these data show that GS2 is a promising compound for anti-invasive and anticancer therapy.

Defective heat shock factor 1 inhibits the growth of fibrosarcoma derived from simian virus 40/T antigen-transformed MEF cells

PubMed Central

JIANG, QIYING; ZHANG, ZHI; LI, SHULIAN; WANG, ZHAOYANG; MA, YUANFANG; HU, YANZHONG

2015-01-01

Heat shock factor 1 (Hsf1) serves an important role in regulating the proliferation of human tumor cell lines in vitro and tissue specific tumorigenesis in certain mouse models. However, its role in viral-oncogenesis remains to be fully elucidated. In the current study, the role of Hsf1 in fibroblastoma derived from simian virus 40/T antigen (SV40/TAG)-transformed mouse embryonic fibroblast (MEF) cell lines was investigated. Knockout of Hsf1 inhibited MEF cell proliferation in vitro and fibroblastoma growth and metastasis to the lungs in vivo in nude mice. Knockout of Hsf1 increased the protein expression levels of p53 and phosphorylated retinoblastoma protein (pRb), however reduced the expression of heat shock protein 25 (Hsp25) in addition to the expression of the angiogenesis markers vascular endothelial growth factor, cluster of differentiation 34 and factor VIII related antigen. Furthermore, immunoprecipitation indicated that knockout of Hsf1 inhibited the association between SV40/TAG and p53 or pRb. These data suggest that Hsf1 is involved in the regulation of SV40/TAG-derived fibroblastoma growth and metastasis by modulating the association between SV40/TAG and tumor suppressor p53 and pRb. The current study provides further evidence that Hsf1 may be a novel therapeutic target in the treatment of cancer. PMID:26352782

Regulatory elements involved in constitutive and phorbol ester-inducible expression of the plasminogen activator inhibitor type 2 gene promoter.

PubMed Central

Cousin, E; Medcalf, R L; Bergonzelli, G E; Kruithof, E K

1991-01-01

Gene transcription rates and mRNA levels of plasminogen activator inhibitor type 2 (PAI-2) are markedly induced by the tumor promoting agent phorbol 12-myristate 13-acetate (PMA) in human HT1080 fibrosarcoma cells. To identify promoter elements required for basal-, and phorbol ester-inducible expression, deletion mutants of the PAI-1 promoter fused to the chloramphenicol acetyl transferase (CAT) reporter gene, were transiently expressed in HT1080 cells. Constitutive CAT activity was expressed from constructs containing more than 215 bp of promoter sequence, whereas deletion to position -91 bp abolished CAT gene expression. Treatment of transfected cells with PMA resulted in a three- to ten-fold increase in CAT expression from all constructs except from the construct shortened to position -91. DNAse1 protection analysis of the promoter region between -215 and the transcription initiation site revealed numerous protected regions, including two AP1-like binding sites (AP1a and AP1b) and one CRE-like element. Site-directed mutagenesis of the AP1a site or of the CRE-like site resulted in the loss of basal CAT activity and abolished the PMA effect, whereas mutagenesis of AP1b only partially inhibited basal and PMA-mediated expression. Our results suggest that the PAI-2 promoter contains at least two elements required for basal gene transcription and PMA-mediated induction. Images PMID:1650454

Nasofacial defect following fibrosarcoma excision and radiotherapy.

PubMed

Burget, G L; Panje, W R; Krause, C J

1988-01-01

For initial reconstruction, Dr. Burget suggests that he would have advanced the cheek flap medially toward the nasal septum and, subsequently, reconstructed the missing right half of the nose with a forehead flap and cartilage grafts. Dr. Panje suggested early prosthetic rehabilitation, while Dr. Krause's concepts were similar to Dr. Burget's, with forehead flap nasal reconstruction, after cheek reconstruction to the nasofacial and nasolabial lines with a medially advanced cheek flap. Dr. Panje recommended an immediate maxillary denture prosthesis, as did Dr. Krause (who supplemented this with foam rubber). Dr. Burget placed the prosthesis 3 weeks after tumor ablation. For skin grafts, Drs. Panje and Burget suggested split thickness grafts to all new surfaces to decrease wound contracture, while Dr. Krause used dermis grafts for the same purpose. Other reconstructive methods mentioned were the (1) cervical tubed flap, (2) free scapular flap, (3) Washio flap, (4) tissue expansion, and (5) nasolabial flap. Suggestions for isolated defects included: Lower eyelid--increase internal support by building up the prosthesis; release lower lid from deltopectoral flap and V-Y advancement; support graft or irradiated cartilage (1-2 mm sheet) under orbicularis oculi. Nasal ala--bring present ala down and insert cartilage graft; turn internal skin down and fill the resulting defect with a composite graft. Upper lip--multiple Z-plasty. Retrodisplacement of cheek due to maxillectomy--release buccal scar; skin graft the raw internal surface and build up prosthesis.

Sinonasal teratocarcinosarcoma: a clinical and pathological analysis.

PubMed

Yang, Shudong; Sun, Rongchao; Liang, Jiabei; Zhou, Zhiyi; Zhou, Jing; Rui, Jun

2013-02-01

The goal of this study was to assess the pathological and differential diagnoses of sinonasal teratocarcinosarcoma (SNTCS) in order to ultimately improve the diagnosis and treatment of this rare disease. Data from 2 cases of sinonasal teratocarcinosarcoma from the Wuxi People's Hospital (China) were analyzed. The clinical presentation for these patients consisted of nasal obstruction, epistaxis, and headache. On further physical examination, the presence of a polypoid mass was identified and, despite surgery and radiotherapy, both cases experienced recurrence. Histologically, the tumors showed a heterogeneous mixture of components from the 3 germ layers, primitive neuroepithelial elements, diagnostic immature squamous cell nests (clear cell nests), and various epithelial and mesenchymal components. Staining of the different germ layers corresponded with the appropriate immune markers. In case 1, the postradiotherapy resection specimen was completely dominated by a mature teratoma, with a complete absence of the corresponding adenocarcinoma and fibrosarcoma components. To date, this is the first study describing this composition within an SNTCS recurrent tumor. In summary, SNTCS is a rare tumor characterized by the presence of benign and malignant epithelial, mesenchymal, and dysembryomal components. Owing to its heterogeneous histologic appearance, adequate sampling and recognition of all SNTCS components are needed for future diagnosis. Currently, surgical removal, postoperative radiotherapy, and a histology-specific multidrug chemotherapy appear to be the best therapeutic approach. Future individualized therapy may also hold promise.

Efficacy of mitoxantrone against various neoplasms in dogs.

PubMed

Ogilvie, G K; Obradovich, J E; Elmslie, R E; Vail, D M; Moore, A S; Straw, R C; Dickinson, K; Cooper, M F; Withrow, S J

1991-05-01

One hundred twenty-six dogs with histologically confirmed, measurable malignant tumors were evaluated in a prospective study to determine the response to the antineoplastic drug mitoxantrone. Ninety-five dogs had been refractory to one or more treatment modalities (surgery, n = 57; chemotherapy other than mitoxantrone, n = 37; radiation, n = 4; whole body hyperthermia, n = 1). The extent of neoplastic disease was determined immediately before each dose of mitoxantrone was administered (1 to 10 doses, 2.5 to 5 mg/m2 of body surface area, IV) 21 days apart. Each dog was treated with mitoxantrone until the dog developed progressive disease or until the dog's quality of life diminished to an unacceptable level as determined by the owner or attending veterinarian. A partial or complete remission (greater than 50% volume reduction) was obtained in 23% (29/126) of all dogs treated. Tumors in which there was a partial or complete remission included lymphoma (11/32), squamous cell carcinoma (4/9), fibrosarcoma (2/9), thyroid carcinoma (1/10), transitional cell carcinoma (1/6), mammary adenocarcinoma (1/6), hepatocellular carcinoma (1/4), renal adenocarcinoma (1/1), rectal carcinoma (1/1), chondrosarcoma (1/2), oral malignant melanoma (1/12), cutaneous malignant melanoma (1/1), myxosarcoma (1/1), mesothelioma (1/1), and hemangiopericytoma (1/1). Our results indicated that mitoxantrone induces measurable regression in various malignant tumors in dogs.

Type I collagen aging impairs discoidin domain receptor 2-mediated tumor cell growth suppression

PubMed Central

Saby, Charles; Buache, Emilie; Brassart-Pasco, Sylvie; El Btaouri, Hassan; Courageot, Marie-Pierre; Van Gulick, Laurence; Garnotel, Roselyne; Jeannesson, Pierre; Morjani, Hamid

2016-01-01

Tumor cells are confronted to a type I collagen rich environment which regulates cell proliferation and invasion. Biological aging has been associated with structural changes of type I collagen. Here, we address the effect of collagen aging on cell proliferation in a three-dimensional context (3D). We provide evidence for an inhibitory effect of adult collagen, but not of the old one, on proliferation of human fibrosarcoma HT-1080 cells. This effect involves both the activation of the tyrosine kinase Discoidin Domain Receptor 2 (DDR2) and the tyrosine phosphatase SHP-2. DDR2 and SHP-2 were less activated in old collagen. DDR2 inhibition decreased SHP-2 phosphorylation in adult collagen and increased cell proliferation to a level similar to that observed in old collagen. In the presence of old collagen, a high level of JAK2 and ERK1/2 phosphorylation was observed while expression of the cell cycle negative regulator p21CIP1 was decreased. Inhibition of DDR2 kinase function also led to an increase in ERK1/2 phosphorylation and a decrease in p21CIP1 expression. Similar signaling profile was observed when DDR2 was inhibited in adult collagen. Altogether, these data suggest that biological collagen aging could increase tumor cell proliferation by reducingthe activation of the key matrix sensor DDR2. PMID:27121132

Ebselen treatment prevents islet apoptosis, maintains intranuclear Pdx-1 and MafA levels, and preserves β-cell mass and function in ZDF rats.

PubMed

Mahadevan, Jana; Parazzoli, Susan; Oseid, Elizabeth; Hertzel, Ann V; Bernlohr, David A; Vallerie, Sara N; Liu, Chang-qin; Lopez, Melissa; Harmon, Jamie S; Robertson, R Paul

2013-10-01

We reported earlier that β-cell-specific overexpression of glutathione peroxidase (GPx)-1 significantly ameliorated hyperglycemia in diabetic db/db mice and prevented glucotoxicity-induced deterioration of β-cell mass and function. We have now ascertained whether early treatment of Zucker diabetic fatty (ZDF) rats with ebselen, an oral GPx mimetic, will prevent β-cell deterioration. No other antihyperglycemic treatment was given. Ebselen ameliorated fasting hyperglycemia, sustained nonfasting insulin levels, lowered nonfasting glucose levels, and lowered HbA1c levels with no effects on body weight. Ebselen doubled β-cell mass, prevented apoptosis, prevented expression of oxidative stress markers, and enhanced intranuclear localization of pancreatic and duodenal homeobox (Pdx)-1 and v-maf musculoaponeurotic fibrosarcoma oncogene family, protein A (MafA), two critical insulin transcription factors. Minimal β-cell replication was observed in both groups. These findings indicate that prevention of oxidative stress is the mechanism whereby ebselen prevents apoptosis and preserves intranuclear Pdx-1 and MafA, which, in turn, is a likely explanation for the beneficial effects of ebselen on β-cell mass and function. Since ebselen is an oral antioxidant currently used in clinical trials, it is a novel therapeutic candidate to ameliorate fasting hyperglycemia and further deterioration of β-cell mass and function in humans undergoing the onset of type 2 diabetes.

Application of 23Na MRI to Monitor Chemotherapeutic Response in RIF-1 Tumors1

PubMed Central

Babsky, Andriy M; Hekmatyar, Shahryar K; Zhang, Hong; Solomon, James L; Bansal, Navin

2005-01-01

Abstract Effects of an alkylating anticancer drug, cyclophosphamide (Cp), on 23Na signal intensity (23Na SI) and water apparent diffusion coefficient (ADC) were examined in subcutaneously-implanted radiation-induced fibrosarcoma (RIF-1) tumors by in vivo 23Na and 1H magnetic resonance imaging (MRI). MRI experiments were performed on untreated control (n = 5) and Cp-treated (n = 6) C3H mice, once before Cp injection (300 mg/kg) then daily for 3 days after treatment. Tumor volumes were significantly lower in treated animals 2 and 3 days posttreatment. At the same time points, MRI experiments showed an increase in both 23Na SI and water ADC in treated tumors, whereas control tumors did not show any significant changes. The correlation between 23Na SI and water ADC changes was dramatically increased in the Cp-treated group, suggesting that the observed increases in 23Na SI and water ADC were caused by the same mechanism. Histologic sections showed decreased cell density in the regions of increased 23Na and water ADC SI. Destructive chemical analysis showed that Cp treatment increased the relative extracellular space and tumor [Na+]. We conclude that the changes in water ADC and 23Na SI were largely due to an increase in extracellular space. 23Na MRI and 1H water ADC measurements may provide valuable noninvasive techniques for monitoring chemotherapeutic responses. PMID:16026645

Development and characterization of a eukaryotic expression system for human type II procollagen.

PubMed

Wieczorek, Andrew; Rezaei, Naghmeh; Chan, Clara K; Xu, Chuan; Panwar, Preety; Brömme, Dieter; Merschrod S, Erika F; Forde, Nancy R

2015-12-15

Triple helical collagens are the most abundant structural protein in vertebrates and are widely used as biomaterials for a variety of applications including drug delivery and cellular and tissue engineering. In these applications, the mechanics of this hierarchically structured protein play a key role, as does its chemical composition. To facilitate investigation into how gene mutations of collagen lead to disease as well as the rational development of tunable mechanical and chemical properties of this full-length protein, production of recombinant expressed protein is required. Here, we present a human type II procollagen expression system that produces full-length procollagen utilizing a previously characterized human fibrosarcoma cell line for production. The system exploits a non-covalently linked fluorescence readout for gene expression to facilitate screening of cell lines. Biochemical and biophysical characterization of the secreted, purified protein are used to demonstrate the proper formation and function of the protein. Assays to demonstrate fidelity include proteolytic digestion, mass spectrometric sequence and posttranslational composition analysis, circular dichroism spectroscopy, single-molecule stretching with optical tweezers, atomic-force microscopy imaging of fibril assembly, and transmission electron microscopy imaging of self-assembled fibrils. Using a mammalian expression system, we produced full-length recombinant human type II procollagen. The integrity of the collagen preparation was verified by various structural and degradation assays. This system provides a platform from which to explore new directions in collagen manipulation.

RIP1-mediated mitochondrial dysfunction and ROS production contributed to tumor necrosis factor alpha-induced L929 cell necroptosis and autophagy.

PubMed

Ye, Yuan-Chao; Wang, Hong-Ju; Yu, Lu; Tashiro, Shin-Ichi; Onodera, Satoshi; Ikejima, Takashi

2012-12-01

Tumor necrosis factor alpha (TNFα) induces necroptosis and autophagy; however, the detailed molecular mechanism is not fully understood. In this study, we found that TNFα administration caused mitochondrial dysfunction and reactive oxygen species (ROS) production, which led to necroptosis and autophagy in murine fibrosarcoma L929 cells. Notably, the RIP1 (serine-threonine kinase receptor-interacting protein 1, a main adaptor protein of necroptosis) specific inhibitor necrostatin-1 (Nec-1) recovered mitochondrial dysfunction and ROS production due to TNFα administration. Moreover, pan-caspase inhibitor z-VAD-fmk (zVAD) increased RIP1 expression and exacerbated TNFα-induced mitochondrial dysfunction and ROS production, indicating that RIP1 led to mitochondrial dysfunction and ROS production. In addition, cytochrome c release from mitochondria was accompanied with TNFα administration, and Nec-1 blocked the release of cytochrome c upon TNFα administration, while zVAD enhanced the release. These further suggested that RIP1 induced mitochondrial dysfunction accompanied with cytochrome c release. Furthermore, autophagy inhibitor 3-methyladenine (3MA) did not affect RIP1 expression as well as mitochondrial dysfunction and ROS production. Together with our previous publication that autophagy was a downstream consequence of necroptosis, we concluded that TNFα induced mitochondrial dysfunction accompanied with ROS production and cytochrome c release via RIP1, leading to necroptosis and resulting autophagic cell death. Copyright © 2012 Elsevier B.V. All rights reserved.

Potential of activatable FAP-targeting immunoliposomes in intraoperative imaging of spontaneous metastases.

PubMed

Tansi, Felista L; Rüger, Ronny; Böhm, Claudia; Kontermann, Roland E; Teichgraeber, Ulf K; Fahr, Alfred; Hilger, Ingrid

2016-05-01

Despite intensive research and medical advances met, metastatic disease remains the most common cause of death in cancer patients. This results from late diagnosis, poor therapeutic response and undetected micrometastases and tumor margins during surgery. One approach to overcome these challenges involves fluorescence imaging, which exploits the properties of fluorescent probes for diagnostic detection of molecular structures at the onset of transformation and for intraoperative detection of metastases and tumor margins in real time. Considering these benefits, many contrast agents suitable for fluorescence imaging have been reported. However, most reports only demonstrate the detection of primary tumors and not the detection of metastases or their application in models of image-guided surgery. In this work, we demonstrate the influence of fibroblast activation protein (FAP) on the metastatic potential of fibrosarcoma cells and elucidate the efficacy of activatable FAP-targeting immunoliposomes (FAP-IL) for image-guided detection of the spontaneous metastases in mice models. Furthermore, we characterized the biodistribution and cellular localization of the liposomal fluorescent components in mice organs and traced their excretion over time in urine and feces. Taken together, activatable FAP-IL enhances intraoperative imaging of metastases. Their high accumulation in metastases, subsequent localization in the bile canaliculi and liver kupffer cells and suitable excretion in feces substantiates their potency as contrast agents for intraoperative imaging. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Surgical Management of Head and Neck Soft Tissue Sarcoma: 11-Year Experience at a Tertiary Care Centre in South India.

PubMed

Sharma, Nivedita; George, Nebu Abraham; Singh, Rajesh; Iype, Elizabeth Mathew; Varghese, Bipin T; Thomas, Shaji

2018-06-01

Head and neck soft tissue sarcoma (HNSTS) is a rare neoplasm accounting for 1% of all head and neck tumours. Because of rarity and varied biological behaviour among various subtypes, knowledge about these tumours is limited. This study aimed at analysing clinicopathological, recurrence and survival pattern of surgically treated HNSTS. Case records of 28 patients of HNSTS who underwent surgery at the Regional Cancer Centre (RCC), Trivandrum (India) between 2002 and 2012 were analysed retrospectively for demographic profile, clinical features, treatment given, recurrence pattern and outcome. The median age of patients was 37 years (range, 3-79) with male:female ratio of 3:2. Majority of patients presented with painless lump in the neck as the most common subsite affected followed by scalp and face. One patient had nodal disease, while none had distant metastasis at presentation. The most frequent histological subtypes were synovial sarcoma and fibrosarcoma followed by malignant fibrous histiocytoma, angiosarcoma and rhabdomyosarcoma. Majority (78.5%) of patients received adjuvant therapy in the form of radiation, chemotherapy or chemo-radiation. After mean follow-up of 49 months, four patients had died, and six developed local recurrence and four distant metastasis. The overall 5-year survival was 82.7% while 5-year disease-free survival was 55.3%. HNSTS is a rare entity that requires multimodality treatment to achieve optimum locoregional control and survival.

Oleanane-type triterpene saponins from Calendula stellata.

PubMed

Lehbili, Meryem; Alabdul Magid, Abdulmagid; Kabouche, Ahmed; Voutquenne-Nazabadioko, Laurence; Abedini, Amin; Morjani, Hamid; Sarazin, Thomas; Gangloff, Sophie C; Kabouche, Zahia

2017-12-01

Five previously undescribed bisdesmosidic triterpenoid saponins named calendustellatosides A-E, along with fifteen known compounds were isolated from the 70% ethanol whole plant extract of Calendula stellata Cav. (Asteraceae). Their structures were determined by 1D- and 2D-NMR spectroscopy as well as high resolution mass spectrometry and acid hydrolysis. The saponins comprised oleanolic acid, echinocystic acid, morolic acid or mesembryanthemoidigenic acid as the aglycones and saccharide moieties at C-3 and C-28. Like most Calendula saponins, the sugar moiety linked at C-3 was either β-d-glucose or β-d-glucuronic acid which could be substituted at C-3 by a β-d-galactose and/or C-2 by a supplementary β-d-galactose or a β-d-glucose. The sugar moiety linked to C-28 was determined as β-d-glucose. The antibacterial evaluation of compounds 1-20 by bioautography on Staphylococcus aureus followed by the determination of MIC values of active compounds by serial dilution technique against 5 bacteria revealed that; calendustellatoside D was the most active against Enterococcus faecalis with an antibacterial effect comparable to antibiotics. The cytotoxic activities of isolated compounds were evaluated against fibrosarcoma cell line (HT1080) and human lung cancer cell line (A549). Calendustellatosides B and D exhibited a low cytotoxic activity against HT1080 cell line with IC 50 values of 47 ± 0.6 and 39 ± 0.5 μM, respectively. Copyright © 2017 Elsevier Ltd. All rights reserved.

A common variant of MAF/c-MAF, transcriptional factor gene in the kidney, is associated with gout susceptibility.

PubMed

Higashino, Toshihide; Matsuo, Hirotaka; Okada, Yukinori; Nakashima, Hiroshi; Shimizu, Seiko; Sakiyama, Masayuki; Tadokoro, Shin; Nakayama, Akiyoshi; Kawaguchi, Makoto; Komatsu, Mako; Hishida, Asahi; Nakatochi, Masahiro; Ooyama, Hiroshi; Imaki, Junko; Shinomiya, Nariyoshi

2018-01-01

Gout is a multifactorial disease characterized by acute inflammatory arthritis, and it is caused as a consequence of hyperuricemia. A recent meta-analysis of genome-wide association studies has newly identified the relationship between serum uric acid (SUA) levels and rs889472, a single nucleotide polymorphism of musculoaponeurotic fibrosarcoma oncogene (MAF/c-MAF). However, it remained unclear whether rs889472 is associated with gout susceptibility. In the present study, we investigate the association between c-MAF rs889472 and gout in Japanese male population. We genotyped 625 male patients who were clinically diagnosed as gout and 1221 male control subjects without hyperuricemia or a history of gout by TaqMan method. As a result, the major allele (C), which reportedly increases SUA levels, had a higher frequency in the gout cases (58.8%) than in the controls (55.0%). A logistic regression analysis showed a significant association between rs889472 and gout (p = 0.029, odds ratio = 1.17; 95% confidence interval 1.02-1.34). C-MAF is reported as a pivotal transcriptional factor in the development and differentiation of renal proximal tubular cells. Because urate is mainly regulated in renal proximal tubular cells, c-MAF may have an important role in urate regulation in the kidney and influence not only SUA but also gout susceptibility. Our finding shows that rs889472 of c-MAF is associated with gout susceptibility.

Significance of abnormal serum binding of insulin-like growth factor II in the development of hypoglycemia in patients with non-islet-cell tumors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Daughaday, W.H.; Kapadia, M.

1989-09-01

The authors reported that serum and tumor from a hypoglycemic patient with a fibrosarcoma contained insulin-like growth factor II (IGF-II), mostly in a large molecular form designated big IGF-II. They now describe two additional patients with non-islet-cell tumor with hypoglycemia (NICTH) whose sera contained big IGF-II. Removal of the tumor eliminated most of the big IGF-II from the sera of two patients. Because specific IGF-binding proteins modify the bioactivity of IGFs, the sizes of the endogenous IGF-binding protein complexes were determined after neutral gel filtration through Sephadex G-200. Normally about 75% of IGFs are carried as a ternary complex ofmore » 150 kDa consisting of IGF, a growth hormone (GH)-dependent IGF-binding protein, and an acid-labile complexing component. The three patients with NICTH completely lacked the 150-kDa complex. IGF-II was present as a 60-kDa complex with variable contributions of smaller complexes. In the immediate postoperative period, a 110-kDa complex appeared rather than the expected 150-kDa complex. Abnormal IGF-II binding may be important in NICTH because the 150-kDa complexes cross the capillary membrane poorly. The smaller complexes present in our patients' sera would be expected to enter interstitial fluid readily, and a 4- to 5-fold increase in the fraction of IGFs reaching the target cells would result.« less

Separation of replication and transcription domains in nucleoli.

PubMed

Smirnov, E; Borkovec, J; Kováčik, L; Svidenská, S; Schröfel, A; Skalníková, M; Švindrych, Z; Křížek, P; Ovesný, M; Hagen, G M; Juda, P; Michalová, K; Cardoso, M C; Cmarko, D; Raška, I

2014-12-01

In mammalian cells, active ribosomal genes produce the 18S, 5.8S and 28S RNAs of ribosomal particles. Transcription levels of these genes are very high throughout interphase, and the cell needs a special strategy to avoid collision of the DNA polymerase and RNA polymerase machineries. To investigate this problem, we measured the correlation of various replication and transcription signals in the nucleoli of HeLa, HT-1080 and NIH 3T3 cells using a specially devised software for analysis of confocal images. Additionally, to follow the relationship between nucleolar replication and transcription in living cells, we produced a stable cell line expressing GFP-RPA43 (subunit of RNA polymerase I, pol I) and RFP-PCNA (the sliding clamp protein) based on human fibrosarcoma HT-1080 cells. We found that replication and transcription signals are more efficiently separated in nucleoli than in the nucleoplasm. In the course of S phase, separation of PCNA and pol I signals gradually increased. During the same period, separation of pol I and incorporated Cy5-dUTP signals decreased. Analysis of single molecule localization microscopy (SMLM) images indicated that transcriptionally active FC/DFC units (i.e. fibrillar centers with adjacent dense fibrillar components) did not incorporate DNA nucleotides. Taken together, our data show that replication of the ribosomal genes is spatially separated from their transcription, and FC/DFC units may provide a structural basis for that separation. Copyright © 2014 Elsevier Inc. All rights reserved.

Improving Sensitivity in Ultrasound Molecular Imaging by Tailoring Contrast Agent Size Distribution: In Vivo Studies

PubMed Central

Streeter, Jason E.; Gessner, Ryan; Miles, Iman; Dayton, Paul A.

2010-01-01

Molecular imaging with ultrasound relies on microbubble contrast agents (MCAs) selectively adhering to a ligand-specific target. Prior studies have shown that only small quantities of microbubbles are retained at their target sites, therefore, enhancing contrast sensitivity to low concentrations of microbubbles is essential to improve molecular imaging techniques. In order to assess the effect of MCA diameter on imaging sensitivity, perfusion and molecular imaging studies were performed with microbubbles of varying size distributions. To assess signal improvement and MCA circulation time as a function of size and concentration, blood perfusion was imaged in rat kidneys using nontargeted size-sorted MCAs with a Siemens Sequoia ultrasound system (Siemans, Mountain View, CA) in cadence pulse sequencing (CPS) mode. Molecular imaging sensitivity improvements were studied with size-sorted αvβ3-targeted bubbles in both fibrosarcoma and R3230 rat tumor models. In perfusion imaging studies, video intensity and contrast persistence was ≈8 times and ≈3 times greater respectively, for “sorted 3-micron” MCAs (diameter, 3.3 ± 1.95 μm) when compared to “unsorted” MCAs (diameter, 0.9 ± 0.45 μm) at low concentrations. In targeted experiments, application of sorted 3-micron MCAs resulted in a ≈20 times video intensity increase over unsorted populations. Tailoring size-distributions results in substantial imaging sensitivity improvement over unsorted populations, which is essential in maximizing sensitivity to small numbers of MCAs for molecular imaging. PMID:20236606

Neutrophils responsive to endogenous IFN-beta regulate tumor angiogenesis and growth in a mouse tumor model.

PubMed

Jablonska, Jadwiga; Leschner, Sara; Westphal, Kathrin; Lienenklaus, Stefan; Weiss, Siegfried

2010-04-01

Angiogenesis is a hallmark of malignant neoplasias, as the formation of new blood vessels is required for tumors to acquire oxygen and nutrients essential for their continued growth and metastasis. However, the signaling pathways leading to tumor vascularization are not fully understood. Here, using a transplantable mouse tumor model, we have demonstrated that endogenous IFN-beta inhibits tumor angiogenesis through repression of genes encoding proangiogenic and homing factors in tumor-infiltrating neutrophils. We determined that IFN-beta-deficient mice injected with B16F10 melanoma or MCA205 fibrosarcoma cells developed faster-growing tumors with better-developed blood vessels than did syngeneic control mice. These tumors displayed enhanced infiltration by CD11b+Gr1+ neutrophils expressing elevated levels of the genes encoding the proangiogenic factors VEGF and MMP9 and the homing receptor CXCR4. They also expressed higher levels of the transcription factors c-myc and STAT3, known regulators of VEGF, MMP9, and CXCR4. In vitro, treatment of these tumor-infiltrating neutrophils with low levels of IFN-beta restored expression of proangiogenic factors to control levels. Moreover, depletion of these neutrophils inhibited tumor growth in both control and IFN-beta-deficient mice. We therefore suggest that constitutively produced endogenous IFN-beta is an important mediator of innate tumor surveillance. Further, we believe our data help to explain the therapeutic effect of IFN treatment during the early stages of cancer development.

Targeting tumor antigens to secreted membrane vesicles in vivo induces efficient antitumor immune responses.

PubMed

Zeelenberg, Ingrid S; Ostrowski, Matias; Krumeich, Sophie; Bobrie, Angélique; Jancic, Carolina; Boissonnas, Alexandre; Delcayre, Alain; Le Pecq, Jean-Bernard; Combadière, Béhazine; Amigorena, Sebastian; Théry, Clotilde

2008-02-15

Expression of non-self antigens by tumors can induce activation of T cells in vivo, although this activation can lead to either immunity or tolerance. CD8+ T-cell activation can be direct (if the tumor expresses MHC class I molecules) or indirect (after the capture and cross-presentation of tumor antigens by dendritic cells). The modes of tumor antigen capture by dendritic cells in vivo remain unclear. Here we examine the immunogenicity of the same model antigen secreted by live tumors either in association with membrane vesicles (exosomes) or as a soluble protein. We have artificially addressed the antigen to secreted vesicles by coupling it to the factor VIII-like C1C2 domain of milk fat globule epidermal growth factor-factor VIII (MFG-E8)/lactadherin. We show that murine fibrosarcoma tumor cells that secrete vesicle-bound antigen grow slower than tumors that secrete soluble antigen in immunocompetent, but not in immunodeficient, host mice. This growth difference is due to the induction of a more potent antigen-specific antitumor immune response in vivo by the vesicle-bound than by the soluble antigen. Finally, in vivo secretion of the vesicle-bound antigen either by tumors or by vaccination with naked DNA protects against soluble antigen-secreting tumors. We conclude that the mode of secretion can determine the immunogenicity of tumor antigens and that manipulation of the mode of antigen secretion may be used to optimize antitumor vaccination protocols.

Antigen localization controls T cell-mediated tumor immunity.

PubMed

Zeelenberg, Ingrid S; van Maren, Wendy W C; Boissonnas, Alexandre; Van Hout-Kuijer, Maaike A; Den Brok, Martijn H M G M; Wagenaars, Jori A L; van der Schaaf, Alie; Jansen, Eric J R; Amigorena, Sebastian; Théry, Clotilde; Figdor, Carl G; Adema, Gosse J

2011-08-01

Effective antitumor immunotherapy requires the identification of suitable target Ags. Interestingly, many of the tumor Ags used in clinical trials are present in preparations of secreted tumor vesicles (exosomes). In this study, we compared T cell responses elicited by murine MCA101 fibrosarcoma tumors expressing a model Ag at different localizations within the tumor cell in association with secreted vesicles (exosomes), as a nonsecreted cell-associated protein, or as secreted soluble protein. Remarkably, we demonstrated that only the tumor-secreting vesicle-bound Ag elicited a strong Ag-specific CD8(+) T cell response, CD4(+) T cell help, Ag-specific Abs, and a decrease in the percentage of immunosuppressive regulatory T cells in the tumor. Moreover, in a therapeutic tumor model of cryoablation, only in tumors secreting vesicle-bound Ag could Ag-specific CD8(+) T cells still be detected up to 16 d after therapy. We concluded that the localization of an Ag within the tumor codetermines whether a robust immunostimulatory response is elicited. In vivo, vesicle-bound Ag clearly skews toward a more immunogenic phenotype, whereas soluble or cell-associated Ag expression cannot prevent or even delay outgrowth and results in tumor tolerance. This may explain why particular immunotherapies based on these vesicle-bound tumor Ags are potentially successful. Therefore, we conclude that this study may have significant implications in the discovery of new tumor Ags suitable for immunotherapy and that their location should be taken into account to ensure a strong antitumor immune response.

Angiopoietin-4 increases permeability of blood vessels and promotes lymphatic dilation.

PubMed

Kesler, Cristina T; Pereira, Ethel R; Cui, Cheryl H; Nelson, Gregory M; Masuck, David J; Baish, James W; Padera, Timothy P

2015-09-01

The angiopoietin (Ang) ligands are potential therapeutic targets for lymphatic related diseases, which include lymphedema and cancer. Ang-1 and Ang-2 functions are established, but those of Ang-4 are poorly understood. We used intravital fluorescence microscopy to characterize Ang-4 actions on T241 murine fibrosarcoma-associated vessels in mice. The diameters of lymphatic vessels draining Ang-4- or VEGF-C (positive control)-expressing tumors increased to 123 and 135 μm, respectively, and parental, mock-transduced (negative controls) and tumors expressing Ang-1 or Ang-2 remained at baseline (∼60 μm). Ang-4 decreased human dermal lymphatic endothelial cell (LEC) monolayer permeability by 27% while increasing human dermal blood endothelial cell (BEC) monolayer permeability by 200%. In vivo, Ang-4 stimulated a 4.5-fold increase in tumor-associated blood vessel permeability compared with control when measured using intravital quantitative multiphoton microscopy. Ang-4 activated receptor signaling in both LECs and BECs, evidenced by tyrosine kinase with Ig and endothelial growth factor homology domains-2 (TIE2) receptor, protein kinase B, and Erk1,2 phosphorylation detectable by immunoblotting. These data suggest that Ang-4 actions are mediated through cell-type-specific networks and that lymphatic vessel dilation occurs secondarily to increased vascular leakage. Ang-4 also promoted survival of LECs. Thus, blocking Ang-4 may prune the draining lymphatic vasculature and decrease interstitial fluid pressure (IFP) by reducing vascular permeability. © FASEB.

Spatiotemporal autophagic degradation of oxidatively damaged organelles after photodynamic stress is amplified by mitochondrial reactive oxygen species

PubMed Central

Rubio, Noemi; Coupienne, Isabelle; Di Valentin, Emmanuel; Heirman, Ingeborg; Grooten, Johan; Piette, Jacques; Agostinis, Patrizia

2012-01-01

Although reactive oxygen species (ROS) have been reported to evoke different autophagic pathways, how ROS or their secondary products modulate the selective clearance of oxidatively damaged organelles is less explored. To investigate the signaling role of ROS and the impact of their compartmentalization in autophagy pathways, we used murine fibrosarcoma L929 cells overexpressing different antioxidant enzymes targeted to the cytosol or mitochondria and subjected them to photodynamic (PD) stress with the endoplasmic reticulum (ER)-associated photosensitizer hypericin. We show that following apical ROS-mediated damage to the ER, predominantly cells overexpressing mitochondria-associated glutathione peroxidase 4 (GPX4) and manganese superoxide dismutase (SOD2) displayed attenuated kinetics of autophagosome formation and overall cell death, as detected by computerized time-lapse microscopy. Consistent with a primary ER photodamage, kinetics and colocalization studies revealed that photogenerated ROS induced an initial reticulophagy, followed by morphological changes in the mitochondrial network that preceded clearance of mitochondria by mitophagy. Overexpression of cytosolic and mitochondria-associated GPX4 retained the tubular mitochondrial network in response to PD stress and concomitantly blocked the progression toward mitophagy. Preventing the formation of phospholipid hydroperoxides and H2O2 in the cytosol as well as in the mitochondria significantly reduced cardiolipin peroxidation and apoptosis. All together, these results show that in response to apical ER photodamage ROS propagate to mitochondria, which in turn amplify ROS production, thereby contributing to two antagonizing processes, mitophagy and apoptosis. PMID:22889744

Alpinia officinarum Stimulates Osteoblast Mineralization and Inhibits Osteoclast Differentiation.

PubMed

Shim, Ki-Shuk; Lee, Chung-Jo; Yim, Nam-Hui; Gu, Min Jung; Ma, Jin Yeul

2016-01-01

Alpinia officinarum rhizome has been used as a traditional herbal remedy to treat inflammatory and internal diseases. Based on the previously observed inhibitory effect of A. officinarum rhizome in an arthritis model, we evaluated whether a water extract of A. officinarum rhizome (WEAO) would enhance in vitro osteoblast mineralization using calvarial osteoblast precursor cells or would inhibit in vitro osteoclast differentiation and bone resorption using bone marrow derived macrophages. In osteoblasts, WEAO enhanced the mRNA levels of transcription factor (runt-related transcription factor 2, smad1, smad5, and junB) and marker (bone morphogenetic protein-2, collagen type 1alpha1, and osteocalcin) genes related to osteoblast mineralization, consistent with increased alizarin red S staining intensity. WEAO markedly inhibited osteoclast differentiation by suppressing the receptor activator for nuclear factor-[Formula: see text]B ligand-induced downregulation of inhibitor of DNA binding 2 and V-maf musculoaponeurotic fibrosarcoma oncogene homolog B and the phosphorylation of c-Jun N-terminal kinase, p38, nuclear factor-[Formula: see text]B, c-Src, and Bruton's tyrosine kinase to induce nuclear factor of activated T cells cytoplasmic 1 expression. WEAO also suppressed the resorbing activity of mature osteoclasts by altering actin ring formation. Therefore, the results of this study demonstrate that WEAO stimulates osteoblast mineralization and inhibits osteoclast differentiation. Thus, WEAO may be a promising herbal candidate to treat or prevent pathological bone diseases by regulating the balance between osteoclast and osteoblast activity.

Dosimetry study of PHOTOFRIN-mediated photodynamic therapy in a mouse tumor model

NASA Astrophysics Data System (ADS)

Qiu, Haixia; Kim, Michele M.; Penjweini, Rozhin; Zhu, Timothy C.

2016-03-01

It is well known in photodynamic therapy (PDT) that there is a large variability between PDT light dose and therapeutic outcomes. An explicit dosimetry model using apparent reacted 1O2 concentration [1O2]rx has been developed as a PDT dosimetric quantity to improve the accuracy of the predicted ability of therapeutic efficacy. In this study, this explicit macroscopic singlet oxygen model was adopted to establish the correlation between calculated reacted [1O2]rx and the tumor growth using Photofrin-mediated PDT in a mouse tumor model. Mice with radiation-induced fibrosarcoma (RIF) tumors were injected with Photofrin at a dose of 5 mg/kg. PDT was performed 24h later with different fluence rates (50, 75 and 150 mW/cm2) and different fluences (50 and 135 J/cm2) using a collimated light applicator coupled to a 630nm laser. The tumor volume was monitored daily after PDT and correlated with the total light fluence and [1O2]rx. Photophysical parameters as well as the singlet oxygen threshold dose for this sensitizer and the RIF tumor model were determined previously. The result showed that tumor growth rate varied greatly with light fluence for different fluence rates while [1O2]rx had a good correlation with the PDT-induced tumor growth rate. This preliminary study indicated that [1O2]rx could serve as a better dosimetric predictor for predicting PDT outcome than PDT light dose.

Characteristics of the antitumor activities in tumor cells and modulation of the inflammatory response in RAW264.7 cells of a novel antimicrobial peptide, chrysophsin-1, from the red sea bream (Chrysophrys major).

PubMed

Hsu, Jung-Chieh; Lin, Li-Ching; Tzen, Jason T C; Chen, Jyh-Yih

2011-05-01

The antimicrobial peptide, chrysophsin-1, exhibits antimicrobial activities with similar efficiencies for both gram-negative and gram-positive bacteria. In this study, we examined the antitumor activity and modulation of the inflammatory response of a synthetic chrysophsin-1 peptide. In vitro results showed that chrysophsin-1 had greater inhibitory effects against human fibrosarcoma (HT-1080), histiocytic lymphoma (U937), and epithelial carcinoma (HeLa) cells. LDH release by HeLa cells was comparable to that of an MTS assay after treatment with 1.5-3 μg/ml chrysophsin-1 for 24h. Under SEM and TEM observations, we found no intact cell membranes after chrysophsin-1 treatment of HeLa cells for 8h. The suggested mechanism of the cytotoxic activity of chrysophsin-1 was disruption of cancer cell membranes. In addition, we also examined caspase-3, -8, and -9 activities by Western blotting; the results excluded the participation of apoptosis in chrysophsin-1's effect on HeLa cells. Stimulation by lipopolysaccharide induced tumor necrosis factor (TNF)-α which was able to modulate chrysophsin-1 treatment of RAW264.7 cells and inhibited endogenous TNF-α release but did not block its secretion. With data from this study, we demonstrate that chrysophsin-1 has antimicrobial and antitumor activities and modulates the inflammatory response in RAW264.7 cells. Copyright © 2011 Elsevier Inc. All rights reserved.

Decursinol angelate blocks transmigration and inflammatory activation of cancer cells through inhibition of PI3K, ERK and NF-kappaB activation.

PubMed

Kim, Won-Jung; Lee, Min-Young; Kim, Jung-Hee; Suk, Kyoungho; Lee, Won-Ha

2010-10-01

Inflammation is known to be closely associated with the development of cancer. Decursinol angelate (DA), a coumarin compound isolated from Angelica gigas and related compounds have been shown to possess potent anti-inflammatory activities. However, little is known about their effects on the inflammatory processes associated with cancer. In this study, the anti-inflammatory effect of DA was evaluated in cancer cell lines with respect to cellular invasion through the extracellular matrix (ECM) and the expression of pro-inflammatory mediators such as cytokine, cell adhesion molecules and matrix metalloproteinase (MMP)-9. DA inhibited the invasion of fibrosarcoma cell line, HT1080 and breast cancer cell line, MDA-MB-231 in the Matrigel invasion assay. DA-mediated suppression of cancer cell invasion was accomplished by suppression of PI3K activity known to be associated with cytoskeletal rearrangement related to cellular migration. DA also suppressed the adhesion of cancer cells to ECM mediated by down-regulation of beta(1)-integrin expression levels. Furthermore, DA inhibited the expression of pro-inflammatory cytokines and MMP-9 through suppression of PI3K, ERK and NF-kappaB activation. These results demonstrate that DA suppresses invasion and inflammatory activation of cancer cells through modulation of PI3K/AKT, ERK and NF-kappaB. These anti-inflammatory activities of DA may contribute to its anti-cancer activity. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ward, W.; Molteni, A.; Ts'ao, C.

The severity of epilation and moist desquamation, and the incidence of cutaneous tumors were determined in male rats up to 52 weeks after exposure to a range of single doses (0-30 Gy) of gamma rays to the right hemithorax. Half of each radiation dose group consumed control feed, and half consumed feed containing 0.1% (w/w) of the angiotensin converting enzyme inhibitor Captopril (50 mg/kg/day) continuously after irradiation. Rats exposed to 10 Gy exhibited a mild and transient epilation, but no moist desquamation or neoplasms in the radiation port. In animals exposed to 30 Gy, however, epilation began at 2 weeksmore » after irradiation, reached a peak at 7 weeks, then persisted through 52 weeks. Captopril has no effect on the epilation reaction. Two waves of moist desquamation were observed after 30 Gy. The first appeared at 3 weeks after irradiation, reached a peak from 6-10 weeks, then subsided from 12-26 weeks. The second wave of moist desquamation began at 26-28 weeks, and occasionally was accompanied by the appearance of tumors in the radiation port. Captopril reduced the severity of both phases of moist desquamation, and decreased the incidence of tumors. Of the 14 tumors detected in 128 rats exposed to 20 or 30 Gy, all were fibrosarcomas or squamous cell carcinomas, and only 3 occurred in rats receiving Captopril. Multiple tumors (3 cases), tumors induced by 20 Gy (3 cases), and tumors appearing before 26 weeks (1 case) were observed only in rats consuming control diet, not in Captopril-treated rats.« less

A homozygous founder missense variant in arylsulfatase G abolishes its enzymatic activity causing atypical Usher syndrome in humans.

PubMed

Khateb, Samer; Kowalewski, Björn; Bedoni, Nicola; Damme, Markus; Pollack, Netta; Saada, Ann; Obolensky, Alexey; Ben-Yosef, Tamar; Gross, Menachem; Dierks, Thomas; Banin, Eyal; Rivolta, Carlo; Sharon, Dror

2018-01-04

PurposeWe aimed to identify the cause of disease in patients suffering from a distinctive, atypical form of Usher syndrome.MethodsWhole-exome and genome sequencing were performed in five patients from three families of Yemenite Jewish origin, suffering from distinctive retinal degeneration phenotype and sensorineural hearing loss. Functional analysis of the wild-type and mutant proteins was performed in human fibrosarcoma cells.ResultsWe identified a homozygous founder missense variant, c.133G>T (p.D45Y) in arylsulfatase G (ARSG). All patients shared a distinctive retinal phenotype with ring-shaped atrophy along the arcades engirdling the fovea, resulting in ring scotoma. In addition, patients developed moderate to severe sensorineural hearing loss. Both vision and hearing loss appeared around the age of 40 years. The identified variant affected a fully conserved amino acid that is part of the catalytic site of the enzyme. Functional analysis of the wild-type and mutant proteins showed no basal activity of p.D45Y.ConclusionHomozygosity for ARSG-p.D45Y in humans leads to protein dysfunction, causing an atypical combination of late-onset Usher syndrome. Although there is no evidence for generalized clinical manifestations of lysosomal storage diseases in this set of patients, we cannot rule out the possibility that mild and late-onset symptoms may appear.GENETICS in MEDICINE advance online publication, 4 January 2018; doi:10.1038/gim.2017.227.

The photodynamic response of two rodent tumour models to four zinc (II)-substituted phthalocyanines.

PubMed Central

Cruse-Sawyer, J. E.; Griffiths, J.; Dixon, B.; Brown, S. B.

1998-01-01

Four novel zinc (II)-substituted phthalocyanines, varying in charge and hydrophobicity, were evaluated in vivo as new photosensitizers for photodynamic therapy. Two rat tumours with differing vascularity were used: a mammary carcinoma (LMC1) and a fibrosarcoma (LSBD1), with vascular components six times higher in the latter (10.8%+/-1.5) than in the former (1.8%+/-1.4). Each sensitizer was assessed for tumour response relative to normal tissue damage, and optimum doses were selected for further study, ranging from 0.5 to 20 mg kg(-1). Interstitial illumination of the tumours was carried out using a 200-microm-core optical fibre with a 0.5 cm length of diffusing tip, at either 680 or 692 nm, depending on the sensitizer. Light doses of between 200 and 600 J were delivered at a rate of 100 mW from the 0.5-cm diffusing section of the fibre. Maximum mean growth delays ranged from 9 to 13.5 days depending on sensitizer and type of tumour, with the most potent photosensitizer appearing to be the cationic compound. Histopathological changes were investigated after treatment to determine the mechanism by which tumour necrosis was effected. The tumours had the appearance of an infarct and, under the conditions used, the observed damage was shown to be mainly due to ischaemic processes, although some direct tumour cell damage could not be ruled out. Images Figure 4 Figure 5 PMID:9528842

Opto-injection into single living cells by femtosecond near-infrared laser

NASA Astrophysics Data System (ADS)

Peng, Cheng

This dissertation presents a novel technique to deliver membrane impermeable molecules into single living cells with the assistance of femtosecond (fs) near-infrared (NIR) laser pulses. This approach merges ultrafast laser technology with key biological, biomedical, and medical applications, such as gene transfection, gene therapy and drug delivery. This technique promises several major advantages, namely, very high transfection efficiency, high cell survival rate (≈100%) and fully preserved cell viabilities. It is also a promising method to deliver molecules into cells that are difficult or even completely resistant to established physical methods, such as microinjection by glass pipettes, electroporation, and biolistics. In this work, the system for fs NIR opto-injection was designed and built. Successful fs NIR opto-injection has been performed on several cell systems including single mammalian cells (bovine aortic endothelial cells), marine animal eggs (Spisula solidissima oocytes), and human cancer cells (fibrosarcoma HT1080) cultured in a tissue-like environment. The connections between laser parameters and cell responses were explored through further experiments and in-depth analyses, especially the relationship between dye uptake rate and incident laser intensity, and the relationship between pore size created on cell membranes and incident laser intensity. Dye uptake rate of the target cells was observed to depend on incident laser intensity. Pore size was found dependent on incident laser intensity. The conclusion was made that laser-induced breakdown and plasma-induced ablation in cell membrane are the physical principles that govern the process of fs NIR opto-injection.

Two-dimensional zymography differentiates gelatinase isoforms in stimulated microglial cells and in brain tissues of acute brain injuries.

PubMed

Chen, Shanyan; Meng, Fanjun; Chen, Zhenzhou; Tomlinson, Brittany N; Wesley, Jennifer M; Sun, Grace Y; Whaley-Connell, Adam T; Sowers, James R; Cui, Jiankun; Gu, Zezong

2015-01-01

Excessive activation of gelatinases (MMP-2/-9) is a key cause of detrimental outcomes in neurodegenerative diseases. A single-dimension zymography has been widely used to determine gelatinase expression and activity, but this method is inadequate in resolving complex enzyme isoforms, because gelatinase expression and activity could be modified at transcriptional and posttranslational levels. In this study, we investigated gelatinase isoforms under in vitro and in vivo conditions using two-dimensional (2D) gelatin zymography electrophoresis, a protocol allowing separation of proteins based on isoelectric points (pI) and molecular weights. We observed organomercuric chemical 4-aminophenylmercuric acetate-induced activation of MMP-2 isoforms with variant pI values in the conditioned medium of human fibrosarcoma HT1080 cells. Studies with murine BV-2 microglial cells indicated a series of proform MMP-9 spots separated by variant pI values due to stimulation with lipopolysaccharide (LPS). The MMP-9 pI values were shifted after treatment with alkaline phosphatase, suggesting presence of phosphorylated isoforms due to the proinflammatory stimulation. Similar MMP-9 isoforms with variant pI values in the same molecular weight were also found in mouse brains after ischemic and traumatic brain injuries. In contrast, there was no detectable pI differentiation of MMP-9 in the brains of chronic Zucker obese rats. These results demonstrated effective use of 2D zymography to separate modified MMP isoforms with variant pI values and to detect posttranslational modifications under different pathological conditions.

In Situ Lipidization as a New Approach for the Design of a Self Microemulsifying Drug Delivery System (SMEDDS) of Doxorubicin Hydrochloride for Oral Administration.

PubMed

Derajram M Benival, M; Devarajan, Padma V

2015-05-01

The present paper reports in situ lipidization as a novel approach for the design of Dox-self microemulsifying drug delivery system (SMEDDS). Dox-aerosol OT (AOT) ion pair complex (lipidized Dox), exhibited high log P value of 1.74, indicating lipophilic nature. The lipidized Dox revealed good solubility but limited stability in various oils. Rapid complex formation of Dox with AOT dissolved in oils, and the high partitioning of lipidized Dox (-90%) into the oily phase presented in situ lipidization as a strategy to overcome the limited chemical stability of lipidized Dox. SMEDDS was prepared by mixing the lipidizing agent AOT, the surfactant α-Tocopheryl-Polyethyleneglycol-1 000-Succinate (TPGS) and Capmul as the oil. Dox was suspended in the SMEDDS to obtain Dox-SMEDDS. Dox-SMEDDS on aqueous dilution, resulted in a microemulsion with globule size 196 ± 16.56 nm, and revealed slow release of Dox. Oral bioavailability study in rats revealed a 420% enhancement from Dox-SMEDDS compared to Dox solution. Dox-SMEDDS and control group revealed comparable superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) levels in heart and kidneys suggesting safety of the Dox-SMEDDS. Efficacy study (tumor size reduction) in fibrosarcoma mouse model suggested Dox-SMEDDS as a promising oral delivery system for the treatment of cancer. In situ lipidization of Dox in SMEDDS presents a novel approach for the design of an orally bioavailable and promising formulation of Dox for oral administration.

Intraoperative versus postoperative electrochemotherapy in high grade soft tissue sarcomas: a preliminary study in a spontaneous feline model.

PubMed

Spugnini, Enrico P; Baldi, Alfonso; Vincenzi, Bruno; Bongiorni, Franco; Bellelli, Corrado; Citro, Gennaro; Porrello, Alessandro

2007-02-01

Feline soft tissue sarcomas are spontaneous, rapidly growing, and aggressive neoplasms that mimic their human counterpart. The purpose of this study was to evaluate the feasibility and efficacy of electrochemotherapy (ECT) in an adjuvant fashion for the treatment of feline sarcomas, and the possibility of repeated treatments in the case of recurrence. Cats with fibrosarcoma (FSA) were assigned to receive surgery or surgery plus ECT. Feline patients recruited in the ECT study were enrolled in a microscopic arm (39 patients) or a macroscopic arm (19 patients) on the basis of their tumor status (absence or presence of gross disease). Patients received local injection of bleomycin followed by bursts of eight biphasic pulses at a voltage of 1,300 V/cm for postoperative and of 800 V/cm for intraoperative treatments. The median time to recurrence was 4 months for cats treated with surgery alone, 19 months for the postoperative cohort, and 12 months for the intraoperative group. Moreover, ten patients with recurring neoplasms were retreated and experienced responses lasting 6 to 28+ months. Side effects were minimal. Of interest, the metastatic rate (1.7%) in our patients was negligible: only one cat had distant spread. The results suggest that ECT is a well tolerated and potentially useful addition to surgery in controlling high-grade sarcomas. On the basis of these results, additional evaluations are warranted in pets and in humans.

Equine nasal and paranasal sinus tumours: part 2: a contribution of 28 case reports.

PubMed

Dixon, P M; Head, K W

1999-05-01

The clinical and pathological findings of 28 cases (27 horses, 1 donkey) of equid sinonasal tumours examined at the Edinburgh Veterinary School are presented and include: seven cases of squamous cell carcinoma (SCC); five adenocarcinomas; three undifferentiated carcinomas; two adenomas; five fibro-osseous and bone tumours; and single cases of ameloblastoma, fibroma, fibrosarcoma, undifferentiated sarcoma, melanoma and lymphosarcoma. The median ages of animals affected with epithelial, and fibro-osseous/bone tumours were 14 and 4 years, respectively. Unilateral purulent or mucopurulent nasal discharge (81% of cases) and gross facial swellings (82% of cases) were the most common presenting signs with sinonasal tumours, with epistaxis recorded in just 23% of cases. Radiology and endoscopy were the most useful ancillary diagnostic techniques. The maxillary area was the most common site of tumour origin, and only three cases were definitively identified as originating in the nasal cavity. Four of the maxillary SCC lesions originated within the nasal cavities or maxillary sinuses, while two originated in the oral cavity. Fourteen of 15 carcinomas, but only two of the 13 remaining tumours, spread to other sites in the head. Only three cases of sinonasal tumour had lymph node metastases, and none had distant metastases. In the long term, surgical treatment with seven malignant tumours was unsuccessful (6 months median survival post-operatively), but was successful with four out of five benign tumours (no regrowth at a median of 4 years post-operatively).

Primary liver tumors in beagle dogs exposed by inhalation to aerosols of plutonium-238 dioxide

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gillett, N.A.; Muggenburg, B.A.; Mewhinney, J.A.

1988-11-01

Primary liver tumors developed in Beagle dogs exposed by inhalation to aerosols of /sup 238/PuO/sub 2/. Initial deposition of /sup 238/PuO/sub 2/ in the respiratory tract was followed by translocation of a portion of the /sup 238/Pu to the liver and skeleton, which resulted in a large dose commitment and tumor risk to all three tissues. In a population of 144 dogs exposed to /sup 238/PuO/sub 2/, 112 dogs died or were killed 4000 days after /sup 238/Pu exposure, 100 dogs had osteosarcoma, and 28 dogs had lung cancers. At increasing times after exposure, however, liver lesions have become moremore » pronounced. Ten primary liver tumors in nine animals were diagnosed in the dogs dying before 4000 days after exposure. An additional five primary liver tumors in three dogs occurred in 9 animals killed after 4000 days after exposure. The majority of these tumors have been fibrosarcomas. The liver tumors were usually not the cause of death, and rarely metastasized. The occurrence of liver tumors in this study indicates that /sup 238/Pu is an effective hepatic carcinogen. Liver carcinogenesis is assuming an increasing importance in this study at late times after inhalation exposure. These results suggest that the liver may be an important organ at risk for the development of neoplasia in humans at time periods long after inhalation of /sup 238/Pu.« less

TAN-1813, a novel Ras-farnesyltransferase inhibitor produced by Phoma sp. taxonomy, fermentation, isolation and biological activities in vitro and in vivo.

PubMed

Ishii, T; Hayashi, K; Hida, T; Yamamoto, Y; Nozaki, Y

2000-08-01

A novel Ras-farnesyltransferase inhibitor designated TAN-1813 was isolated from the culture broth of a fungus strain, FL-41510, isolated as a plant endophyte. The producer was taxonomically characterized as Phoma sp. FL-41510. TAN-1813 inhibited rat brain farnesyltransferase and geranylgeranyltransferase I activity with IC50 values of 23 microg/ml and 47/microg/ml, respectively. TAN-1813 showed mixed-type inhibition with respect to farnesylpyrophosphate and noncompetitive inhibition with respect to a K-Ras C-terminal peptide. It also inhibited the in situ farnesylation of cellular Ras proteins in a K-ras transformant (NIH3T3/K-ras) of mouse embryonic fibroblast cell line NIH3T3. TAN- 1813 inhibited the proliferation of various human cancer cells, some of which harbor activated ras alleles, with IC50 values of 15 approximately 110 ng/ml as well as that of NIH3T3 and NIH3T3/K-ras cells with IC50S of 540 and 310 ng/ml, respectively. Flow cytometric analysis indicated that TAN-1813 arrests NIH3T3/K-ras cells at both G1 and G2/M phases of the cell cycle. In addition, TAN-1813 was found to induce morphological reversion of NIH3T3/K-ras cells from the transformed phenotype. Antitumor activity of TAN-1813 against human fibrosarcoma HT-1080 and NIH3T3/K-ras tumors in nude mice was also verified.

Identification of novel resistance mechanisms to NAMPT inhibition via the de novo NAD+ biosynthesis pathway and NAMPT mutation.

PubMed

Guo, Jun; Lam, Lloyd T; Longenecker, Kenton L; Bui, Mai H; Idler, Kenneth B; Glaser, Keith B; Wilsbacher, Julie L; Tse, Chris; Pappano, William N; Huang, Tzu-Hsuan

2017-09-23

Cancer cells have an unusually high requirement for the central and intermediary metabolite nicotinamide adenine dinucleotide (NAD + ), and NAD + depletion ultimately results in cell death. The rate limiting step within the NAD + salvage pathway required for converting nicotinamide to NAD + is catalyzed by nicotinamide phosphoribosyltransferase (NAMPT). Targeting NAMPT has been investigated as an anti-cancer strategy, and several highly selective small molecule inhibitors have been found to potently inhibit NAMPT in cancer cells, resulting in NAD + depletion and cytotoxicity. To identify mechanisms that could cause resistance to NAMPT inhibitor treatment, we generated a human fibrosarcoma cell line refractory to the highly potent and selective NAMPT small molecule inhibitor, GMX1778. We uncovered novel and unexpected mechanisms of resistance including significantly increased expression of quinolinate phosphoribosyl transferase (QPRT), a key enzyme in the de novo NAD + synthesis pathway. Additionally, exome sequencing of the NAMPT gene in the resistant cells identified a single heterozygous point mutation that was not present in the parental cell line. The combination of upregulation of the NAD + de novo synthesis pathway through QPRT over-expression and NAMPT mutation confers resistance to GMX1778, but the cells are only partially resistant to next-generation NAMPT inhibitors. The resistance mechanisms uncovered herein provide a potential avenue to continue exploration of next generation NAMPT inhibitors to treat neoplasms in the clinic. Copyright © 2017 Elsevier Inc. All rights reserved.

Drinking water disinfection byproduct iodoacetic acid induces tumorigenic transformation of NIH3T3 cells.

PubMed

Wei, Xiao; Wang, Shu; Zheng, Weiwei; Wang, Xia; Liu, Xiaolin; Jiang, Songhui; Pi, Jingbo; Zheng, Yuxin; He, Gengsheng; Qu, Weidong

2013-06-04

Iodoacetic acid (IAA) and iodoform (IF) are unregulated iodinated disinfection byproducts (DBPs) found in drinking water. Their presence in the drinking water of China has not been documented. Recently, the carcinogenic potential of IAA and IF has been a concern because of their mutagenicity in bacteria and genotoxicity in mammalian cells. Therefore, we measured their concentrations in Shanghai drinking water and assessed their cytotoxicity, genotoxicity, and ability to transform NIH3T3 cells to tumorigenic lines. The concentrations of IAA and IF in Shanghai drinking water varied between summer and winter with maximum winter levels of 2.18 μg/L IAA and 0.86 μg/L IF. IAA with a lethal concentration 50 (LC50) of 2.77 μM exhibited more potent cytotoxicity in NIH3T3 cells than IF (LC50 = 83.37 μM). IAA, but not IF, induced a concentration-dependent DNA damage measured by γ-H2AX staining and increased tail moment in single-cell gel electrophoresis. Neither IAA nor IF increased micronucleus frequency. Prolonged exposure of NIH3T3 cells to IAA increased the frequencies of transformed cells with anchorage-independent growth and agglutination with concanavalin A. IAA-transformed cells formed aggressive fibrosarcomas after inoculation into Balb/c nude mice. This study demonstrated that IAA has a biological activity that is consistent with a carcinogen and human exposure should be of concern.

A requirement of dendritic cell-derived interleukin-27 for the tumor infiltration of regulatory T cells.

PubMed

Xia, Siyuan; Wei, Jun; Wang, Jingya; Sun, Huayan; Zheng, Wenting; Li, Yangguang; Sun, Yanbo; Zhao, Huiyuan; Zhang, Song; Wen, Ti; Zhou, Xinglong; Gao, Jian-Xin; Wang, Puyue; Wu, Zhenzhou; Zhao, Liqing; Yin, Zhinan

2014-05-01

Tregs (Foxp3 + CD4 + ) are enriched in tumors to foster a tolerant microenvironment that inhibits antitumor immune response. IL-27 is reported to regulate the development and function of Tregs in vitro and in vivo; however, the effects of endogenous IL-27 on Tregs in the tumor microenvironment remain elusive. We demonstrated that in the absence of DC-derived IL-27, Tregs were decreased significantly in transplanted B16 melanoma, transplanted EL-4 lymphoma, and MCA-induced fibrosarcoma by using IL-27p28 conditional KO mice. Further studies revealed that IL-27 promoted the expression of CCL22, which is established to mediate the recruitment of peripheral Tregs into tumors. Tumor-associated DCs were identified as the major source of CCL22 in tumor sites, and IL-27 could induce CCL22 expression in an IL-27R-dependent manner. Intratumoral reconstitution of rmCCL22 or rmIL-27, but not rmIL-27p28, significantly restored the tumor infiltration of Tregs in IL-27p28 KO mice. Correlated with a decreased number of Tregs, tumor-infiltrating CD4 T cells were found to produce much more IFN-γ in IL-27p28 KO mice, which highlighted the physiological importance of Tregs in suppressing an antitumor immune response. Overall, our results identified a novel mechanism of action of IL-27 on Tregs in the context of cancers. © 2014 Society for Leukocyte Biology.

LUNG INJURY, INFLAMMATION AND AKT SIGNALING FOLLOWING INHALATION OF PARTICULATE HEXAVALENT CHROMIUM

PubMed Central

Beaver, Laura M.; Stemmy, Erik J.; Constant, Stephanie L.; Schwartz, Arnold; Little, Laura G.; Gigley, Jason P.; Chun, Gina; Sugden, Kent D.; Ceryak, Susan M.; Patierno, Steven R.

2013-01-01

Certain particulate hexavalent chromium [Cr(VI)] compounds are human respiratory carcinogens that release genotoxic soluble chromate, and are associated with fibrosis, fibrosarcomas, adenocarcinomas and squamous cell carcinomas of the lung. We postulate that inflammatory processes and mediators may contribute to the etiology of Cr(VI) carcinogenesis, however the immediate (0–24 hours) pathologic injury and immune responses after exposure to particulate chromates have not been adequately investigated. Our aim was to determine the nature of the lung injury, inflammatory response, and survival signaling responses following intranasal exposure of BALB/c mice to particulate basic zinc chromate. Factors associated with lung injury, inflammation and survival signaling were measured in airway lavage fluid and in lung tissue. A single chromate exposure induced an acute immune response in the lung, characterized by a rapid and significant increase in IL-6 and GRO-α levels, an influx of neutrophils, and a decline in macrophages in lung airways. Histological examination of lung tissue in animals challenged with a single chromate exposure revealed an increase in bronchiolar cell apoptosis and mucosal injury. Furthermore, chromate exposure induced injury and inflammation that progressed to alveolar and interstitial pneumonitis. Finally, a single Cr(VI) challenge resulted in a rapid and persistent increase in the number of airways immunoreactive for phosphorylation of the survival signaling protein Akt, on serine 473. These data illustrate that chromate induces both survival signaling and an inflammatory response in the lung, which we postulate may contribute to early oncogenesis. PMID:19109987

WhatsApp is an effective tool for obtaining second opinion in oral pathology practice.

PubMed

Sarode, Sachin C; Sarode, Gargi S; Anand, Rahul; Patil, Shankargouda; Unadkat, Hemant

2017-08-01

The aim of this study was to find out the efficacy of WhatsApp application for obtaining second opinion on histopathological diagnosis in oral pathology practice. A total of 247 cases comprising of 34 different oral pathologies were photomicrographed using smartphone cameras through compound microscopes and sent for second opinion diagnosis (SOD) to 20 different oral pathologists using WhatsApp. Of 4795 (97.06%) total second opinion received, correct SOD were received for 4710 (98.22%) cases. Hundred percent times correct SOD was received for lesions including adenomatoid odontogenic tumor, keratinizing cystic odontogenic tumor, odontome, and dentigerous cyst. Lesions such as myoepithelial carcinoma, osteosarcoma, fibrosarcoma, and intravascular papillary endothelial hyperplasia received less percentage of correct SOD (85.71-75.75%). Correct SOD was obtained for variants of ameloblastoma (99.01%), grading of epithelial dysplasia (87.54%), and squamous cell carcinoma (95.26%). A positive correlation was observed between correct SOD and age (P = 0.0143) and experience (P = 0.0189) of the pathologist. The time taken for giving second opinion by the pathologists ranged from 81.98 ± 32.89 to 90.72 ± 38.88 min. Smartphone camera is a handy and efficient tool in capturing photomicrographs from the compound microscope. Transfer of such photomicrograph via WhatsApp is an effective and convenient approach in procuring second opinion on histopathological diagnosis of oral pathologies. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Single inhalation exposure to /sup 90/SrCl/sub 2/ in the beagle dog: late biological effects

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gillett, N.A.; Muggenburg, B.A.; Boecker, B.B.

1987-08-01

Late-occurring biologic effects were studied in beagle dogs that were given graded levels of /sup 90/SrCl/sub 2/ via single brief inhalation exposures and were subsequently observed for their life-span. Due to the soluble chemical form of the aerosol, /sup 90/Sr was rapidly translocated from lung and deposited in bone where it was subsequently retained for a long period of time. Radiation-induced lesions were confined to the bone, bone marrow, and adjacent soft tissue. Forty-five primary bone tumors occurred in 31 of 66 exposed dogs. Metastasis occurred from 21 tumors, with the lung being the most frequent site of metastasis (76%).more » Twenty-seven tumors were classified as different subtypes of osteosarcoma, 14 as hemangiosarcomas, 3 as fibrosarcomas, and 1 as a myxosarcoma. Four carcinomas arising from soft tissues adjacent to bone were also considered to be /sup 90/Sr induced. In contrast to bone tumors arising in beagles chronically exposed to 90Sr through ingestion, histologic lesions of radiation osteodystrophy were minimal in this study, indicating that these lesions are not a necessary precursor of osteosarcoma development. The incidences of hemangiosarcomas (31%) and telangiectatic osteosarcomas (11%) in addition to osteosarcomas suggest that the cell of origin for all of these neoplasms is a multipotent mesenchymal cell with the potential for various morphologic expressions dependent on local environmental factors.« less

A serine/threonine kinase, Cot/Tpl2, modulates bacterial DNA-induced IL-12 production and Th cell differentiation.

PubMed

Sugimoto, Kenji; Ohata, Mutsuhiro; Miyoshi, Jun; Ishizaki, Hiroyoshi; Tsuboi, Naotake; Masuda, Akio; Yoshikai, Yasunobu; Takamoto, Masaya; Sugane, Kazuo; Matsuo, Seiichi; Shimada, Yasuhiro; Matsuguchi, Tetsuya

2004-09-01

A serine/threonine protein kinase, Cot/Tpl2, is indispensable for extracellular signal-regulated kinase (ERK) activation and production of TNF-alpha and PGE2 in LPS-stimulated macrophages. We show here that Cot/Tpl2 is also activated by other Toll-like receptor (TLR) ligands. Bacterial DNA rich in the dinucleotide CG (CpG-DNA), unlike LPS or synthetic lipopeptide, activated ERK in a Cot/Tpl2-independent manner. Peritoneal macrophages and bone marrow-derived DCs from Cot/Tpl2-/- mice produced significantly more IL-12 in response to CpG-DNA than those from WT mice. Enhanced IL-12 production in Cot/Tpl2-/- macrophages is, at least partly, regulated at the transcriptional level, and the elevated IL-12 mRNA level in Cot/Tpl2-/- macrophages is accompanied by decreased amounts of IL-12 repressors, such as c-musculoaponeurotic fibrosarcoma (c-Maf) and GATA sequence in the IL-12 promoter-binding protein (GA-12-binding protein; GAP-12) in the nucleus. Consistently, Cot/Tpl2-/- mice showed Th1-skewed antigen-specific immune responses upon OVA immunization and Leishmania major infection in vivo. These results indicate that Cot/Tpl2 is an important negative regulator of Th1-type adaptive immunity, that it achieves this regulation by inhibiting IL-12 production from accessory cells, and that it might be a potential target molecule in CpG-DNA-guided vaccination.

Modulation of in vivo distribution through chelator: Synthesis and evaluation of a 2-nitroimidazole-dipicolylamine-(99m)Tc(CO)3 complex for detecting tumor hypoxia.

PubMed

Mallia, Madhava B; Mittal, Sweety; Sarma, Haladhar D; Banerjee, Sharmila

2016-01-01

Previous studies have clearly demonstrated strong correlation between in vivo distribution and blood clearance of radiopharmaceuticals for the detection of hypoxia. Present study describes an attempt to improve the in vivo distribution of a previously reported 2-nitroimidazole-(99m)Tc(CO)3 complex by tuning its blood clearance pattern through structural modification of the ligand. Herein, a 2-nitroimidazole-dipicolylamine ligand (2-nitroimidazole-DPA) was synthesized in a two-step procedure and radiolabeled with (99m)Tc(CO)3 core. Subsequently, the complex was evaluated in Swiss mice bearing fibrosarcoma tumor. As intended by its design, 2-nitroimidazole-DPA-(99m)Tc(CO)3 complex was more lipophilic than previously reported 2-nitroimidazole-DETA-(99m)Tc(CO)3 complex (DETA-diethylenetriamine) and showed slower blood clearance. Consequently it showed higher tumor uptake than 2-nitroimidazole-DETA-(99m)Tc(CO)3 complex. Significantly, despite structural modifications, other parameters such as the tumor to blood ratio and tumor to muscle ratio of the 2-nitroimidazole-DPA-(99m)Tc(CO)3 complex remained comparable to that of 2-nitroimidazole-DETA-(99m)Tc(CO)3 complex. Present study demonstrates the feasibility of structural modifications for improving in vivo tumor uptake of hypoxia detecting radiopharmaceuticals. This might encourage researchers to improve suboptimal properties of a potential radiopharmaceuticals rather than ignoring it altogether. Copyright © 2015 Elsevier Ltd. All rights reserved.

Singlet oxygen explicit dosimetry to predict local tumor control for HPPH-mediated photodynamic therapy

NASA Astrophysics Data System (ADS)

Penjweini, Rozhin; Kim, Michele M.; Ong, Yi Hong; Zhu, Timothy C.

2017-02-01

This preclinical study examines four dosimetric quantities (light fluence, photosensitizer photobleaching ratio, PDT dose, and reacted singlet oxygen ([1O2]rx)) to predict local control rate (LCR) for 2-(1-Hexyloxyethyl)-2-devinyl pyropheophorbide (HPPH)-mediated photodynamic therapy (PDT). Mice bearing radiation-induced fibrosarcoma (RIF) tumors were treated with different in-air fluences (135, 250 and 350 J/cm2) and in-air fluence rates (50, 75 and 150 mW/cm2) at 0.25 mg/kg HPPH and a drug-light interval of 24 hours using a 1 cm diameter collimated laser beam at 665 nm wavelength. A macroscopic model was used to calculate ([1O2]rx)) based on in vivo explicit dosimetry of the initial tissue oxygenation, photosensitizer concentration, and tissue optical properties. PDT dose was defined as a temporal integral of drug concentration and fluence rate (φ) at a 3 mm tumor depth. Light fluence rate was calculated throughout the treatment volume based on Monte-Carlo simulation and measured tissue optical properties. The tumor volume of each mouse was tracked for 30 days after PDT and Kaplan-Meier analyses for LCR were performed based on a tumor volume <=100 mm3, for four dose metrics: fluence, HPPH photobleaching rate, PDT dose, and ([1O2]rx)). The results of this study showed that ([1O2]rx)) is the best dosimetric quantity that can predict tumor response and correlate with LCR.

Modification of radiation carcinogenesis by marihuana

DOE Office of Scientific and Technical Information (OSTI.GOV)

Montour, J.L.; Dutz, W.; Harris, L.S.

1981-03-15

Male, female, and ovariectomized female Sprague-Dawley rats were irradiated with 400 rads, 150 rads, or 300 rads, respectively, of /sup 60/Co gamma rays when they were between 40 and 50 days of age. The animals were injected three times weekly with either marihuana extract or with alcohol-emulphor carrier. Comparable unirradiated groups were similarly injected. Mean survival time in males was significantly shorter in the 400 rad + marihuana group compared with the three other groups whose mean survival times did not differ. Through the 546 days that the males were observed, the total number of tumors other than fibrosarcomas wasmore » significantly greater following radiation and marihuana (22) than radiation alone (6). Fifteen of the tumors were of breast or endocrine tissues. No differences were seen in the unirradiated groups. In the females, which were observed for 635 days, the total number of breast tumors was greater with the combined treatment (38) compared with radiation alone (22). This was entirely due to a marked difference in the adenocarcinoma incidence, which was 21 (radiation + marihuana) compared with four (radiation alone). The number of adenofibromas was similar in the two groups. In the unirradiated female groups the breast adenocarcinoma incidence was eight in the marihuana group and two in the control group. Ovariectomy resulted in a lower breast tumor incidence in all groups. Nonbreast tumors were more frequent in the ovariectomized-irradiated groups. Radiation plus marihuana produced more nonbreast tumors (25) than radiation alone (17) in the ovariectomized females.« less

Feline dry eye syndrome of presumed neurogenic origin: a case report.

PubMed

Sebbag, Lionel; Pesavento, Patricia A; Carrasco, Sebastian E; Reilly, Christopher M; Maggs, David J

2018-01-01

A 14-year-old female spayed Abyssinian cat, which about 1 year previously underwent thoracic limb amputation, radiotherapy and chemotherapy for an incompletely excised vaccine-related fibrosarcoma, was presented for evaluation of corneal opacity in the left eye (OS). The ocular surface of both eyes (OU) had a lackluster appearance and there was a stromal corneal ulcer OS. Results of corneal aesthesiometry, Schirmer tear test-1 (STT-1) and tear film breakup time revealed corneal hypoesthesia, and quantitative and qualitative tear film deficiency OU. Noxious olfactory stimulation caused increased lacrimation relative to standard STT-1 values suggesting an intact nasolacrimal reflex. Various lacrimostimulants were administered in succession; namely, 1% pilocarpine administered topically (15 days) or orally (19 days), and topically applied 0.03% tacrolimus (47 days). Pilocarpine, especially when given orally, was associated with notable increases in STT-1 values, but corneal ulceration remained/recurred regardless of administration route, and oral pilocarpine resulted in gastrointestinal upset. Tacrolimus was not effective. After 93 days, the cat became weak and lame and a low thyroxine concentration was detected in serum. The cat was euthanized and a necropsy performed. Both lacrimal glands were histologically normal, but chronic neutrophilic keratitis and reduced conjunctival goblet cell density were noted OU. The final diagnosis was dry eye syndrome (DES) of presumed neurogenic origin, associated with corneal hypoesthesia. This report reinforces the importance of conducting tearfilm testing in cats with ocular surface disease, as clinical signs of DES were different from those described in dogs.

Inhibitory effect of blue light emitting diode on migration and invasion of cancer cells.

PubMed

Oh, Phil-Sun; Kim, Hyun-Soo; Kim, Eun-Mi; Hwang, Hyosook; Ryu, Hyang Hwa; Lim, SeokTae; Sohn, Myung-Hee; Jeong, Hwan-Jeong

2017-12-01

The aim of this study was to determine the effects and molecular mechanism of blue light emitting diode (LED) in tumor cells. A migration and invasion assay for the metastatic behavior of mouse colon cancer CT-26 and human fibrosarcoma HT-1080 cells was performed. Cancer cell migration-related proteins were identified by obtaining a 2-dimensional gel electrophoresis (2-DE) in total cellular protein profile of blue LED-irradiated cancer cells, followed by matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) analysis of proteins. Protein levels were examined by immunoblotting. Irradiation with blue LED inhibited CT-26 and HT-1080 cell migration and invasion. The anti-metastatic effects of blue LED irradiation were associated with inhibition of matrix metalloproteinase (MMP)-2 and MMP-9 expression. P38 MAPK phosphorylation was increased in blue LED-irradiated CT-26 and HT-1080 cells, but was inhibited after pretreatment with SB203580, a specific inhibitor of p38 MAPK. Inhibition of p38 MAPK phosphorylation by SB203580 treatment increased number of migratory cancer cells in CT-26 and HT-1080 cells, indicating that blue LED irradiation inhibited cancer cell migration via phosphorylation of p38 MAPK. Additionally blue LED irradiation of mice injected with CT-26 cells expressing luciferase decreased early stage lung metastasis compared to untreated control mice. These results indicate that blue LED irradiation inhibits cancer cell migration and invasion in vitro and in vivo. © 2017 Wiley Periodicals, Inc.

Quantitative phosphoproteomic analysis of RIP3-dependent protein phosphorylation in the course of TNF-induced necroptosis.

PubMed

Zhong, Chuan-Qi; Li, Yuanyue; Yang, Daowei; Zhang, Na; Xu, Xiaozheng; Wu, Yaying; Chen, Jinan; Han, Jiahuai

2014-03-01

Tumor necrosis factor (TNF) induced cell death in murine fibrosarcoma L929 cells is a model system in studying programed necrosis (also known as necroptosis). Receptor interacting protein 3 (RIP3), a serine-threonine kinase, is known to play an essential role in TNF-induced necroptosis; however, the phosphorylation events initiated by RIP3 activation in necroptotic process is still largely unknown. Here, we performed a quantitative MS based analysis to compare TNF-induced changes in the global phosphoproteome of wild-type (RIP3(+/+) ) and RIP3-knockdown L929 cells at different time points after TNF treatment. A total of 8058 phosphopeptides spanning 6892 phosphorylation sites in 2762 proteins were identified in the three experiments, in which cells were treated with TNF for 0.5, 2, and 4 h. By comparing the phosphorylation sites in wild-type and RIP3-knockdown L929 cells, 174, 167, and 177 distinct phosphorylation sites were revealed to be dependent on RIP3 at the 0.5, 2, and 4 h time points after TNF treatment, respectively. Notably, most of them were not detected in a previous phosphoproteomic analysis of RIP3-dependent phosphorylation in lipopolysaccharide-stimulated peritoneal macrophages and TNF-treated murine embryonic fibroblasts (MEFs), suggesting that the data presented in this report are highly relevant to the study of TNF-induced necroptosis of L929 cells. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Modification of radiation carcinogenesis by marijuana

DOE Office of Scientific and Technical Information (OSTI.GOV)

Montour, J.L.; Dutz, W.; Harris, L.S.

Male, female, and ovariectomized female Sprague-Dawley rats were irradiated with 400 rads, 150 rads, or 300 rads, respectively, of /sup 60/Co gamma rays when they were between 40 and 50 days of age. The animals were injected three times weekly with either marihuana extract or with alcohol-emulphor carrier. Comparable unirradiated groups were similarly injected. Mean survival time in males was significantly shorter in the 400 rad + marihuana group compared with the three other groups whose mean survival times did not differ. Through the 546 days that the males were observed, the total number of tumors other than fibrosarcomas wasmore » significantly greater following radiation and marihuana (22) than radiation alone (6). Fifteen of the tumors were of breast or endocrine tissues. No differences were seen in the unirradiated groups. In the females, which were observed for 635 days, the total number of breast tumors was greater with the combined treatment (38) compared with radiation alone (22). This was entirely due to a marked difference in the adenocarcinoma incidence, which was 21 (radiation + marihuana) compared with four (radiation alone). The number of adenofibromas was similar in the two groups. In the unirradiated female groups the breast adenocarcinoma incidence was eight in the marihuana group and two in the control group. Ovariectomy resulted in a lower breast tumor incidence in all groups. Nonbreast tumors were more frequent in the ovariectomized-irradiated groups. Radiation plus marihuana produced more nonbreast tumors (25) than radiation alone (17) in the ovariectomized females.« less

Enhanced cytostatic activity of the sesquiterpene lactone eupatoriopicrin by glutathione depletion.

PubMed Central

Woerdenbag, H. J.; Lemstra, W.; Malingré, T. M.; Konings, A. W.

1989-01-01

Eupatoriopicrin (EUP), a sesquiterpene lactone from Eupatorium cannabinum L., possesses cytostatic activity. This was demonstrated for FIO 26 cells in vitro with the aid of a clonogenic assay and in vivo by tumour growth delay in FIO 26 and Lewis lung tumour-bearing mice. In vitro the IC50 for 1 h exposure to EUP was 1.5 microgram ml-1 (4.1 nmol ml-1). This concentration depleted about 25% of its cellular GSH concentration. Pretreatment of FIO 26 cells with BSO, resulting in greater than 99%. GSH depletion, enhanced the cytotoxic effect of EUP. The dose-enhancement factor at the level of 10% cell survival was 2.3. Growth inhibition of the Lewis lung carcinoma and the FIO 26 fibrosarcoma, solidly growing in C57Bl mice, was found after i.v. injection of 20 or 40 mg kg-1 EUP, at a tumour volume of about 500 microliters. Pretreatment with BSO at a dose of 4 mmol kg-1 i.p., 6 h before EUP administration, resulted in a significantly stronger growth delay of both tumours compared with EUP only. At the time of EUP treatment, cellular GSH in the tumours was reduced by BSO treatment to about 60%. It is concluded that EUP possesses antitumour activity in vivo and that chemosensitisation of EUP may be accomplished by pretreatment with BSO, indicating that endogenous GSH protects against the cytostatic action of EUP. PMID:2757925

Vemurafenib skin phototoxicity is indirectly linked to ultraviolet A minimal erythema dose decrease.

PubMed

Brugière, C; Stefan, A; Morice, C; Cornet, E; Moreau, A; Allouche, S; Verneuil, L

2014-12-01

Vemurafenib, an anti-rapidly accelerated fibrosarcoma kinase B (BRAF) molecule, improves survival among patients with metastatic BRAF-mutated melanoma. Photosensitivity, a frequent cutaneous adverse effect induced by vemurafenib, can lead to cessation of treatment. To investigate photosensitivity mechanisms in patients treated with vemurafenib for metastatic melanoma. In a prospective study of 12 patients, photobiological explorations with measurements of ultraviolet A (UVA) minimal erythema dose (MED) and polychromatic MED were performed over 3 days in all 12 patients. UVA MED and polychromatic MED were also assessed for four patients before treatment. We then performed spectrophotometric analyses of (i) serum and faeces in these four patients, before and after introduction of vemurafenib; (ii) the lyophilized form of vemurafenib without excipient added; and (iii) the lyophilized form of vemurafenib added to serum and faeces before treatment. Photosensitivity was present in 92% of the patients. UVA MED was normal before treatment and decreased after treatment, while polychromatic MED remained normal. The same three peaks (210, 260 and 310 nm) were identified in the spectrum for UVB and UVC but not for UVA on spectrophotometric analyses for each condition (lyophilized vemurafenib; serum and faeces after introduction of vemurafenib; and lyophilized vemurafenib added to serum and faeces before treatment). The peaks were different before treatment. Our study confirms that photosensitivity under vemurafenib treatment was a UVA phototoxicity reaction, and our results suggest that a metabolite of vemurafenib rather than the parent molecule is involved in this phototoxicity. © 2014 British Association of Dermatologists.

Vascular infarction by subcutaneous application of tissue factor targeted to tumor vessels with NGR-peptides: activity and toxicity profile.

PubMed

Dreischalück, Johannes; Schwöppe, Christian; Spieker, Tilmann; Kessler, Torsten; Tiemann, Klaus; Liersch, Ruediger; Schliemann, Christoph; Kreuter, Michael; Kolkmeyer, Astrid; Hintelmann, Heike; Mesters, Rolf M; Berdel, Wolfgang E

2010-12-01

tTF-NGR consists of the extracellular domain of the (truncated) tissue factor (tTF), a central molecule for coagulation in vivo, and the peptide GNGRAHA (NGR), a ligand of the surface protein aminopeptidase N (CD13). After deamidation of the NGR-peptide moiety, the fusion protein is also a ligand for integrin αvβ3 (CD51/CD61). Both surface proteins are upregulated on endothelial cells of tumor vessels. tTF-NGR showed binding to specific binding sites on endothelial cells in vitro as shown by flow cytometry. Subcutaneous injection of tTF-NGR into athymic mice bearing human HT1080 fibrosarcoma tumors induced tumor growth retardation and delay. Contrast enhanced ultrasound detected a decrease in tumor blood flow in vivo after application of tTF-NGR. Histological analysis of the tumors revealed vascular disruption due to blood pooling and thrombotic occlusion of tumor vessels. Furthermore, a lack of resistance was shown by re-exposure of tumor-bearing mice to tTF-NGR after regrowth following a first cycle of treatment. However, after subcutaneous (s.c.) push injection with therapeutic doses (1-5 mg/kg bw) side effects have been observed, such as skin bleeding and reduced performance. Since lethality started within the therapeutic dose range (LD10 approximately 2 mg/kg bw) no safe therapeutic window could be found. Limiting toxicity was represented by thrombo-embolic events in major organ systems as demonstrated by histology. Thus, subcutaneous injection of tTF-NGR represents an active, but toxic application procedure and compares unfavourably to intravenous infusion.

Amelioration of skewed Th1/Th2 balance in tumor-bearing and asthma-induced mice by oral administration of Agaricus blazei extracts.

PubMed

Takimoto, Hiroaki; Kato, Hanano; Kaneko, Masahiro; Kumazawa, Yoshio

2008-01-01

We showed in a previous study that hot-water extracts of Agaricus blazei (Agaricus extracts) had anti-tumor activity to Meth A fibrosarcoma, but it remains unclear whether the Agaricus extracts ameliorate the skewed balance of type-1 T helper (Th1) and type-2 T helper (Th2) cells. We examined whether Agaricus extracts effect the skewed Th1/Th2 balance in tumor-bearing and asthma-induced mice. When Meth A-bearing mice were given orally either Agaricus extracts or water once a day starting 5 days after tumor implantation, spleen T cells, prepared from tumor-bearing mice treated with Agaricus extracts, in response to anti-CD3 monoclonal antibody produced significantly higher levels of interferon gamma (IFN-gamma) than that of controls. The mRNA expression of IFN-gamma-inducing protein 10 and the frequency of CD69(+) or CD49d(+) cells, among activated T cells infiltrated into tumors, significantly increased in Agaricus-treated mice, compared with those of tumor-controls. In asthma-induced mice, treatment with the Agaricus extracts caused significant downregulation of OVA-specific antibody responses of IgG1 and IgE but not of IgG2a, and significantly decreased total cell numbers, levels of interleukin 5, and eosinophil numbers in bronchial alveolar lavage fluids. IFN-gamma production by anti-CD3-stimulated spleen cells, obtained from Agaricus-treated mice, significantly increased. Our results strongly suggest that oral administration of Agaricus extracts ameliorates the Th1/Th2 balance from the Th2-skewed conditions.

Evaluation of the 2-(1-Hexyloxyethyl)-2-devinyl pyropheophorbide (HPPH) mediated photodynamic therapy by macroscopic singlet oxygen modeling.

PubMed

Penjweini, Rozhin; Kim, Michele M; Liu, Baochang; Zhu, Timothy C

2016-12-01

Photodynamic therapy (PDT) is known as a non-invasive treatment modality that is based on photochemical reactions between oxygen, photosensitizer, and a special wavelength of light. However, a dosimetric predictor for PDT outcome is still elusive because current dosimetric quantities do not account for the differences in the PDT oxygen consumption rate for different fluence rates. In this study, we evaluate several dose metrics, total fluence, photobleaching ratio, PDT dose, and mean reacted singlet oxygen (mean [ 1 O 2 ] rx ) for predicting the PDT outcome and a clinically relevant tumor re-growth endpoint. For this reason, radiation-induced fibrosarcoma (RIF) mice tumors are treated with 2-(1-Hexyloxyethyl)-2-devinyl pyropheophorbide (HPPH) and different in-air fluences (30 J/cm 2 , 50 J/cm 2 , 135 J/cm 2 , 250 J/cm 2 , and 350 J/cm 2 ) and in-air fluence rates (20, 50, 75, 150 mW/cm 2 ). Explicit measurements of HPPH and oxygen concentration as well as tissue optical properties are performed pre- and post-treatment. Then, this information is incorporated into a macroscopic model to calculate the photobleaching, PDT dose, and mean [ 1 O 2 ] rx . Changes in tumor volume are tracked following the treatment and compared with the dose metrics. The correlation demonstrates that mean [ 1 O 2 ] rx  serves as a better dosimetric quantity for predicting treatment outcome and a clinically relevant tumor re-growth endpoint. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Effect of a topical vasodilator on tumor hypoxia and tumor oxygen guided radiotherapy using EPR oximetry.

PubMed

Hou, Huagang; Abramovic, Zrinka; Lariviere, Jean P; Sentjurc, Marjeta; Swartz, Harold; Khan, Nadeem

2010-05-01

We sought to reduce tumor hypoxia by topical application of a vasodilator, benzyl nicotinate (BN), and investigated its effect on the growth of tumors irradiated at times when tumor pO(2) increased. EPR oximetry was used to follow the changes in the tissue pO(2) of subcutaneous radiation-induced fibrosarcoma (RIF-1) tumors during topical applications of 1.25-8% BN formulations for 5 consecutive days. The RIF-1 tumors were hypoxic with a tissue pO(2) of 4.6-7.0 mmHg. A significant increase in tumor pO(2) occurred 10-30 min after BN application. The formulation with the minimal BN concentration that produced a significant increase in tumor pO(2) was used for the radiation study. The tumors were irradiated (4 Gy x 5) at the time of the maximum increase in pO(2) observed with the 2.5% BN formulation. The tumors with an increase in pO(2) of greater than 2 mmHg from the baseline after application of BN on day 1 had a significant growth inhibition compared to the tumors with an increase in pO(2) of less than 2 mmHg. The results indicate that the irradiation of tumors at the time of an increase in pO(2) after the topical application of the 2.5% BN formulation led to a significant growth inhibition. EPR oximetry provided dynamic information on the changes in tumor pO(2), which could be used to identify responders and non-responders and schedule therapy during the experiments.

Color-coded Live Imaging of Heterokaryon Formation and Nuclear Fusion of Hybridizing Cancer Cells.

PubMed

Suetsugu, Atsushi; Matsumoto, Takuro; Hasegawa, Kosuke; Nakamura, Miki; Kunisada, Takahiro; Shimizu, Masahito; Saji, Shigetoyo; Moriwaki, Hisataka; Bouvet, Michael; Hoffman, Robert M

2016-08-01

Fusion of cancer cells has been studied for over half a century. However, the steps involved after initial fusion between cells, such as heterokaryon formation and nuclear fusion, have been difficult to observe in real time. In order to be able to visualize these steps, we have established cancer-cell sublines from the human HT-1080 fibrosarcoma, one expressing green fluorescent protein (GFP) linked to histone H2B in the nucleus and a red fluorescent protein (RFP) in the cytoplasm and the other subline expressing RFP in the nucleus (mCherry) linked to histone H2B and GFP in the cytoplasm. The two reciprocal color-coded sublines of HT-1080 cells were fused using the Sendai virus. The fused cells were cultured on plastic and observed using an Olympus FV1000 confocal microscope. Multi-nucleate (heterokaryotic) cancer cells, in addition to hybrid cancer cells with single-or multiple-fused nuclei, including fused mitotic nuclei, were observed among the fused cells. Heterokaryons with red, green, orange and yellow nuclei were observed by confocal imaging, even in single hybrid cells. The orange and yellow nuclei indicate nuclear fusion. Red and green nuclei remained unfused. Cell fusion with heterokaryon formation and subsequent nuclear fusion resulting in hybridization may be an important natural phenomenon between cancer cells that may make them more malignant. The ability to image the complex processes following cell fusion using reciprocal color-coded cancer cells will allow greater understanding of the genetic basis of malignancy. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Monitoring PDT effects in murine tumors by spectroscopic and imaging techniques

NASA Astrophysics Data System (ADS)

Ramaprasad, Subbaraya; Rzepka, Elzbieta; Pi, Jiaxiong; Joshi, Shantaram S.; Dobhal, Mahabeer; Missert, Joseph; Pandey, Ravindra K.

2004-04-01

The changes in the tumor that occur following photodynamic therapy (PDT) were studied using a small animal MR imager operating at 7Tesla. The animal model used in these studies was mice bearing radiation induced fibrosarcoma (RIF) tumor on the foot dorsum. The mice were injected with 10μM/kg of one of the photosensitizers: (1) Photofrin, (2) Non-fluorinated porphyrin photosensitizer (DOD-1), (3) Fluorinated porphyrin photosensitizer (DOD-2) and, (4) Fluorinated chlorin photosensitizer (DOD-6). Laser light at 630 or 650 nm (150 mW/cm2, 270 joules/cm2) was delivered to the tumor at 2-24 hours of photosensitizer administration. The MR spectroscopic and imaging examination of the tumors involved both the 1H and 31P nuclei. The tumor bioenergetics was measured by 31P spectroscopy. The water proton relaxivity and diffusion measurements were used to obtain local changes in different regions of the tumor. Changes in 31P MR spectra were observed following PDT using Photofrin and fluorinated chlorin sensitizer (DOD-6). However, no significant changes were observed when the fluorinated porphyrin and its nonfluorinated analog were used. The PDT induced changes in tumor volumes showed significant tumor regression with Photofrin, fluorinated porphyrin and chlorin sensitizers. No tumor regression was observed with the non labeled porphyrin sensitizer and the growth profile followed the general pattern of unperturbed tumors. Serial noninvasive measurements of tumor response to PDT are measurable by both MRI and MRS. The MR derived parameters that are characteristic of the tumor status before and after the therapy are discussed here.

Collagen gel protects L929 cells from TNFα-induced death by activating NF-κB.

PubMed

Wang, Hong-Ju; Li, Meng-Qi; Liu, Wei-Wei; Hayashi, Toshihiko; Fujisaki, Hitomi; Hattori, Shunji; Tashiro, Shin-Ichi; Onodera, Satoshi; Ikejima, Takashi

2017-09-01

Type I collagen is one of the most abundant components of extracellular matrix. We previously illustrated that murine fibrosarcoma L929 cells grew well on type I collagen gel and escaped from TNFα-induced cell death. In this study, we investigated the mechanism underlying the protective effect of collagen gel. We used western blot, confocal microscopy, MTT assay and flow cytometry by introducing fluorescence staining to determine the expression levels of nuclear factor kappa B (NF-κB), inhibitory ratio and autophagy. L929 cells on collagen gel showed higher expression of NF-κB in the nucleus. Inhibition of NF-κB with pyrrolidine dithiocarbamate hydrochloride (PDTC) or knockdown by NF-κB-siRNA canceled the protective effect of collagen gel on L929 cells from TNFα-induced death, suggesting for the role of NF-κB in the protection from cell death. We found a new aspect of the effect of PDTC on L929 cells cultured on collagen gel. PDTC alone without TNFα induced apoptosis in the L929 cells cultured on collagen gel but not the cells on plastic dish. The apoptosis induction of the L929 cells cultured on collagen gel with PDTC was repressed by inhibiting autophagy with chloroquine, an autophagy inhibitor, suggesting that autophagy contributes to the death induced by the treatment with PDTC. Possible underlying mechanism of this finding is discussed. NF-κB played an important role in protecting the L929 cells cultured on collagen gel from TNFα-induced death.

Tumor-evoked hyperalgesia and sensitization of nociceptive dorsal horn neurons in a murine model of cancer pain

PubMed Central

Khasabov, Sergey G.; Hamamoto, Darryl T.; Harding-Rose, Catherine; Simone, Donald A.

2009-01-01

Pain associated with cancer, particularly when tumors metastasize to bone, is often severe and debilitating. Better understanding of the neurobiological mechanisms underlying cancer pain will likely lead to the development of more effective treatments. The aim of this study was to characterize changes in response properties of nociceptive dorsal horn neurons following implantation of fibrosarcoma cells into and around the calcaneus bone, an established model of cancer pain. Extracellular electrophysiological recordings were made from wide dynamic range (WDR) and high threshold (HT) dorsal horn neurons in mice with tumor-evoked hyperalgesia and control mice. WDR and HT neurons were examined for ongoing activity and responses to mechanical, heat, and cold stimuli applied to the plantar surface of the hind paw. Behavioral experiments showed that mice exhibited hyperalgesia to mechanical and heat stimuli applied to their tumor-bearing hind paw. WDR, but not HT, nociceptive dorsal horn neurons in tumor-bearing mice exhibited sensitization to mechanical, heat, and cold stimuli and may contribute to tumor-evoked hyperalgesia. Specifically, the proportion of WDR neurons that exhibited ongoing activity and their evoked discharge rates were greater in tumor-bearing than in control mice. In addition, WDR neurons exhibited lower response thresholds for mechanical and heat stimuli, and increased responses to suprathreshold mechanical, heat, and cold stimuli. Our findings show that sensitization of WDR neurons contribute to cancer pain and support the notion that the mechanisms underlying cancer pain differ from those that contribute to inflammatory and neuropathic pain. PMID:17935703

Fine needle aspiration cytology in lesions of the nose, nasal cavity and paranasal sinuses.

PubMed

Gupta, Nalini; Kaur, Jasleen; Srinivasan, Radhika; Das, Ashim; Mohindra, Satyawati; Rajwanshi, Arvind; Nijhawan, Raje

2011-01-01

To assess the spectrum of lesions in the sinonasal region diagnosed on FNAC. This is a retrospective audit of sinonasal lesions diagnosed on FNAC over a period of 12 years (1998-2009). Out of a total of 79,851 FNACs, 158 (0.2%) were from the sinonasal region. FNAC was non-diagnostic in 20 (12.6%) cases. Infective/inflammatory lesions comprised of 30 (19%) cases including non-specific inflammation (19), fungal infection (7), tuberculosis (2), actinomycosis (1) and filariasis (1). Benign cysts (24; 15.2%) included epidermal inclusion cysts, mucocele and aneurysmal bone cyst. Benign bone tumors (4) comprised of giant cell tumor, fibrous dysplasia, chondroma, and osteoblastoma. Other benign tumors included lipoma (6), hemangioma (5), schwannoma (2), meningioma (1), pleomorphic adenoma (1), sebaceous adenoma (1) and other skin adnexal tumors (3). Malignant epithelial tumors (24; 15.2%) included squamous cell carcinoma (10), basal cell carcinoma (5), poorly differentiated carcinoma (4) and metastatic carcinoma (5). Two cases of chordoma and one case each of dermatofibrosarcoma pertuberance and hemangiopericytoma were seen. Sarcomas included sarcoma, not otherwise specified (4), rhabdomyosarcoma (3), osteosarcoma (2), chondrosarcoma (2), leiomyosarcoma (1), malignant fibrous histiocytoma (1), fibrosarcoma (1) and malignant peripheral nerve sheath tumor (1). There were cases of malignant small round cell tumor (11), non-Hodgkin lymphoma (3), plasmacytoma (2) and malignant melanoma (2). A variety of non-neoplastic and neoplastic conditions can involve the sinonasal region. FNAC is a reliable diagnostic procedure in a good number of cases, especially in the light of clinico-radiological data. Copyright © 2011 S. Karger AG, Basel.

Induction of nasal and nasopharyngeal tumours in Sprague-Dawley rats fed with Chinese salted fish.

PubMed

Zheng, X; Luo, Y; Christensson, B; Drettner, B

1994-01-01

Epidemiological studies have implied that Chinese salted fish is a human nasopharyngeal carcinogen. In the present study, 162 Sprague-Dawley rats were randomly assigned to one of four experimental groups. Rats in groups 1 (n = 41) and 3 (n = 40) were exposed to salted fish from birth through the breast feeding period by giving the maternal rats a diet containing 10% and 5% salted fish, respectively, later feeding the rats with pellets containing 10% and 5% of salted fish respectively. In group 2, the rats (n = 41) were given pellets containing 10% of salted fish from 6 weeks of age. Rats in group 4 (n = 40), serving as controls, were only given ordinary pellets. Three rats had nasopharyngeal tumours, 2 from group 1 had a poorly differentiated carcinoma and a squamous cell carcinoma. One rat from group 2 had a squamous cell carcinoma. Four rats had nasal tumours, one fibrosarcoma and one adenocarcinoma were found in rats from group 1. One rhabdomyosarcoma was found in group 2, and one soft tissue sarcoma was found in a rat in group 3. No nasal or nasopharyngeal tumours appeared in the control group. The difference in the occurrence of malignant nasal and nasopharyngeal tumours among the four experimental groups was statistically significant (one tailed p for trend = 0.041). The frequency of tumours appearing in other organs such as the breast, kidney, lung, liver and brain was not significantly different between the salted fish treated groups and the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Survival times for canine intranasal sarcomas treated with radiation therapy: 86 cases (1996-2011).

PubMed

Sones, Evan; Smith, Annette; Schleis, Stephanie; Brawner, William; Almond, Gregory; Taylor, Kathryn; Haney, Siobhan; Wypij, Jackie; Keyerleber, Michele; Arthur, Jennifer; Hamilton, Terrance; Lawrence, Jessica; Gieger, Tracy; Sellon, Rance; Wright, Zack

2013-01-01

Sarcomas comprise approximately one-third of canine intranasal tumors, however few veterinary studies have described survival times of dogs with histologic subtypes of sarcomas separately from other intranasal tumors. One objective of this study was to describe median survival times for dogs treated with radiation therapy for intranasal sarcomas. A second objective was to compare survival times for dogs treated with three radiation therapy protocols: daily-fractionated radiation therapy; Monday, Wednesday, and Friday fractionated radiation therapy; and palliative radiation therapy. Medical records were retrospectively reviewed for dogs that had been treated with radiation therapy for confirmed intranasal sarcoma. A total of 86 dogs met inclusion criteria. Overall median survival time for included dogs was 444 days. Median survival time for dogs with chondrosarcoma (n = 42) was 463 days, fibrosarcoma (n = 12) 379 days, osteosarcoma (n = 6) 624 days, and undifferentiated sarcoma (n = 22) 344 days. Dogs treated with daily-fractionated radiation therapy protocols; Monday, Wednesday and Friday fractionated radiation therapy protocols; and palliative radiation therapy protocols had median survival times of 641, 347, and 305 days, respectively. A significant difference in survival time was found for dogs receiving curative intent radiation therapy vs. palliative radiation therapy (P = 0.032). A significant difference in survival time was also found for dogs receiving daily-fractionated radiation therapy vs. Monday, Wednesday and Friday fractionated radiation therapy (P = 0.0134). Findings from this study support the use of curative intent radiation therapy for dogs with intranasal sarcoma. Future prospective, randomized trials are needed for confirmation of treatment benefits. © 2012 Veterinary Radiology & Ultrasound.

Feline dry eye syndrome of presumed neurogenic origin: a case report

PubMed Central

Sebbag, Lionel; Pesavento, Patricia A; Carrasco, Sebastian E; Reilly, Christopher M; Maggs, David J

2018-01-01

Case summary A 14-year-old female spayed Abyssinian cat, which about 1 year previously underwent thoracic limb amputation, radiotherapy and chemotherapy for an incompletely excised vaccine-related fibrosarcoma, was presented for evaluation of corneal opacity in the left eye (OS). The ocular surface of both eyes (OU) had a lackluster appearance and there was a stromal corneal ulcer OS. Results of corneal aesthesiometry, Schirmer tear test-1 (STT-1) and tear film breakup time revealed corneal hypoesthesia, and quantitative and qualitative tear film deficiency OU. Noxious olfactory stimulation caused increased lacrimation relative to standard STT-1 values suggesting an intact nasolacrimal reflex. Various lacrimostimulants were administered in succession; namely, 1% pilocarpine administered topically (15 days) or orally (19 days), and topically applied 0.03% tacrolimus (47 days). Pilocarpine, especially when given orally, was associated with notable increases in STT-1 values, but corneal ulceration remained/recurred regardless of administration route, and oral pilocarpine resulted in gastrointestinal upset. Tacrolimus was not effective. After 93 days, the cat became weak and lame and a low thyroxine concentration was detected in serum. The cat was euthanized and a necropsy performed. Both lacrimal glands were histologically normal, but chronic neutrophilic keratitis and reduced conjunctival goblet cell density were noted OU. Relevance and novel information The final diagnosis was dry eye syndrome (DES) of presumed neurogenic origin, associated with corneal hypoesthesia. This report reinforces the importance of conducting tearfilm testing in cats with ocular surface disease, as clinical signs of DES were different from those described in dogs. PMID:29318025

Modified Gompertz equation for electrotherapy murine tumor growth kinetics: predictions and new hypotheses.

PubMed

Cabrales, Luis E Bergues; Nava, Juan J Godina; Aguilera, Andrés Ramírez; Joa, Javier A González; Ciria, Héctor M Camué; González, Maraelys Morales; Salas, Miriam Fariñas; Jarque, Manuel Verdecia; González, Tamara Rubio; Mateus, Miguel A O'Farril; Brooks, Soraida C Acosta; Palencia, Fabiola Suárez; Zamora, Lisset Ortiz; Quevedo, María C Céspedes; Seringe, Sarah Edward; Cuitié, Vladimir Crombet; Cabrales, Idelisa Bergues; González, Gustavo Sierra

2010-10-28

Electrotherapy effectiveness at different doses has been demonstrated in preclinical and clinical studies; however, several aspects that occur in the tumor growth kinetics before and after treatment have not yet been revealed. Mathematical modeling is a useful instrument that can reveal some of these aspects. The aim of this paper is to describe the complete growth kinetics of unperturbed and perturbed tumors through use of the modified Gompertz equation in order to generate useful insight into the mechanisms that underpin this devastating disease. The complete tumor growth kinetics for control and treated groups are obtained by interpolation and extrapolation methods with different time steps, using experimental data of fibrosarcoma Sa-37. In the modified Gompertz equation, a delay time is introduced to describe the tumor's natural history before treatment. Different graphical strategies are used in order to reveal new information in the complete kinetics of this tumor type. The first stage of complete tumor growth kinetics is highly non linear. The model, at this stage, shows different aspects that agree with those reported theoretically and experimentally. Tumor reversibility and the proportionality between regions before and after electrotherapy are demonstrated. In tumors that reach partial remission, two antagonistic post-treatment processes are induced, whereas in complete remission, two unknown antitumor mechanisms are induced. The modified Gompertz equation is likely to lead to insights within cancer research. Such insights hold promise for increasing our understanding of tumors as self-organizing systems and, the possible existence of phase transitions in tumor growth kinetics, which, in turn, may have significant impacts both on cancer research and on clinical practice.

Malignant mesothelioma induced by asbestos and zeolite in the mouse peritonenal cavity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Suzuki, Y.; Kohyama, N.

1984-10-01

The carcinogenicity of asbestos (amosite and chrysotile) and zeolite (fibrous erionite, mordenite, and synthetic zeolite 4A) were studied in the peritoneum of 586 BALB/C male mice after a single intraperitoneal or intraabdominal wall injection. Tumors developed in 93 of 394 animals (23.6%) treated with asbestos or fibrous erionite 7 months or more after administration. All of the induced peritoneal tumors were intimately associated with marked peritoneal fibrosis, in which asbestos or erionite fibers were regularly detected. Histopathologically, 83 of 93 were consistent with malignant mesotheliomas. Other tumors consisted of 6 plasmacytomas, 1 histiocytoma, 1 liposarcoma, 1 osteosarcoma, and 1 adenocarcinomamore » of the pancreas. Two of the cases of mesotheliomas were associated with plasmacytoma. In many instances, the primary site of the mesotheliomas seemed to be multiple, the favorite sites being the omentum, mesentery, serosae of the gastrointestinal and genital organs, the diaphragm, the capsule of the liver and spleen, and the abdominal wall peritoneum. In addition to the 93 peritoneal tumors, 3 extraperitoneal tumors (1 fibrosarcoma and 2 rhabdomyosarcomas) were induced by amosite which was probably accidentally injected into the extraperitoneal connective tissue and the striated muscle tissue of the abdominal wall, respectively. These three tumors were also intimately associated with focal fibrosis in which amosite fibers were detected. Among the three different types of zeolite, only fibrous erionite showed striking carcinogenicity and marked fibrogenicity. The erionite-induced mesotheliomas were similar to those induced by asbestos in exhibiting long latency, in gross appearance, in histology, and in close association with fibrosis.« less

A novel derivative of decursin, CSL-32, blocks migration and production of inflammatory mediators and modulates PI3K and NF-κB activities in HT1080 cells.

PubMed

Lee, Seung-Hee; Lee, Jee Hyun; Kim, Eun-Ju; Kim, Won-Jung; Suk, Kyoungho; Kim, Joo-Hwan; Song, Gyu Yong; Lee, Won-Ha

2012-07-01

Decursin and related coumarin compounds in herbal extracts have a number of biological activities against inflammation, angiogenesis and cancer. We have analysed a derivative of decursin (CSL-32) for activity against inflammatory activation of cancer cells, such as migration, invasion and expression of pro-inflammatory mediators. The human fibrosarcoma cell line, HT1080, was treated with TNFα (tumour necrosis factor α) in the presence or absence of CSL-32. The cellular responses and modification of signalling adapters were analysed with respect to the production of pro-inflammatory mediators, as also migration, adhesion and invasion. Treatment of HT1080 cells with CSL-32 inhibited their proliferation, without affecting cell viability, and TNFα-induced expression of pro-inflammatory mediators, such as MMP-9 (matrix metalloproteinase-9) and IL-8 (interleukin-8). CSL-32 also suppressed phosphorylation and degradation of IκB (inhibitory κB), phosphorylation of p65 subunit of NF-κB (nuclear factor-κB) and nuclear translocation of NF-κB, which are required for the expression of pro-inflammatory mediators. In addition, CSL-32 inhibited invasion and migration of HT1080 cells, as also cellular adhesion to fibronectin, an ECM (extracellular matrix) protein. CSL-32 treatment resulted in a dose-dependent inhibition of PI3K (phosphoinositide 3-kinase) activity, required for the cellular migration. The analyses show that CSL-32 inhibits processes associated with inflammation, such as the production of pro-inflammatory mediators, as well as adhesion, migration and invasion in HT1080 cells.

Erythropoiesis stimulating agents and techniques: a challenge for doping analysts.

PubMed

Jelkmann, W

2009-01-01

Recombinant human erythropoietin (rHuEPO) engineered in Chinese hamster ovary (CHO) cell cultures (Epoetin alfa and Epoetin beta) and its hyperglycosylated analogue Darbepoetin alfa are known to be misused by athletes. The drugs can be detected by isoelectric focusing (IEF) and immunoblotting of urine samples, because "EPO" is in reality a mixture of isoforms and the N-glycans of the recombinant products differ from those of the endogenous hormone. However, there is a plethora of novel erythropoiesis stimulating agents (ESAs). Since the originator Epoetins alfa and beta are no longer protected by patent in the European Union, rHuEPO biosimilars have entered the market. In addition, several companies in Asia, Africa and Latin America produce copied rHuEPOs for clinical purposes. While the amino acid sequence of all Epoetins is identical, the structure of their glycans differs depending on the mode of production. Some products contain more acidic and others more basic EPO isoforms. Epoetin delta is special, as it was engineered by homologous recombination in human fibrosarcoma cells (HT-1080), thus lacking N-glycolylneuraminic acid like native human EPO. ESAs under development include EPO fusion proteins, synthetic erythropoiesis stimulating protein (SEP) and peptidic (Hematide(), CNTO 528) as well as non-peptidic EPO mimetics. Furthermore, preclinical respectively clinical trials have been performed with small orally active drugs that stimulate endogenous EPO production by activating the EPO promoter ("GATA-inhibitors": diazepane derivatives) or enhancer ("HIF-stabilizers": 2-oxoglutarate analogues). The prohibited direct EPO gene transfer may become a problem in sports only in the future.

Protein-bound polysaccharide-K reduces the proportion of regulatory T cells in vitro and in vivo.

PubMed

Aoki, Rieko; Iijima, Hiroko; Kato, Mariko; Uchida, Motoyuki; Wada, Tsutomu; Murata, Masatsune; Ogawa, Kenji; Naritaka, Yoshihiko; Yoshimatsu, Kazuhiko

2014-01-01

Regulatory T cells (Tregs) play an important role in maintaining immunological tolerance. However, this mechanism is one of the major obstacles to overcome when attempting to improve antitumor immunity. Protein-bound polysaccharide‑K (PSK) has been used clinically as an antitumor drug, and one of its antitumor mechanisms involves improvement of the tumor-induced immunosuppressive state. Therefore, we investigated whether PSK affects Tregs in vitro and in vivo. In the in vitro study, CD4⁺CD25⁻ cells were separated from normal mouse spleen and cultured with or without PSK in the presence of TGF-β. Although TGF-β induced CD4⁺CD25⁺Foxp3⁺ Tregs, PSK reduced the proportion of TGF-β-induced Tregs. In the in vivo study, BALB/c mice were injected subcutaneously with methylcholanthrene-induced fibrosarcoma (Meth A) cells on day 0, and were administered PSK (50 mg/kg) intraperitoneally from day 1, three times per week. After 4 weeks, the tumor volume, the proportion of Tregs and the CD8+/Treg ratio in the spleen, plasma TGF-β concentration, and IFN-γ production by spleen cells were measured. PSK significantly reduced tumor growth, the proportion of Tregs in the spleen and the plasma TGF-β concentration, and significantly increased the CD8+/Treg ratio in the spleen and IFN-γ production by spleen cells. The reduction of the TGF-β concentration in blood by PSK appears to decrease the proportion of Tregs in lymphoid organs and to augment antitumor immunity.

Lung Inflammation, Injury, and Proliferative Response after Repetitive Particulate Hexavalent Chromium Exposure

PubMed Central

Beaver, Laura M.; Stemmy, Erik J.; Schwartz, Arnold M.; Damsker, Jesse M.; Constant, Stephanie L.; Ceryak, Susan M.; Patierno, Steven R.

2009-01-01

Background Chronic inflammation is implicated in the development of several human cancers, including lung cancer. Certain particulate hexavalent chromium [Cr(VI)] compounds are well-documented human respiratory carcinogens that release genotoxic soluble chromate and are associated with fibrosis, fibrosarcomas, adenocarcinomas, and squamous cell carcinomas of the lung. Despite this, little is known about the pathologic injury and immune responses after repetitive exposure to particulate chromates. Objectives In this study we investigated the lung injury, inflammation, proliferation, and survival signaling responses after repetitive exposure to particulate chromate. Methods BALB/c mice were repetitively treated with particulate basic zinc chromate or saline using an intranasal exposure regimen. We assessed lungs for Cr(VI)-induced changes by bronchoalveolar lavage, histologic examination, and immunohistochemistry. Results Single exposure to Cr(VI) resulted in inflammation of lung tissue that persists for up to 21 days. Repetitive Cr(VI) exposure induced a neutrophilic inflammatory airway response 24 hr after each treatment. Neutrophils were subsequently replaced by increasing numbers of macrophages by 5 days after treatment. Repetitive Cr(VI) exposure induced chronic peribronchial inflammation with alveolar and interstitial pneumonitis dominated by lymphocytes and macrophages. Moreover, chronic toxic mucosal injury was observed and accompanied by increased airway pro-matrix metalloprotease-9. Injury and inflammation correlated with airways becoming immunoreactive for phosphorylation of the survival signaling protein Akt and the proliferation marker Ki-67. We observed a reactive proliferative response in epithelial cells lining airways of chromate-exposed animals. Conclusions These data illustrate that repetitive exposure to particulate chromate induces chronic injury and an inflammatory microenvironment that may promote Cr(VI) carcinogenesis. PMID:20049209

Safety evaluation of a human chimeric monoclonal antibody that recognizes the extracellular loop domain of claudin-2.

PubMed

Hashimoto, Yosuke; Hata, Tomoyuki; Tada, Minoru; Iida, Manami; Watari, Akihiro; Okada, Yoshiaki; Doi, Takefumi; Kuniyasu, Hiroki; Yagi, Kiyohito; Kondoh, Masuo

2018-05-30

Claudin-2 (CLDN-2), a pore-forming tight junction protein with a tetra-transmembrane domain, is involved in carcinogenesis and the metastasis of some cancers. Although CLDN-2 is highly expressed in the tight junctions of the liver and kidney, whether CLDN-2 is a safe target for cancer therapy remains unknown. We recently generated a rat monoclonal antibody (mAb, clone 1A2) that recognizes the extracellular domains of human and mouse CLDN-2. Here, we investigated the safety of CLDN-2-targeted cancer therapy by using 1A2 as a model therapeutic antibody. Because most human therapeutic mAbs are IgG1 subtype that can induce antibody-dependent cellular cytotoxicity, we generated a human-rat chimeric IgG1 form of 1A2 (xi-1A2). xi-1A2 activated Fcγ receptor IIIa in the presence of CLDN-2-expressing cells, indicating that xi-1A2 likely exerts antibody-dependent cellular cytotoxicity. At 24 h after its intravenous injection, xi-1A2 was distributed into the liver, kidney, and tumor tissues of mice bearing CLDN-2-expressing fibrosarcoma cells. Treatment of the xenografted mice with xi-1A2 attenuated tumor growth without apparent adverse effects, such as changes in body weight and biochemical markers of liver and kidney injury. These results support xi-1A2 as the lead candidate mAb for safe CLDN-2-targeted cancer therapy. Copyright © 2018 Elsevier B.V. All rights reserved.

A Transcriptional Regulatory Role for the Membrane Type-1 Matrix Metalloproteinase in Carcinogen-Induced Inflammasome Gene Expression.

PubMed

Sheehy, Samuel; Annabi, Borhane

2017-01-01

Signal-transducing functions driven by the cytoplasmic domain of membrane type-1 matrix metalloproteinase (MT1-MMP) are believed to regulate many inflammation-associated cancer cell functions including migration, proliferation, and survival. Aside from upregulation of the inflammation biomarker cyclooxygenase-2 (COX-2) expression, MT1-MMP's role in relaying intracellular signals triggered by extracellular pro-inflammatory cues remains poorly understood. Here, we triggered inflammation in HT1080 fibrosarcoma cells with phorbol-12-myristate-13-acetate (PMA), an inducer of COX-2 and of MT1-MMP. To assess the global transcriptional regulatory role that MT1-MMP may exert on inflammation biomarkers, we combined gene array screens with a transient MT1-MMP gene silencing strategy. Expression of MT1-MMP was found to exert both stimulatory and repressive transcriptional control of several inflammasome-related biomarkers such as interleukin (IL)-1B, IL-6, IL-12A, and IL-33, as well as of transcription factors such as EGR1, ELK1, and ETS1/2 in PMA-treated cells. Among the signal-transducing pathways explored, the silencing of MT1-MMP prevented PMA from phosphorylating extracellular signal-regulated kinase, inhibitor of κB, and p105 nuclear factor κB (NF-κB) intermediates. We also found a signaling axis linking MT1-MMP to MMP-9 transcriptional regulation. Altogether, our data indicate a significant involvement of MT1-MMP in the transcriptional regulation of inflammatory biomarkers consolidating its contribution to signal transduction functions in addition to its classical hydrolytic activity.

Curcumin and Viscum album Extract Decrease Proliferation and Cell Viability of Soft-Tissue Sarcoma Cells: An In Vitro Analysis of Eight Cell Lines Using Real-Time Monitoring and Colorimetric Assays.

PubMed

Harati, K; Behr, B; Daigeler, A; Hirsch, T; Jacobsen, F; Renner, M; Harati, A; Wallner, C; Lehnhardt, M; Becerikli, M

2017-01-01

The cytostatic effects of the polyphenol curcumin and Viscum album extract (VAE) were assessed in soft-tissue sarcoma (STS) cells. Eight human STS cell lines were used: fibrosarcoma (HT1080), liposarcoma (SW872, T778, MLS-402), synovial sarcoma (SW982, SYO1, 1273), and malignant fibrous histiocytoma (U2197). Primary human fibroblasts served as control cells. Cell proliferation, viability, and cell index (CI) were analyzed by BrdU assay, MTT assay, and real-time cell analysis (RTCA). As indicated by BrdU and MTT, curcumin significantly decreased the cell proliferation of five cell lines (HT1080, SW872, SYO1, 1273, and U2197) and the viability of two cell lines (SW872 and SW982). VAE led to significant decreases of proliferation in eight cell lines (HT1080, SW872, T778, MLS-402, SW982, SYO1, 1293, and U2197) and reduced viability in seven STS lines (HT1080, SW872, T778, MLS-402, SW982, SYO1, and 1273). As indicated by RTCA for 160 h, curcumin decreased the CI of all synovial sarcoma cell lines as well as T778 and HT1080. VAE diminished the CI in most of the synovial sarcoma (SW982, SYO1) and liposarcoma (SW872, T778) cell lines as well as HT1080. Primary fibroblasts were not affected adversely by the two compounds in RTCA. Curcumin and VAE can inhibit the proliferation and viability of STS cells.

Carcinosarcoma of the upper urinary tract with an aggressive angiosarcoma component.

PubMed

Cuadra-Urteaga, José Luis; Font, Albert; Tapia, Gustavo; Areal, Juan; Taron, Miquel

2016-01-01

Carcinosarcomas (CS) are biphasic tumors with malignant epithelial and mesenchymal elements. The sarcomatoid elements of CS can include chondrosarcoma, malignant fibrous histiocytoma, osteosarcoma, leiomyosarcoma, fibrosarcoma, or liposarcoma. CS of the upper urinary tract are extremely rare but are associated with a poor prognosis. We report a case of a 44-year-old man with a localized right renal pelvis mass treated with a right nephroureterectomy. The pathological examination showed a high-grade urothelial carcinoma of the renal pelvis, stage III (pT3aNxM0). A few days later, he developed lower back pain, hematuria, cough with hemoptoic sputum and progressive dyspnea. Radiological explorations showed multiple bilateral lung nodules and a retroperitoneal mass. A CT-guided biopsy of the retroperitoneal mass revealed a high-grade angiosarcoma. A review of the nephrectomy specimen showed a microscopic focus of angiosarcoma in the urothelial carcinoma. Therefore, the initial diagnosis was changed to CS of the renal pelvis with an angiosarcoma component. The patient developed progressive respiratory failure and died 8 weeks after surgery. An autopsy revealed a large retroperitoneal mass with metastatic nodules to the abdominal wall, diaphragm, small intestine, liver, spleen, and lung. All lesions were angiosarcoma, with no evidence of urothelial carcinoma. This is the first case reported of a patient with CS of the upper urinary tract with an angiosarcoma component with a very aggressive course that caused the immediate appearance of multiple angiosarcoma metastases. We also describe the clinical and molecular characteristics of CS, which will help to contribute to a better understanding of this type of tumor.

Carcinosarcoma of the upper urinary tract with an aggressive angiosarcoma component

PubMed Central

Cuadra-Urteaga, José Luis; Font, Albert; Tapia, Gustavo; Areal, Juan; Taron, Miquel

2016-01-01

ABSTRACT Carcinosarcomas (CS) are biphasic tumors with malignant epithelial and mesenchymal elements. The sarcomatoid elements of CS can include chondrosarcoma, malignant fibrous histiocytoma, osteosarcoma, leiomyosarcoma, fibrosarcoma, or liposarcoma. CS of the upper urinary tract are extremely rare but are associated with a poor prognosis. We report a case of a 44-year-old man with a localized right renal pelvis mass treated with a right nephroureterectomy. The pathological examination showed a high-grade urothelial carcinoma of the renal pelvis, stage III (pT3aNxM0). A few days later, he developed lower back pain, hematuria, cough with hemoptoic sputum and progressive dyspnea. Radiological explorations showed multiple bilateral lung nodules and a retroperitoneal mass. A CT-guided biopsy of the retroperitoneal mass revealed a high-grade angiosarcoma. A review of the nephrectomy specimen showed a microscopic focus of angiosarcoma in the urothelial carcinoma. Therefore, the initial diagnosis was changed to CS of the renal pelvis with an angiosarcoma component. The patient developed progressive respiratory failure and died 8 weeks after surgery. An autopsy revealed a large retroperitoneal mass with metastatic nodules to the abdominal wall, diaphragm, small intestine, liver, spleen, and lung. All lesions were angiosarcoma, with no evidence of urothelial carcinoma. This is the first case reported of a patient with CS of the upper urinary tract with an angiosarcoma component with a very aggressive course that caused the immediate appearance of multiple angiosarcoma metastases. We also describe the clinical and molecular characteristics of CS, which will help to contribute to a better understanding of this type of tumor. PMID:26891233

Androgen Control of Cell Proliferation and Cytoskeletal Reorganization in Human Fibrosarcoma Cells

PubMed Central

Chauhan, Sanjay; Kunz, Susan; Davis, Kelli; Roberts, Jordan; Martin, Greg; Demetriou, Manolis C.; Sroka, Thomas C.; Cress, Anne E.; Miesfeld, Roger L.

2009-01-01

We recently generated an HT-1080-derived cell line called HT-AR1 that responds to dihydrotestosterone (DHT) treatment by undergoing cell growth arrest in association with cytoskeletal reorganization and induction of neuroendocrine-like cell differentiation. In this report, we show that DHT induces a dose-dependent increase in G0/G1 growth-arrested cells using physiological levels of hormone. The arrested cells increase in cell size and contain a dramatic redistribution of desmoplakin, keratin 5, and chromogranin A proteins. DHT-induced cytoskeletal changes were also apparent from time lapse video microscopy that showed that androgen treatment resulted in the rapid appearance of neuronal-like membrane extensions. Expression profiling analysis using RNA isolated from DHT-treated HT-AR1 cells revealed that androgen receptor activation leads to the coordinate expression of numerous cell signaling genes including RhoB, PTGF-β, caveolin-2, Egr-1, myosin 1B, and EHM2. Because RhoB has been shown to have a role in tumor suppression and neuronal differentiation in other cell types, we investigated RhoB signaling functions in the HT-AR1 steroid response. We found that steroid induction of RhoB was DHT-specific and that newly synthesized RhoB protein was post-translationally modified and localized to endocytic vesicles. Moreover, treatment with a farnesyl transferase inhibitor reduced DHT-dependent growth arrest, suggesting that prenylated RhoB might function to inhibit HT-AR1 cell proliferation. This was directly shown by transfecting HT-AR1 cells with RhoB coding sequences containing activating or dominant negative mutations. PMID:14576147

IGF1R- and ROR1-Specific CAR T Cells as a Potential Therapy for High Risk Sarcomas

PubMed Central

Huang, Xin; Park, Haein; Greene, Joseph; Zhou, Sophia X.; Albert, Catherine M.; Moy, Fred; Sachdev, Deepali; Yee, Douglas; Rader, Christoph; Hamby, Carl V.; Loeb, David M.; Cairo, Mitchell S.; Zhou, Xianzheng

2015-01-01

Patients with metastatic or recurrent and refractory sarcomas have a dismal prognosis. Therefore, new targeted therapies are urgently needed. This study was designed to evaluate chimeric antigen receptor (CAR) T cells targeting the type I insulin-like growth factor receptor (IGF1R) or tyrosine kinase-like orphan receptor 1 (ROR1) molecules for their therapeutic potential against sarcomas. Here, we report that IGF1R (15/15) and ROR1 (11/15) were highly expressed in sarcoma cell lines including Ewing sarcoma, osteosarcoma, alveolar or embryonal rhabdomyosarcoma, and fibrosarcoma. IGF1R and ROR1 CAR T cells derived from eight healthy donors using the Sleeping Beauty (SB) transposon system were cytotoxic against sarcoma cells and produced high levels of IFN-γ, TNF-α and IL-13 in an antigen-specific manner. IGF1R and ROR1 CAR T cells generated from three sarcoma patients released significant amounts of IFN-γ in response to sarcoma stimulation. The adoptive transfer of IGF1R and ROR1 CAR T cells derived from a sarcoma patient significantly reduced tumor growth in pre-established, systemically disseminated and localized osteosarcoma xenograft models in NSG mice. Infusion of IGF1R and ROR1 CAR T cells also prolonged animal survival in a localized sarcoma model using NOD/scid mice. Our data indicate that both IGF1R and ROR1 can be effectively targeted by SB modified CAR T cells and that such CAR T cells may be useful in the treatment of high risk sarcoma patients. PMID:26173023

Depletion of RIPK3 or MLKL blocks TNF-driven necroptosis and switches towards a delayed RIPK1 kinase-dependent apoptosis

PubMed Central

Remijsen, Q; Goossens, V; Grootjans, S; Van den Haute, C; Vanlangenakker, N; Dondelinger, Y; Roelandt, R; Bruggeman, I; Goncalves, A; Bertrand, M J M; Baekelandt, V; Takahashi, N; Berghe, T V; Vandenabeele, P

2014-01-01

In human cells, the RIPK1–RIPK3–MLKL–PGAM5–Drp1 axis drives tumor necrosis factor (TNF)-induced necroptosis through mitochondrial fission, but whether this pathway is conserved among mammals is not known. To answer this question, we analyzed the presence and functionality of the reported necroptotic axis in mice. As in humans, knockdown of receptor-interacting kinase-3 (RIPK3) or mixed lineage kinase domain like (MLKL) blocks TNF-induced necroptosis in L929 fibrosarcoma cells. However, repression of either of these proteins did not protect the cells from death, but instead induced a switch from TNF-induced necroptosis to receptor-interacting kinase-1 (RIPK1) kinase-dependent apoptosis. In addition, although mitochondrial fission also occurs during TNF-induced necroptosis in L929 cells, we found that knockdown of phosphoglycerate mutase 5 (PGAM5) and dynamin 1 like protein (Drp1) did not markedly protect the cells from TNF-induced necroptosis. Depletion of Pink1, a reported interactor of both PGAM5 and Drp1, did not affect TNF-induced necroptosis. These results indicate that in these murine cells mitochondrial fission and Pink1 dependent processes, including Pink-Parkin dependent mitophagy, apparently do not promote necroptosis. Our data demonstrate that the core components of the necrosome (RIPK1, RIPK3 and MLKL) are crucial to induce TNF-dependent necroptosis both in human and in mouse cells, but the associated mechanisms may differ between the two species or cell types. PMID:24434512

IGF1R- and ROR1-Specific CAR T Cells as a Potential Therapy for High Risk Sarcomas.

PubMed

Huang, Xin; Park, Haein; Greene, Joseph; Pao, James; Mulvey, Erin; Zhou, Sophia X; Albert, Catherine M; Moy, Fred; Sachdev, Deepali; Yee, Douglas; Rader, Christoph; Hamby, Carl V; Loeb, David M; Cairo, Mitchell S; Zhou, Xianzheng

2015-01-01

Patients with metastatic or recurrent and refractory sarcomas have a dismal prognosis. Therefore, new targeted therapies are urgently needed. This study was designed to evaluate chimeric antigen receptor (CAR) T cells targeting the type I insulin-like growth factor receptor (IGF1R) or tyrosine kinase-like orphan receptor 1 (ROR1) molecules for their therapeutic potential against sarcomas. Here, we report that IGF1R (15/15) and ROR1 (11/15) were highly expressed in sarcoma cell lines including Ewing sarcoma, osteosarcoma, alveolar or embryonal rhabdomyosarcoma, and fibrosarcoma. IGF1R and ROR1 CAR T cells derived from eight healthy donors using the Sleeping Beauty (SB) transposon system were cytotoxic against sarcoma cells and produced high levels of IFN-γ, TNF-α and IL-13 in an antigen-specific manner. IGF1R and ROR1 CAR T cells generated from three sarcoma patients released significant amounts of IFN-γ in response to sarcoma stimulation. The adoptive transfer of IGF1R and ROR1 CAR T cells derived from a sarcoma patient significantly reduced tumor growth in pre-established, systemically disseminated and localized osteosarcoma xenograft models in NSG mice. Infusion of IGF1R and ROR1 CAR T cells also prolonged animal survival in a localized sarcoma model using NOD/scid mice. Our data indicate that both IGF1R and ROR1 can be effectively targeted by SB modified CAR T cells and that such CAR T cells may be useful in the treatment of high risk sarcoma patients.

FOXM1 in sarcoma: role in cell cycle, pluripotency genes and stem cell pathways.

PubMed

Kelleher, Fergal C; O'Sullivan, Hazel

2016-07-05

FOXM1 is a pro-proliferative transcription factor that promotes cell cycle progression at the G1-S, and G2-M transitions. It is activated by phosphorylation usually mediated by successive cyclin - cyclin dependent kinase complexes, and is highly expressed in sarcoma. p53 down regulates FOXM1 and FOXM1 inhibition is also partly dependent on Rb and p21. Abnormalities of p53 or Rb are frequent in sporadic sarcomas with bone or soft tissue sarcoma, accounting for 36% of index cancers in the high penetrance TP53 germline disorder, Li-Fraumeni syndrome.FOXM1 stimulates transcription of pluripotency related genes including SOX2, KLF4, OCT4, and NANOG many of which are important in sarcoma, a disorder of mesenchymal stem cell/ partially committed progenitor cells. In a selected specific, SOX2 is uniformly expressed in synovial sarcoma. Embryonic pathways preferentially used in stem cell such as Hippo, Hedgehog, and Wnt dominate in FOXM1 stoichiometry to alter rates of FOXM1 production or degradation. In undifferentiated pleomorphic sarcoma, liposarcoma, and fibrosarcoma, dysregulation of the Hippo pathway increases expression of the effector co-transcriptional activator Yes-Associated Protein (YAP). A complex involving YAP and the transcription factor TEAD elevates FOXM1 in these sarcoma subtypes. In another scenario 80% of desmoid tumors have nuclear localization of β-catenin, the Wnt pathway effector molecule. Thiazole antibiotics inhibit FOXM1 and because they have an auto-regulator loop FOXM1 expression is also inhibited. Current systemic treatment of sarcoma is of limited efficacy and inhibiting FOXM1 represents a potential new strategy.

Control of erythropoietin gene expression and its use in medicine.

PubMed

Jelkmann, Wolfgang

2007-01-01

Erythropoietin (EPO) gene expression is under the control of inhibitory (GATA-2, NF-kappaB) and stimulatory (hypoxia-inducible transcription factor [HIF]-2, hepatocyte nuclear factor [HNF]-4alpha [alpha]) transcription factors. EPO deficiency is the main cause of the anemia in chronic kidney disease (CKD) and a contributing factor in the anemias of inflammation and cancer. Small, orally active compounds capable of stimulating endogenous EPO production are in preclinical or clinical trials for treatment of anemia. These agents include stabilizers of the HIFs that bind to the EPO enhancer and GATA inhibitors which prevent GATA from suppressing the EPO promoter. While HIF stabilizing drugs may prove useful as inexpensive second-line choices, at present, their side effects--particularly tumorigenicity--preclude their use as first-choice therapy. As an alternative, EPO gene therapy has been explored in animal studies and in trials on CKD patients. Here, a major problem is immunogenicity of ex vivo transfected implanted cells and of the recombinant protein produced after ex vivo or in vivo EPO complementary DNA (cDNA) transfer. Recombinant human EPO (rhEPO) engineered in Chinese hamster ovary (CHO) cell cultures (epoetin alpha and epoetin beta [beta]) and its hyperglycosylated analogue darbepoetin alpha are established and safe drugs to avoid allogeneic red blood cell transfusion. Gene-activated EPO (epoetin delta [delta]) from human fibrosarcoma cells (HT-1080) has recently been launched for use in CKD. It is important to know the basics of the technologies, production processes, and structural properties of the novel anti-anemic strategies and drugs.

Evaluation of matrix metalloproteinases (MMP)-2 and MMP-9 activity in serum and biochemical and hematological parameters in spontaneous canine cutaneous tumors before and after surgical treatment.

PubMed

Fathipour, Vahid; Khaki, Zohreh; Nassiri, Seyyed Mehdi

2018-01-01

Recently, matrix metalloproteinases (MMP), in particular the gelatinases MMP-2 and MMP-9, generally considered as tumor markers for clinical applications. A longitudinal 2-years follow-up survey was performed on dogs with cutaneous tumor. Serum samples were obtained from 22 dogs with different cutaneous tumors and 22 health dogs at the time of surgery and one month, three months and one year after surgery. Gelatin zymography, hematological and biochemical assessment were performed for all serum samples. The serum alkaline phosphatase activity in dogs with malignant tumors was significantly higher than that in dogs with benign tumors and control cases. Latent forms of MMP-2 and MMP-9 were detected in all of the tumor cases. Gelatin zymography showed active form of MMP-9 in 12 cases (three benign and nine malignant tumors) and active form of MMP-2 in one fibrosarcoma case. Serum activity of active-MMP-9 and total MMP-9 was significantly higher in dogs with cutaneous tumors than those in controls. Tumor cases had higher serum activity of active-MMP-9 rather than controls. MMPs and alkaline phosphatase activities in serum were decreased significantly after surgery. Only one case with perianal gland adenoma showed recurrence of tumor four months after surgery in which active form of MMP-9 had identified one month before recurrence. According to the findings, it will be useful to measure ALP, MMP-2 and MMP-9 activities in the serum of dogs with cutaneous tumor for determination of tumor behavior before surgical treatment.

Sorafenib paradoxically activates the RAS/RAF/ERK pathway in polyclonal human NK cells during expansion and thereby enhances effector functions in a dose- and time-dependent manner.

PubMed

Lohmeyer, J; Nerreter, T; Dotterweich, J; Einsele, H; Seggewiss-Bernhardt, R

2018-03-24

Natural killer (NK) cells play a major role in host immunity against leukaemia and lymphoma. However, clinical trials applying NK cells have not been as efficient as hoped for. Patients treated with rapidly accelerated fibrosarcoma (RAF) inhibitors exhibit increased tumour infiltration by immune cells, suggesting that a combination of RAF inhibitors with immunotherapy might be beneficial. As mitogen-activated protein kinases (MAPKs) such as raf-1 proto-oncogene, serine/threonine kinase (CRAF) regulate NK cell functions, we performed an in-vitro investigation on the potential of clinically relevant short-acting tyrosine kinase inhibitors (TKIs) as potential adjuvants for NK cell therapy: NK cells from healthy human blood donors were thus treated with sorafenib, sunitinib or the pan-RAF inhibitor ZM336372 during ex-vivo expansion. Functional outcomes assessed after washout of the drugs included cytokine production, degranulation, cytotoxicity, apoptosis induction and signal transduction with/without target cell contact. Paradoxically, sorafenib enhanced NK cell effector functions in a time- and dose-dependent manner by raising the steady-state activation level. Of note, this did not lead to NK cell exhaustion, but enhanced activity against target cells such as K562 or Daudis mediated via the RAS/RAF/extracellular-regulated kinase (ERK) pathway, but not via protein kinase B (AKT). Our data will pave the path to develop a rationale for the considered use of RAF inhibitors such as sorafenib for pre-activation in NK cell-based adoptive immune therapy. © 2018 British Society for Immunology.

Antitumor effects of a tumor cell vaccine expressing a membrane-bound form of the IL-12 p35 subunit.

PubMed

Lim, Ho Yong; Ju, Hee Young; Chung, Hee-Yong; Kim, Young Sang

2010-08-15

We investigated whether expression of the IL-12 p35 subunit in membrane-bound form in tumor cells enhanced their immunogenicity. Since p35 is only secreted when associated with the IL-12 p40 subunit, we generated tumor cells expressing membrane-bound forms of p35 and p40 as chimeras with the transmembrane/cytoplasmic region of TNFα (mbIL-12p35 and mbIL-12p40). The relevant vectors were transfected into MethA fibrosarcoma cells, and mbIL-12p35 or mbIL-12p40-expressing tumor clones were isolated and their ability to induce antitumor immunity studied. Cells of the mbIL-12p35 tumor clone induced CD69 expression and IFNγ production in purified CD8(+) T cells in vitro, and their in vivo tumorigenicity was reduced. Cells of the mbIL-12p40 tumor clone failed to show either of these activities. Mice that had rejected cells of the mbIL-12p35 tumor clone possessed systemic antitumor immunity to wild type tumor cells. The growth rate of mbIL-12p35 tumor cells was greater in CD8(+) T cell-depleted mice than in CD4(+) T-cell- and NK cell-depleted mice or normal mice, suggesting that CD8(+) T cells were mainly responsible for the antitumor immunity. These results indicate that expression of mbIL-12p35 on tumor cells enhances their immunogenicity by increasing their ability to activate CD8(+) T cells, possibly by direct priming.

Tumor targeting of gene expression through metal-coordinated conjugation with dextran.

PubMed

Hosseinkhani, Hossein; Aoyama, Teruyoshi; Ogawa, Osamu; Tabata, Yasuhiko

2003-03-07

Tumor targeting of plasmid DNA was achieved through the conjugation of dextran derivatives with chelate residues based on metal coordination. Diethylenetriamine pentaacetic acid (DTPA), spermidine (Sd), and spermine (Sm) were chemically introduced to the hydroxyl groups of dextran to obtain dextran-DTPA, dextran-Sd and dextran-Sm derivatives. Conjugation of the dextran derivative by Zn(2+) coordination decreased the apparent size of the plasmid DNA, depending on the derivative type. The negative zeta potential of plasmid DNA became almost 0 mV after Zn(2+)-coordinated conjugation with dextran-Sm. When the dextran derivative-plasmid DNA conjugates with Zn(2+) coordination were intravenously injected subcutaneously into mice bearing Meth-AR-1 fibrosarcoma, the dextran-Sm-plasmid DNA conjugate significantly enhanced the level of gene expression in the tumor, in contrast to the conjugate of other dextran derivatives and free plasmid DNA. The enhanced gene expression produced by the Zn(2+)-coordinated dextran-Sm-plasmid DNA conjugate was specific to the tumor, whereas a simple mixture of dextran-Sm and plasmid DNA was not effective. The level of gene expression depended on the percentage of chelate residues introduced, the mixing weight ratio of the plasmid DNA/Sm residue used for conjugate preparation, and the plasmid DNA dose. A fluorescent microscopic study revealed that localization of plasmid DNA in the tumor tissue was observed only after injection of the dextran-Sm-plasmid DNA conjugate with Zn(2+) coordination. In addition, the gene expression induced by the conjugate lasted for more than 10 days after the injection. We conclude that Zn(2+)-coordinated dextran-Sm conjugation is a promising way to enable plasmid DNA to target the tumor in gene expression as well as to prolong the duration of gene expression.

Binding and internalization of NGR-peptide-targeted liposomal doxorubicin (TVT-DOX) in CD13-expressing cells and its antitumor effects.

PubMed

Garde, Seema V; Forté, André J; Ge, Michael; Lepekhin, Eugene A; Panchal, Chandra J; Rabbani, Shafaat A; Wu, Jinzi J

2007-11-01

In an effort to develop new agents and molecular targets for the treatment of cancer, aspargine-glycine-arginine (NGR)-targeted liposomal doxorubicin (TVT-DOX) is being studied. The NGR peptide on the surface of liposomal doxorubicin (DOX) targets an aminopeptidase N (CD13) isoform, specific to the tumor neovasculature, making it a promising strategy. To further understand the molecular mechanisms of action, we investigated cell binding, kinetics of internalization as well as cytotoxicity of TVT-DOX in vitro. We demonstrate the specific binding of TVT-DOX to CD13-expressing endothelial [human umbilical vein endothelial cells (HUVEC) and Kaposi sarcoma-derived endothelial cells (SLK)] and tumor (fibrosarcoma, HT-1080) cells in vitro. Following binding, the drug was shown to internalize through the endosomal pathway, eventually leading to the localization of doxorubicin in cell nuclei. TVT-DOX showed selective toxicity toward CD13-expressing HUVEC, sparing the CD13-negative colon-cancer cells, HT-29. Additionally, the nontargeted counterpart of TVT-DOX, Caelyx, was less cytotoxic to the CD13-positive HUVECs demonstrating the advantages of NGR targeting in vitro. The antitumor activity of TVT-DOX was tested in nude mice bearing human prostate-cancer xenografts (PC3). A significant growth inhibition (up to 60%) of PC3 tumors in vivo was observed. Reduction of tumor vasculature following treatment with TVT-DOX was also apparent. We further compared the efficacies of TVT-DOX and free doxorubicin in the DOX-resistant colon-cancer model, HCT-116, and observed the more pronounced antitumor effects of the TVT-DOX formulation over free DOX. The potential utility of TVT-DOX in a variety of vascularized solid tumors is promising.

Hepatic carcinosarcoma: evidence of polyclonal origin based on microsatellite analysis.

PubMed

Gu, Yi-Jin; Zhu, Yu-Yao; Lu, Xin-Yuan; Zhao, Qian; Cong, Wen-Ming

2015-12-01

Hepatic carcinosarcoma (HCS) is an aggressive tumor for which a consensus regarding the clonal origin has not yet been reached. The aim of the study was to identify the origin of the hepatocellular carcinoma (HCC) and sarcoma components in HCS. We chose microsatellite technique containing loss of heterozygosity (LOH) and microsatellite instability (MSI) on three HCS patients who underwent curative resection confirmed by pathological examination. Tumors were firstly analyzed for Hep Par 1, CK18, CD10, CD117, SMA and vimentin expression by immunohistochemistry. LOH and MSI were then investigated. The incidence rate of LOH/MSI in all nine MS was calculated as the fractional allelic loss (FAL) index, which was internationally recognized standard. A FAL<30% was representative of a monoclonal origin and a FAL≥30% indicated a polyclonal origin. All patients were positive for HBsAg. Microscopic examination showed HCS containing two different cell types: a fibrosarcoma component with spindle cells and an HCC population of cells with a trabecular pattern. In the HCC tumor portions, Hep Par 1, CK18, CD10 were expressed while vimentin was not. In contrast, the spindle cell populations were positive for vimentin and negative for Hep Par 1, CK18, CD10. The highest frequencies of LOH and MSI were at the D16S505 (2/3; 66.7%), D17S831 (2/3; 66.7%) and D17S938 MS (2/3; 66.7%). The FALs for the three cases of HCS were 50% (4/8), 55.6% (5/9) and 33.3% (3/9), suggesting a polyclonal origin. Immunohistochemistry and analysis of LOH and MSI strongly demonstrated that the three HCS samples were consistent with a polyclonal origin for all three cases. Copyright © 2015 Elsevier GmbH. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Taylor, G.N.; Lloyd, R.D.; Mays, C.W.

Plutonium-239 or 241Am administered intravenously in the monomeric citrate form was initially deposited in beagle livers principally in the hepatocytes and to a much lesser extent in the sinusoidal macrophages and connective tissues. The initial distribution was quite uniform throughout the hepatic parenchyma; however, at later postinjection intervals, depending on the amount of injected activity, the liver burden became increasingly more focal due to: (1) a progressive shift of the radionuclide from the hepatic epithelium to the macrophages; (2) the movement of such macrophages toward the portal or central regions of the lobule; and (3) the displacement of the oldermore » more radioactive tissue by regenerating hepatocytes, which generally have a much lower radionuclide content. The hepatic lesions produced by Pu or Am included: (1) necrosis and degenerative changes that were clinically serious or fatal in some of the animals injected with approximately 107 kBq kg-1; (2) marked structural and circulatory changes resulting from necrosis and focal hepatocyte hyperplasia; (3) a significant incidence of both benign and malignant primary liver tumors. In both Pu- and Am-treated dogs, the most frequently appearing neoplasm was the bile duct adenoma, followed by the cholangiocarcinoma. The most obvious difference between Pu- and Am-induced liver neoplasia was the greater frequency of fibrosarcomas and mast cell sarcomas in the Am-treated groups. Hepatomas were of relatively low frequency in animals with Pu or Am burdens. Although the incidence of bone neoplasia was high among the dogs in these studies, the risk of liver tumors, especially in the Am-treated animals, exceeded that of the skeleton in some of the lower dosage levels where the survival times were long.« less

Elucidation of flow-mediated tumour cell-induced platelet aggregation using an ultrasound standing wave trap.

PubMed

Bazou, D; Santos-Martinez, M J; Medina, C; Radomski, M W

2011-04-01

Tumour cells activate and aggregate platelets [tumour cell-induced platelet aggregation (TCIPA)] and this process plays an important role in the successful metastasis of cancer cells. To date, most studies on TCIPA have been conducted under no-flow conditions. In this study, we have investigated TCIPA in real time under flow conditions, using an ultrasound standing wave trap that allows formation and levitation of cancer cell clusters in suspension, thus mimicking the conditions generated by flowing blood. Using 59M adenocarcinoma and HT1080 fibrosarcoma cells and human platelets, cancer cell cluster-platelet aggregates were imaged in real time using epi-fluorescence microscopy (F-actin) and investigated in detail using confocal microscopy (matrix metalloproteinase-2-GPIIb/IIIa co-localization) and scanning electron and helium-ion microscopy (<1 nm resolution). The release of gelatinases from aggregates was studied using zymography. We found that platelet activation and aggregation takes place on the surface of cancer cells (TCIPA), leading to time-dependent disruption of cancer cell clusters. Pharmacological modulation of TCIPA revealed that EDTA, prostacyclin, o-phenanthroline and apyrase significantly down-regulated TCIPA and, in turn, delayed cell cluster disruption, However, EGTA and aspirin were ineffective. Pharmacological inhibition of TCIPA correlated with the down-regulation of platelet activation as shown by flow-cytometry assay of platelet P-selectin. Our results show for the first time, that during TCIPA, platelet activation disrupts cancer cell clusters and this can contribute to metastasis. Thus, selective targeting of platelet aggregate-cancer cell clusters may be an important strategy to control metastasis. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

Modified Gompertz equation for electrotherapy murine tumor growth kinetics: predictions and new hypotheses

PubMed Central

2010-01-01

Background Electrotherapy effectiveness at different doses has been demonstrated in preclinical and clinical studies; however, several aspects that occur in the tumor growth kinetics before and after treatment have not yet been revealed. Mathematical modeling is a useful instrument that can reveal some of these aspects. The aim of this paper is to describe the complete growth kinetics of unperturbed and perturbed tumors through use of the modified Gompertz equation in order to generate useful insight into the mechanisms that underpin this devastating disease. Methods The complete tumor growth kinetics for control and treated groups are obtained by interpolation and extrapolation methods with different time steps, using experimental data of fibrosarcoma Sa-37. In the modified Gompertz equation, a delay time is introduced to describe the tumor's natural history before treatment. Different graphical strategies are used in order to reveal new information in the complete kinetics of this tumor type. Results The first stage of complete tumor growth kinetics is highly non linear. The model, at this stage, shows different aspects that agree with those reported theoretically and experimentally. Tumor reversibility and the proportionality between regions before and after electrotherapy are demonstrated. In tumors that reach partial remission, two antagonistic post-treatment processes are induced, whereas in complete remission, two unknown antitumor mechanisms are induced. Conclusion The modified Gompertz equation is likely to lead to insights within cancer research. Such insights hold promise for increasing our understanding of tumors as self-organizing systems and, the possible existence of phase transitions in tumor growth kinetics, which, in turn, may have significant impacts both on cancer research and on clinical practice. PMID:21029411

Cytostatic action of two nitrosoureas derived from cysteamine.

PubMed Central

Bourut, C.; Chenu, E.; Godenèche, D.; Madelmont, J. C.; Maral, R.; Mathé, G.; Meyniel, G.

1986-01-01

2-Chloroethyl nitrosocarbamoylcystamine or ICIG-1325 (CNCC) is a lipid-soluble isomeric mixture of nitrosoureas. Its dose-effect relationship on L1210 leukaemia is characterized by a large maximally efficient dose-range (MEDR), greater than that of other nitrosoureas. CNCC also demonstrated significant therapeutic activity on intracerebrally (i.c.) transplanted L1210 leukaemia and on six transplanted solid tumours, TM2 mammary carcinoma, M555 ovarian carcinoma, B16 melanoma, glioma 26, 3LL, Lewis lung carcinoma and colon 26 carcinoma. It was inactive on fibrosarcoma ICIG-Ci4. Its antitumour activity spectrum is wider than that of the related compounds 2-[3-(2-chloroethyl) 3-nitrosoureido]D-glucopyranose (CZT), (chloro-2-ethyl)-1(ribofuranosyl-isopropylidene-2'-3' paranitrobenzoate-5')-3 nitrosourea (RFCNU), and (chloro-2-ethyl)-1 (ribopyranosyl triacetate-2'-3'-4')-3 nitrosourea (RPCNU). A study of its metabolic disposition in animals has shown that CNCC undergoes extensive first-pass metabolism leading to the formation of four main plasma metabolites. These metabolites are water-soluble nitrosoureas that arose from the bioreduction of the disulphide bridge followed by the methylation and the oxidation of the thiol groups. Experimental screening was performed with these chemically synthesized metabolites. Both N'-(2-chloroethyl)-N-[2-(methylsulphinyl)ethyl]-N'-nitrosourea (CMSOEN2) and N'-(2-chloroethyl)-N-[2-(methylsulphonyl)ethyl]-N'-nitrosourea (CMSO2EN2) are very active on L1210 leukaemia grafted intraperitoneally (i.p.) and i.c., L40 leukaemia, B16 melanoma, glioma 26 and Lewis lung carcinoma. Their effectiveness is better than that of the parent compound CNCC. In addition,the percentage of mice cured after CMSOEN2 or CMSO2EN2 treatment is increased especially on B16 melanoma and glioma 26.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3801787

Subcellular localization patterns and their relationship to photodynamic activity of pyropheophorbide-a derivatives.

PubMed

MacDonald, I J; Morgan, J; Bellnier, D A; Paszkiewicz, G M; Whitaker, J E; Litchfield, D J; Dougherty, T J

1999-11-01

To determine if subcellular localization is important to photodynamic therapy (PDT) efficacy, an in vitro fluorescence microscopy study was conducted with a congeneric series of pyropheophorbide-a derivatives in human pharyngeal squamous cell carcinoma (FaDu) cells and murine radiation-induced fibrosarcoma (RIF) mutant cells. In the FaDu cells the octyl, decyl and dodecyl ether derivatives localized to the lysosomes at extracellular concentrations less than needed to produce a 50% cell kill (LD50). At extracellular concentrations equal or greater than the LD50 the compounds localized mainly to mitochondria. The propyl, pentyl, hexyl and heptyl ether derivatives localized mainly to the mitochondria at all concentrations studied. This suggested that mitochondria are a sensitive PDT target for these derivatives. Similar experiments were performed with two Photofrin-PDT resistant RIF cell lines, one of which was found to be resistant to hexyl ether derivative (C6) mediated-PDT and the other sensitive to C6-PDT relative to the parent line. At extracellular concentrations of C6 below the LD50 of each cell line, the mutants exhibited lysosomal localization. At concentrations above these values the patterns shifted to a mainly mitochondrial pattern. In these cell lines mitochondrial localization also correlated with PDT sensitivity. Localization to mitochondria or lysosomes appeared to be affected by the aggregation state of the congeners, all of which are highly aggregated in aqueous medium. Monomers apparently were the active fraction of these compounds because equalizing the extracellular monomer concentrations produced equivalent intracellular concentrations, photoxicity and localization patterns. Compounds that were mainly aggregates localized to the lysosomes where they were rendered less active. Mitochondria appear to be a sensitive target for pyropheophorbide-a-mediated photodamage, and the degree of aggregation seems to be a determinant of the localization site.

Investigating the impact of oxygen concentration and blood flow variation on photodynamic therapy

NASA Astrophysics Data System (ADS)

Penjweini, Rozhin; Kim, Michele M.; Finlay, Jarod C.; Zhu, Timothy C.

2016-03-01

Type II photodynamic therapy (PDT) is used for cancer treatment based on the combined action of a photosensitizer, a special wavelength of light, oxygen (3O2) and generation of singlet oxygen (1O2). Intra-patient and inter-patient variability of oxygen concentration ([3O2]) before and after the treatment as well as photosensitizer concentration and hemodynamic parameters such as blood flow during PDT has been reported. Simulation of these variations is valuable, as it would be a means for the rapid assessment of treatment effect. A mathematical model has been previously developed to incorporate the diffusion equation for light transport in tissue and the macroscopic kinetic equations for simulation of [3O2], photosensitizers in ground and triplet states and concentration of the reacted singlet oxygen ([1O₂]rx) during PDT. In this study, the finite-element based calculation of the macroscopic kinetic equations is done for 2-(1- Hexyloxyethyl)-2-devinyl pyropheophorbide (HPPH)-mediated PDT by incorporating the information of the photosensitizer photochemical parameters as well as the tissue optical properties, photosensitizer concentration, initial oxygen concentration ([3O2]0), blood flow changes and Φ that have been measured in mice bearing radiation-induced fibrosarcoma (RIF) tumors. Then, [1O2]rx calculated by using the measured [3O2] during the PDT is compared with [1O2]rx calculated based on the simulated [3O₂]; both calculations showed a reasonably good agreement. Moreover, the impacts of the blood flow changes and [3O2]0 on [1O2]rx have been investigated, which showed no pronounced effect of the blood flow changes on the long-term 1O2 generation. When [3O2]0 becomes limiting, small changes in [3O₂] have large effects on [1O2]rx.

Clinicopathological Characteristics of Mitotically-active Cellular Fibroma of the Ovary: A Single-institutional Experience.

PubMed

Kim, Ji-Ye; Na, Kiyong; Kim, Hyun-Soo

2017-05-01

Mitotically-active cellular fibroma (MACF) is a rare form of ovarian fibromatous tumor. Although it is generally acknowledged to have indolent biological behavior, its rarity and overlapping histopathological features with more common and aggressive entities make MACF prone to misdiagnosis and overtreatment. The clinicopathological characteristics of ovarian MACF have not been clearly established. Our 10-year review of cellular fibromatous tumors of the ovary diagnosed at a single institution revealed four cases of cellular fibroma (CF) and three cases of MACF. The mean age of patients with MACF was 46 years (range=20-71 years). Patients presented with symptoms related to pelvic masses, such as abdominal pain and discomfort and flank pain. Serum levels of cancer antigen 125 was increased in two patients with MACF. All cases of MACF were a single unilateral tumor. Magnetic resonance imaging revealed solid or mixed solid and cystic ovarian masses with diameters of 7.3-14.9 cm. The radiological impressions included benign stromal tumor, benign epithelial tumor, and borderline epithelial tumor. Grossly, MACFs exhibited yellow-to-tan fleshy cut surfaces, without necrosis or hemorrhage. Extensive hyaline degeneration, resulting in a fibrotic cut surface, was observed in one case. Histologically, MACF displayed frequent mitotic figures, as well as increased cellularity and mild cytological atypia. The mean mitotic count was 8.7 per 10 high-power fields. MACF is a newly-recognized subtype of ovarian cellular fibromatous tumor. Pathologists and clinicians should be aware of this rare entity to prevent misdiagnosis of MACF as fibrosarcoma or adult granulosa cell tumor and resultant overtreatment. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Enhancement of thermal response of normal and malignant tissues by Corynebacterium parvum. [Mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Urano, M.; Yamashita, T.; Suit, H.D.

1984-06-01

Further studies were carried out on the combined effects of Corynebacterium parvum and hyperthermia on animal tissues and cultured Chinese hamster ovary cells. Experimental animals were C3Hf/Sed mice derived from a defined flora mouse colony. Tumors were eighth-generation isotransplants of a spontaneous fibrosarcoma, FSa-II. Hyperthermia was given by immersing the mouse foot or culture flasks in the constant temperature water bath. Present experiments include thermal enhancement of C. parvum at different temperatures, effect of the agent on the kinetics of thermal resistance, and the mechanism of the thermal enhancement. The thermal enhancement by C. parvum was independent of temperature inmore » a range between 42.5 and 46.5 degrees, and it increased with decreasing temperature. The analysis of the Arrhenius plot suggested a comparable activation energy for combined treatments and for heat alone between 42.5 and 46.5 degrees. The thermal resistance developed very rapidly in both normal and tumor tissues. Systemic administration of C. parvum failed to modify the kinetics of thermal resistance. Several experiments were attempted in order to disclose the mechanism. A single injection of C. parvum-induced macrophages failed to enhance thermal response of the mouse foot, while 3 daily injections of the macrophages enhanced the response, indicating that the enhancement by C. parvum is at least partly attributed to the C. parvum-induced macrophages. Whole-body irradiation of 6 Gy and/or administration of anti-mouse T-cell serum and histamine failed to inhibit the C. parvum enhancement of thermal response. No thermal enhancement was observed for Chinese hamster ovary cells treated at 43.0 degrees in vitro with C. parvum or thiomersalate, a preservative supplemented in C. parvum, although cytotoxic effect was shown at a high concentration of thiomersalate.« less

A tracer dose of technetium-99m-labeled liposomes can estimate the effect of hyperthermia on intratumoral doxil extravasation.

PubMed

Kleiter, Miriam M; Yu, Daohai; Mohammadian, Lenore A; Niehaus, Nelsen; Spasojevic, Ivan; Sanders, Linda; Viglianti, Benjamin L; Yarmolenko, Pavel S; Hauck, Marlene; Petry, Neil A; Wong, Terence Z; Dewhirst, Mark W; Thrall, Donald E

2006-11-15

A noninvasive method to monitor intratumoral Doxil delivery in individual patients during targeted tumor therapy is important to predict treatment response. The purpose of this study was to determine if a small tracer dose of technetium-99m (99mTc)-labeled liposomes could be used to quantify the effect of local hyperthermia on intratumoral Doxil extravasation. Experiments were carried out in a rat fibrosarcoma model with transplanted thigh tumors. Liposomes of approximately same size and composition as Doxil were radiolabeled using [technetium-99m (99mTc)]exametazime. Eight treatment groups received either Doxil, a tracer dose or a large dose of 99mTc-labeled liposomes, or a combination of tracer and Doxil, with or without hyperthermia. This design was chosen to assure that coadministration of both liposomal formulations did not influence their intratumoral distribution. Hyperthermia was done for 45 minutes. Scintigraphic images were obtained at 5 and 18 hours. At 18 hours, tumors were removed and gamma counts as well as doxorubicin concentrations were measured. Intratumoral extravasation of the 99mTc-labeled tracer could be imaged scintigraphically under normothermic and hyperthermic conditions. The thermal enhancement ratio was slightly higher for radiolabeled liposomes than for doxorubicin concentration. However, there was a significant positive correlation of intratumoral doxorubicin concentration and intratumoral uptake of the radiolabeled tracer (expressed as percentage of the injected dose per gram of tissue). Coadministration of radiolabeled liposomes did not negatively influence the amount of drug delivered with Doxil. The use of a radiolabeled tracer has potential value to monitor drug delivery and estimate the effect of an intervention aimed to increase liposomal accumulation, such as local hyperthermia.

Vaccination with vascular progenitor cells derived from induced pluripotent stem cells elicits antitumor immunity targeting vascular and tumor cells.

PubMed

Koido, Shigeo; Ito, Masaki; Sagawa, Yukiko; Okamoto, Masato; Hayashi, Kazumi; Nagasaki, Eijiro; Kan, Shin; Komita, Hideo; Kamata, Yuko; Homma, Sadamu

2014-05-01

Vaccination of BALB/c mice with dendritic cells (DCs) loaded with the lysate of induced vascular progenitor (iVP) cells derived from murine-induced pluripotent stem (iPS) cells significantly suppressed the tumor of CMS-4 fibrosarcomas and prolonged the survival of CMS-4-inoculated mice. This prophylactic antitumor activity was more potent than that of immunization with DCs loaded with iPS cells or CMS-4 tumor cells. Tumors developed slowly in mice vaccinated with DCs loaded with iVP cells (DC/iVP) and exhibited a limited vascular bed. Immunohistochemistry and a tomato-lectin perfusion study demonstrated that the tumors that developed in the iVP-immunized mice showed a marked decrease in tumor vasculature. Immunization with DC/iVP induced a potent suppressive effect on vascular-rich CMS-4 tumors, a weaker effect on BNL tumors with moderate vasculature, and nearly no effect on C26 tumors with poor vasculature. Treatment of DC/iVP-immunized mice with a monoclonal antibody against CD4 or CD8, but not anti-asialo GM1, inhibited the antitumor activity. CD8(+) T cells from DC/iVP-vaccinated mice showed significant cytotoxic activity against murine endothelial cells and CMS-4 cells, whereas CD8(+) T cells from DC/iPS-vaccinated mice did not. DNA microarray analysis showed that the products of 29 vasculature-associated genes shared between genes upregulated by differentiation from iPS cells into iVP cells and genes shared by iVP cells and isolated Flk-1(+) vascular cells in CMS-4 tumor tissue might be possible targets in the immune response. These results suggest that iVP cells from iPS cells could be used as a cancer vaccine targeting tumor vascular cells and tumor cells.

Vascular endothelial growth factor-D is a key molecule that enhances lymphatic metastasis of soft tissue sarcomas

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yanagawa, Takashi, E-mail: tyanagaw@med.gunma-u.ac.jp; Shinozaki, Tetsuya; Watanabe, Hideomi

2012-04-15

Studies on lymph node metastasis of soft tissue sarcomas are insufficient because of its rarity. In this study, we examined the expressions of vascular endothelial growth factor (VEGF)-C and VEGF-D in soft tissue sarcomas metastasized to lymph nodes. In addition, the effects of the two molecules on the barrier function of a lymphatic endothelial cell monolayer against sarcoma cells were analyzed. We examined 7 patients who had soft tissue sarcomas with lymph node metastases and who had undergone neither chemotherapy nor radiotherapy before lymphadenectomy. Immunohistochemistry revealed that 2 of 7 sarcomas that metastasized to lymph nodes expressed VEGF-C both inmore » primary and metastatic lesions. On the other hand, VEGF-D expression was detected in 4 of 7 primary and 7 of 7 metastatic lesions, respectively. Interestingly, 3 cases that showed no VEGF-D expression at primary sites expressed VEGF-D in metastatic lesions. Recombinant VEGF-C at 10{sup -8} and VEGF-D at 10{sup -7}and 10{sup -8} g/ml significantly increased the random motility of lymphatic endothelial cells compared with controls. VEGF-D significantly increased the migration of sarcoma cells through lymphatic endothelial monolayers. The fact that VEGF-D induced the migration of fibrosarcomas through the lymphatic endothelial monolayer is the probable reason for the strong relationship between VEGF-D expression and lymph node metastasis in soft tissue sarcomas. The important propensities of this molecule for the increase of lymph node metastases are not only lymphangiogenesis but also down-regulation of the barrier function of lymphatic endothelial monolayers, which facilitates sarcoma cells entering the lymphatic circulation.« less

Vasculogenic Mimicry of HT1080 Tumour Cells In Vivo: Critical Role of HIF-1α-Neuropilin-1 Axis

PubMed Central

Misra, Roli M.; Bajaj, Manmohan S.; Kale, Vaijayanti P.

2012-01-01

HT1080 - a human fibrosarcoma-derived cell line – forms aggressive angiogenic tumours in immuno-compromised mice. In spite of its extensive use as a model of tumour angiogenesis, the molecular event(s) initiating the angiogenic program in these cells are not known. Since hypoxia stimulates tumour angiogenesis, we examined the hypoxia-induced events evoked in these cells. In contrast to cells grown under normoxic conditions, hypoxia-primed (1% O2) HT1080 cells formed robust tubules on growth factor-reduced matrigel and formed significantly larger tumours in xenograft models in a chetomin-sensitive manner, indicating the role of HIF-1α-mediated transcription in these processes. Immuno-histochemical analyses of tumours formed by GFP-expressing HT1080 cells clearly showed that the tumour cells themselves expressed various angiogenic markers including Neuropilin-1 (NRP-1) and formed functional vessels containing red blood cells, thereby unambiguously demonstrating the vasculogenic mimicry of HT1080 cells in vivo. Experiments performed with the HT1080 cells stably transfected with plasmid constructs expressing shNRP-1 or full-length NRP-1 clearly established that the HIF1α-mediated up-regulation of NRP-1 played a deterministic role in the process. Hypoxia-exposure resulted in an up-regulation of c-Myc and OCT3/4 and a down-regulation of KLF4 mRNAs, suggesting their involvement in the tumour formation and angiogenesis. However, silencing of NRP-1 alone, though not affecting proliferation in culture, was sufficient to abrogate the tumour formation completely; clearly establishing that the hypoxia-mediated HIF-1α-dependent up-regulation of NRP-1 is a critical molecular event involved in the vasculogenic mimicry and tumor formation by HT1080 cells in vivo. PMID:23185562

PNET-like features of synovial sarcoma of the lung: a pitfall in the cytologic diagnosis of soft-tissue tumors.

PubMed

Hummel, P; Yang, G C; Kumar, A; Cohen, J M; Winkler, B; Melamed, J; Scholes, J V; Jagirdar, J

2001-04-01

Fine-needle aspiration (FNA) cytology of soft-tissue tumors is evolving. As more experience is gained, we are becoming aware of potential pitfalls. We describe 2 cases of synovial sarcoma of the lung, primary and metastatic, in patients who had FNA biopsy performed on a lung mass. The cytologic smears showed extremely cellular groups of malignant small round cells, intersected by small blood vessels, with numerous loose single cells, in a background of macrophages and mature lymphocytes. The tumors displayed monomorphic cells forming rosettes and displaying occasional mitoses. A diagnosis of neuroendocrine tumor/primitive neuroepithelial tumor (PNET) was suspected. Furthermore, this suspicion was supported by immunohistochemical stains, which showed positivity for a neuroendocrine marker, Leu 7 (case 1), and for a neural marker, CD 99 (O 13 or HBA 71) (both cases); and negativity for cytokeratins (case 1). The resection specimen of case 1 had mostly tightly packed small round cells, with occasional rosettes, similar to the FNA biopsy, and focal areas composed of spindle cells, organized in a focal fibrosarcoma-like and hemangiopericytoma-like pattern. A balanced translocation between chromosomes X and 18, demonstrated by both karyotyping and fluorescent in situ hybridization (FISH), enabled us to make a diagnosis of synovial sarcoma, which was histologically classified as poorly differentiated. Case 2 was a metastatic biphasic synovial sarcoma of the arm, with a prominent epithelial component. Synovial sarcoma, when composed mainly of small round cells on cytologic smears, is a great mimicker of neuroendocrine/PNET tumors, with light microscopic and immunohistochemical overlap. Awareness of this potential pitfall may aid in preventing a misdiagnosis. Its recognition is of major concern, especially for the poorly differentiated variant, because it is associated with a worse prognosis. Copyright 2001 Wiley-Liss, Inc.

Targeted Delivery of Chemotherapeutic Agents Using Improved Radiosensitive Liquid Core Microcapsules and Assessment of Their Antitumor Effect

DOE Office of Scientific and Technical Information (OSTI.GOV)

Harada, Satoshi; Ehara, Shigeru; Ishii, Keizo

2009-10-01

Purpose: Radiation-sensitive microcapsules composed of alginate and hyaluronic acid are being developed. We report the development of improved microcapsules that were prepared using calcium- and yttrium-induced polymerization. We previously reported on the combined antitumor effect of carboplatin-containing microcapsules and radiotherapy. Methods and Materials: We mixed a 0.1% (wt/vol) solution of hyaluronic acid with a 0.2% alginate solution. Carboplatin (l mg) and indocyanine green (12.5 {mu}g) were added to this mixture, and the resultant material was used for capsule preparation. The capsules were prepared by spraying the material into a mixture containing a 4.34% CaCl{sub 2} solution supplemented with 0-0.01% yttrium.more » These capsules were irradiated with single doses of 0.5, 1.0, 1.5, or 2 Gy {sup 60}Co {gamma}-rays. Immediately after irradiation, the frequency of microcapsule decomposition was determined using a microparticle-induced X-ray emission camera. The amount of core content released was estimated by particle-induced X-ray emission and colorimetric analysis with 0.25% indocyanine green. The antitumor effect of the combined therapy was determined by monitoring its effects on the diameter of an inoculated Meth A fibrosarcoma. Results: Microcapsules that had been polymerized using a 4.34% CaCl{sub 2} solution supplemented with 5.0 x 10{sup -3}% (10{sup -3}% meant or 10%{sup -3}) yttrium exhibited the maximal decomposition, and the optimal release of core content occurred after 2-Gy irradiation. The microcapsules exhibited a synergistic antitumor effect combined with 2-Gy irradiation and were associated with reduced adverse effects. Conclusion: The results of our study have shown that our liquid core microcapsules can be used in radiotherapy for targeted delivery of chemotherapeutic agents.« less

Emerging roles of GLIS3 in neonatal diabetes, type 1 and type 2 diabetes.

PubMed

Wen, Xianjie; Yang, Yisheng

2017-02-01

GLI-similar 3 (GLIS3), a member of the Krüppel-like zinc finger protein subfamily, is predominantly expressed in the pancreas, thyroid and kidney. Glis3 mRNA can be initially detected in mouse pancreas at embryonic day 11.5 and is largely restricted to β cells, pancreatic polypeptide-expressing cells, as well as ductal cells at later stage of pancreas development. Mutations in GLIS3 cause a neonatal diabetes syndrome, characterized by neonatal diabetes, congenital hypothyroidism and polycystic kidney. Importantly, genome-wide association studies showed that variations of GLIS3 are strongly associated with both type 1 diabetes (T1D) and type 2 diabetes (T2D) in multiple populations. GLIS3 cooperates with pancreatic and duodenal homeobox 1 (PDX1), v-maf musculoaponeurotic fibrosarcoma oncogene family, protein A (MAFA), as well as neurogenic differentiation 1 (NEUROD1) and potently controls insulin gene transcription. GLIS3 also plays a role in β cell survival and likely in insulin secretion. Any perturbation of these functions may underlie all three forms of diabetes. GLIS3, synergistically with hepatocyte nuclear factor 6 (HNF6) and forkhead box A2 (FOXA2), controls fetal islet differentiation via transactivating neurogenin 3 (NGN3) and impairment of this function leads to neonatal diabetes. In addition, GLIS3 is also required for the compensatory β cell proliferation and mass expansion in response to insulin resistance, which if disrupted may predispose to T2D. The increasing understanding of the mechanisms of GLIS3 in β cell development, survival and function maintenance will provide new insights into disease pathogenesis and potential therapeutic target identification to combat diabetes. © 2017 Society for Endocrinology.

Direct Ca2+-dependent Heterophilic Interaction between Desmosomal Cadherins, Desmoglein and Desmocollin, Contributes to Cell–Cell Adhesion

PubMed Central

Chitaev, Nikolai A.; Troyanovsky, Sergey M.

1997-01-01

Human fibrosarcoma cells, HT-1080, feature extensive adherens junctions, lack mature desmosomes, and express a single known desmosomal protein, Desmoglein 2 (Dsg2). Transfection of these cells with bovine Desmocollin 1a (Dsc1a) caused dramatic changes in the subcellular distribution of endogenous Dsg2. Both cadherins clustered in the areas of the adherens junctions, whereas only a minor portion of Dsg2 was seen in these areas in the parental cells. Deletion mapping showed that intact extracellular cadherin-like repeats of Dsc1a (Arg1-Thr170) are required for the translocation of Dsg2. Deletion of the intracellular C-domain that mediates the interaction of Dsc1a with plakoglobin, or the CSI region that is involved in the binding to desmoplakin, had no effect. Coimmunoprecipitation experiments of cell lysates stably expressing Dsc1a with anti-Dsc or -Dsg antibodies demonstrate that the desmosomal cadherins, Dsg2 and Dsc1a, are involved in a direct Ca2+-dependent interaction. This conclusion was further supported by the results of solid phase binding experiments. These showed that the Dsc1a fragment containing cadherin-like repeats 1 and 2 binds directly to the extracellular portion of Dsg in a Ca2+-dependent manner. The contribution of the Dsg/ Dsc interaction to cell–cell adhesion was tested by coculturing HT-1080 cells expressing Dsc1a with HT-1080 cells lacking Dsc but expressing myc-tagged plakoglobin (MPg). In the latter cells, MPg and the endogenous Dsg form stable complexes. The observed specific coimmunoprecipitation of MPg by anti-Dsc antibodies in coculture indicates that an intercellular interaction between Dsc1 and Dsg is involved in cell–cell adhesion. PMID:9214392

Modulation of TEL transcription activity by interaction with the ubiquitin-conjugating enzyme UBC9

PubMed Central

Chakrabarti, Subhra Ranjan; Sood, Rashmi; Ganguly, Surajit; Bohlander, Stefan; Shen, Zhiyuan; Nucifora, Giuseppina

1999-01-01

The E-26 transforming specific (ETS)-related gene TEL, also known as ETV6, is involved in a large number of chromosomal rearrangements associated with leukemia and congenital fibrosarcoma. The encoded protein contains two functional domains: a helix–loop–helix (HLH) domain (also known as pointed domain) located at the N terminus and a DNA-binding domain located at the C terminus. The HLH domain is involved in protein–protein interaction with itself and other members of the ETS family of transcription factors such as FLI1. TEL is a transcription factor, and we and others have shown that it is a repressor of gene expression. To understand further the role of TEL in the cell, we have used an in vivo interaction system to identify proteins that interact with TEL. We show that a protein, UBC9, interacts specifically with TEL in vitro and in vivo. UBC9 is a member of the family of ubiquitin-conjugating enzymes. These enzymes usually are involved in proteosome-mediated degradation; however, our data suggest that interaction of TEL with UBC9 does not lead to TEL degradation. Our studies show that UBC9 binds to TEL exclusively through the HLH domain of TEL. We also show that TEL expressed as fusion to the DNA-binding domain of Gal4 completely represses a Gal4-responsive promoter, but that the coexpression of UBC9 in the same system restores the activity of the promoter. Targeted point mutation of conserved amino acids in UBC9 essential for enzymatic ubiquitination of proteins does not affect interaction nor transcriptional activity. Based on our data, we conclude that UBC9 physically interacts with TEL through the HLH domain and that the interaction leads to modulation of the transcription activity of TEL. PMID:10377438

Cell Type-Specific Modulation of Cobalamin Uptake by Bovine Serum

PubMed Central

Zhao, Hua; Ruberu, Kalani; Li, Hongyun; Garner, Brett

2016-01-01

Tracking cellular 57Co-labelled cobalamin (57Co-Cbl) uptake is a well-established method for studying Cbl homeostasis. Previous studies established that bovine serum is not generally permissive for cellular Cbl uptake when used as a supplement in cell culture medium, whereas supplementation with human serum promotes cellular Cbl uptake. The underlying reasons for these differences are not fully defined. In the current study we address this question. We extend earlier observations by showing that fetal calf serum inhibits cellular 57Co-Cbl uptake by HT1080 cells (a fibrosarcoma-derived fibroblast cell line). Furthermore, we discovered that a simple heat-treatment protocol (95°C for 10 min) ameliorates this inhibitory activity for HT1080 cell 57Co-Cbl uptake. We provide evidence that the very high level of haptocorrin in bovine serum (as compared to human serum) is responsible for this inhibitory activity. We suggest that bovine haptocorrin competes with cell-derived transcobalamin for Cbl binding, and that cellular Cbl uptake may be minimised in the presence of large amounts of bovine haptocorrin that are present under routine in vitro cell culture conditions. In experiments conducted with AG01518 cells (a neonatal foreskin-derived fibroblast cell line), overall cellular 57Co-Cbl uptake was 86% lower than for HT1080 cells, cellular TC production was below levels detectable by western blotting, and heat treatment of fetal calf serum resulted in only a modest increase in cellular 57Co-Cbl uptake. We recommend a careful assessment of cell culture protocols should be conducted in order to determine the potential benefits that heat-treated bovine serum may provide for in vitro studies of mammalian cell lines. PMID:27893837

NHERF Links the N-Cadherin/Catenin Complex to the Platelet-derived Growth Factor Receptor to Modulate the Actin Cytoskeleton and Regulate Cell Motility

PubMed Central

Theisen, Christopher S.; Wahl, James K.; Johnson, Keith R.

2007-01-01

Using phage display, we identified Na+/H+ exchanger regulatory factor (NHERF)-2 as a novel binding partner for the cadherin-associated protein, β-catenin. We showed that the second of two PSD-95/Dlg/ZO-1 (PDZ) domains of NHERF interacts with a PDZ-binding motif at the very carboxy terminus of β-catenin. N-cadherin expression has been shown to induce motility in a number of cell types. The first PDZ domain of NHERF is known to bind platelet-derived growth factor-receptor β (PDGF-Rβ), and the interaction of PDGF-Rβ with NHERF leads to enhanced cell spreading and motility. Here we show that β-catenin and N-cadherin are in a complex with NHERF and PDGF-Rβ at membrane ruffles in the highly invasive fibrosarcoma cell line HT1080. Using a stable short hairpin RNA system, we showed that HT1080 cells knocked down for either N-cadherin or NHERF had impaired ability to migrate into the wounded area in a scratch assay, similar to cells treated with a PDGF-R kinase inhibitor. Cells expressing a mutant NHERF that is unable to associate with β-catenin had increased stress fibers, reduced lamellipodia, and impaired cell migration. Using HeLa cells, which express little to no PDGF-R, we introduced PDGF-Rβ and showed that it coimmunoprecipitates with N-cadherin and that PDGF-dependent cell migration was reduced in these cells when we knocked-down expression of N-cadherin or NHERF. These studies implicate N-cadherin and β-catenin in cell migration via PDGF-R–mediated signaling through the scaffolding molecule NHERF. PMID:17229887

Tumoricidal responses in spontaneous canine neoplasms after extracorporeal perfusion over immobilized protein A.

PubMed

Terman, D S

1981-01-01

I describe morphologic, histologic, immunohistochemical, and serologic changes in dogs with spontaneous breast adenocarcinoma, squamous cell carcinoma, hemangiopericytoma, and fibrosarcoma after extracorporeal perfusion of plasma over heat-killed and formalin-stabilized Staphylococcus aureus Cowans I (SAC), which was embedded in a membrane filtration system. In 12 dogs with breast adenocarcinoma, tumor necrosis was observed within 12 hours after perfusion; 24 hours after perfusion, multiple visible lesions in 6 of 6 dogs exhibited necrosis, but there was no reaction in uninvolved normal mammary tissue. In 8 dogs, healing of large ulcerated areas of cutaneous tumor was observed within 8 to 18 days after perfusion. Similar tumoricidal responses were observed in dogs with other neoplasms after SAC perfusion. Tumor cell necrosis oserved within 4 hours after extracorporeal perfusion was associated with immunohistochemical deposits of IgG and C'3 and ultrastructural evidence of lytic lesions on tumor cell membranes. No tumoricidal effects were observed after perfusion over Staphylococcus aureus Woods (SAW) (non-protein A bearing) in 3 dogs that previously or subsequently responded to SAC perfusion. No tumoricidal reactions were noted after phlebotomy of up to 50% of plasma volume in 6 tumor-bearing dogs that subsequently responded to SAC perfusion. SAC but not SAW perfusion was followed by increases in circulating tumor associated antibodies (TAA) for up to 48 hours after perfusion. Immune complexes increased after perfusion and remained elevated fo 72 hours. Findings suggest that the acute tumoricial responses are not due to mere removal of circulating immune reactants and may be initiated by TAA that are rendered operational after extracorporeal perfusion over SAC. The rapidity, specificity, and magnitude of the observed tumoricidal effects in various canine neoplastic diseases suggests that this may have potentially broad-based therapeutic and biologic implications for canine neoplasia.

A feasibility study to calculate unshielded fetal doses to pregnant patients in 6-MV photon treatments using Monte Carlo methods and anatomically realistic phantoms

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bednarz, Bryan; Xu, X. George

2008-07-15

A Monte Carlo-based procedure to assess fetal doses from 6-MV external photon beam radiation treatments has been developed to improve upon existing techniques that are based on AAPM Task Group Report 36 published in 1995 [M. Stovall et al., Med. Phys. 22, 63-82 (1995)]. Anatomically realistic models of the pregnant patient representing 3-, 6-, and 9-month gestational stages were implemented into the MCNPX code together with a detailed accelerator model that is capable of simulating scattered and leakage radiation from the accelerator head. Absorbed doses to the fetus were calculated for six different treatment plans for sites above the fetusmore » and one treatment plan for fibrosarcoma in the knee. For treatment plans above the fetus, the fetal doses tended to increase with increasing stage of gestation. This was due to the decrease in distance between the fetal body and field edge with increasing stage of gestation. For the treatment field below the fetus, the absorbed doses tended to decrease with increasing gestational stage of the pregnant patient, due to the increasing size of the fetus and relative constant distance between the field edge and fetal body for each stage. The absorbed doses to the fetus for all treatment plans ranged from a maximum of 30.9 cGy to the 9-month fetus to 1.53 cGy to the 3-month fetus. The study demonstrates the feasibility to accurately determine the absorbed organ doses in the mother and fetus as part of the treatment planning and eventually in risk management.« less

Bayesian pretest probability estimation for primary malignant bone tumors based on the Surveillance, Epidemiology and End Results Program (SEER) database.

PubMed

Benndorf, Matthias; Neubauer, Jakob; Langer, Mathias; Kotter, Elmar

2017-03-01

In the diagnostic process of primary bone tumors, patient age, tumor localization and to a lesser extent sex affect the differential diagnosis. We therefore aim to develop a pretest probability calculator for primary malignant bone tumors based on population data taking these variables into account. We access the SEER (Surveillance, Epidemiology and End Results Program of the National Cancer Institute, 2015 release) database and analyze data of all primary malignant bone tumors diagnosed between 1973 and 2012. We record age at diagnosis, tumor localization according to the International Classification of Diseases (ICD-O-3) and sex. We take relative probability of the single tumor entity as a surrogate parameter for unadjusted pretest probability. We build a probabilistic (naïve Bayes) classifier to calculate pretest probabilities adjusted for age, tumor localization and sex. We analyze data from 12,931 patients (647 chondroblastic osteosarcomas, 3659 chondrosarcomas, 1080 chordomas, 185 dedifferentiated chondrosarcomas, 2006 Ewing's sarcomas, 281 fibroblastic osteosarcomas, 129 fibrosarcomas, 291 fibrous malignant histiocytomas, 289 malignant giant cell tumors, 238 myxoid chondrosarcomas, 3730 osteosarcomas, 252 parosteal osteosarcomas, 144 telangiectatic osteosarcomas). We make our probability calculator accessible at http://ebm-radiology.com/bayesbone/index.html . We provide exhaustive tables for age and localization data. Results from tenfold cross-validation show that in 79.8 % of cases the pretest probability is correctly raised. Our approach employs population data to calculate relative pretest probabilities for primary malignant bone tumors. The calculator is not diagnostic in nature. However, resulting probabilities might serve as an initial evaluation of probabilities of tumors on the differential diagnosis list.