Adipose Tissue Tumors Research Articles

Conditional MitoTimer reporter mice for assessment of mitochondrial structure, oxidative stress, and mitophagy

Assessment of structural and functional changes of mitochondria is vital for biomedical research as mitochondria are the power plants essential for biological processes and tissue/organ functions. Others and we have developed a novel reporter gene, pMitoTimer, which codes for a redox sensitive mitochondrial targeted protein that switches from green fluorescence protein (GFP) to red fluorescent protein (DsRed) when oxidized. It has been shown in transfected cells, transgenic C. elegans and Drosophila m., as well as somatically transfected adult skeletal muscle that this reporter gene allows quantifiable assessment of mitochondrial structure, oxidative stress, and lysosomal targeting of mitochondria-containing autophagosomes. Here, we generated CAG-CAT-MitoTimer transgenic mice using a transgene containing MitoTimer downstream of LoxP-flanked bacterial chloramphenicol acetyltransferase (CAT) gene with stop codon under the control of the cytomegalovirus (CMV) enhancer fused to the chicken β-actin promoter (CAG). When CAG-CAT-MitoTimer mice were crossbred with various tissue-specific (muscle, adipose tissue, kidney, and pancreatic tumor) or global Cre transgenic mice, the double transgenic offspring showed MitoTimer expression in tissue-specific or global manner. Lastly, we show that hindlimb ischemia-reperfusion caused early, transient increases of mitochondrial oxidative stress, mitochondrial fragmentation and lysosomal targeting of autophagosomes containing mitochondria as well as a later reduction of mitochondrial content in skeletal muscle along with mitochondrial oxidative stress in sciatic nerve. Thus, we have generated conditional MitoTimer mice and provided proof of principle evidence of their utility to simultaneously assess mitochondrial structure, oxidative stress, and mitophagy in vivo in a tissue-specific, controllable fashion.

Resveratrol inhibits obesity-associated adipose tissue dysfunction and tumor growth in a mouse model of postmenopausal claudin-low breast cancer.

Adipose tissue dysregulation, a hallmark of obesity, contributes to a chronic state of low-grade inflammation and is associated with increased risk and progression of several breast cancer subtypes, including claudin-low breast tumors. Unfortunately, mechanistic targets for breaking the links between obesity-associated adipose tissue dysfunction, inflammation, and claudin-low breast cancer growth have not been elucidated. Ovariectomized female C57BL/6 mice were randomized (n = 15/group) to receive a control diet, a diet-induced obesity (DIO) diet, or a DIO + resveratrol (0.5% wt/wt) diet. Mice consumed these diets ad libitum throughout study and after 6 weeks were orthotopically injected with M-Wnt murine mammary tumor cells, a model of estrogen receptor (ER)-negative claudin-low breast cancer. Compared with controls, DIO mice displayed adipose dysregulation and metabolic perturbations including increased mammary adipocyte size, cyclooxygenase-2 (COX-2) expression, inflammatory eicosanoid levels, macrophage infiltration, and prevalence of crown-like structures (CLS). DIO mice (relative to controls) also had increased systemic inflammatory cytokines and decreased adipocyte expression of peroxisome proliferator-activated receptor gamma (PPARγ) and other adipogenesis-regulating genes. Supplementing the DIO diet with resveratrol prevented obesity-associated increases in mammary tumor growth, mammary adipocyte hypertrophy, COX-2 expression, macrophage infiltration, CLS prevalence, and serum cytokines. Resveratrol also offset the obesity-associated downregulation of adipocyte PPARγ and other adipogenesis genes in DIO mice. Our findings suggest that resveratrol may inhibit obesity-associated inflammation and claudin-low breast cancer growth by inhibiting adipocyte hypertrophy and associated adipose tissue dysregulation that typically accompanies obesity.

Intramuscular Hibernoma of the Scapular Region Misdiagnosed on Cytology as a Malignant Lesion: A Report of a Rare Case

Hibernomas are extremely rare benign tumors of adipose tissue characterized by an admixture of brown fat cells with granular, multivacuolated cytoplasm and white fat cells. Hibernomas account for 1.6% of benign adipose tissue tumors and approximately 1.1% of all adipocytic tumors. Around 10% of these cases are intramuscular. It was initially described in the early 1900s as being composed of brown fat. Hibernomas usually occur in third to fourth decades of life and the most frequent sites being thigh, trunk, shoulder, back etc. Cytological differential diagnoses of hibernoma include well differentiated liposarcoma, myxoid/round cell liposarcoma, chondroid lipoma and benign granular cell tumor. Due to its abundant vascularity evident on angiography, it can sometimes mimic a malignant lesion, from which it needs to be distinguished as complete surgical excision is the only treatment required for a hibernoma. Moreover, it has no malignant or metastatic potential. We presented a rare case of intramuscular hibernoma of the scapular region in a 34-year-old male, in which cytology was reported as pleomorphic fibrolipomatous malignant lesion.

Obesity and Breast Cancer: Current Insights on the Role of Fatty Acids and Lipid Metabolism in Promoting Breast Cancer Growth and Progression.

Obesity and excess accumulation of adipose tissue are known risk factors for several types of cancer, including breast cancer. With the incidence of obesity constantly rising worldwide, understanding the molecular details of the interaction between adipose tissue and breast tumors, the most common tumors in women, becomes an urgent task. In terms of lipid metabolism, most of the studies conducted so far focused on upregulated de novo lipid synthesis in cancer cells. More recently, the use of extracellular lipids as source of energy came into focus. Especially in obesity, associated dysfunctional adipose tissue releases increased amounts of fatty acids, but also dietary lipids can be involved in promoting tumor growth and progression. In addition, it was shown that breast cancer cells and adipocytes, which are a major component of the stroma of breast tumors, are able to directly interact with each other. Breast cancer cells and adjacent adipocytes exchange molecules such as growth factors, chemokines, and interleukins in a reciprocal manner. Moreover, it was shown that breast cancer cells can access and utilize fatty acids produced by neighboring adipocytes. Thus adipocytes, and especially hypertrophic adipocytes, can act as providers of lipids, which can be used as a source of energy for fatty acid oxidation and as building blocks for tumor cell growth.

A Rare Case of Refractory Hematemesis Caused by a Gastric Lipoma

Lipomas in the stomach are a rare finding representing less than 1% of all stomach tumors. These are usually asymptomatic and rarely cause significant bleeding or obstructive symptoms. We report an unusual case of a gastric lipoma presenting as massive refractory hematemesis. A 76 year old female taking NSAIDs for a recent hip fracture repair presented with multiple episodes of large volume hematemesis leading to weakness and fatigue. She was initially unstable with hypotension and tachycardia. Her abdominal examination was benign. The patient was intubated for airway protection and resuscitated with blood and intravenous fluids. She had no prior history of gastrointestinal bleeding. The patient underwent an EGD which showed a 3 cm polypoid mass in the posterior gastric body that was actively bleeding. This was cauterized and injected with epinephrine but the patient became hypotensive requiring the case to be stopped. Another EGD was attempted after the patient was transferred to the ICU for stabilization. Endoscopy again showed active bleeding at the mass site and several endoclips were applied and ethanolamine injected for hemostasis. However, bleeding continued with a drop in her hemoglobin and hematocrit to a nadir of 5.9/16.9. Interventional radiology was consulted for embolization. Angiography indicated the bleeding was localized to a branch of the left gastric artery but the vessel could not be accessed due to its tortuosity. The patient was subsequently taken to the operating room given her continued hematemesis. She underwent an open partial gastrectomy removing the stomach body and antrum with retrocolic gastrojejunostomy. Post-surgery, the patient was stable with cessation of bleeding. Anatomical specimens collected from the partial gastrectomy showed a submucosal lipoma measuring 4.5 cm in its greatest dimension with fat necrosis extending into the submucosa and muscularis propria layers. Gastric lipomas are benign tumors of adipose tissue arising from the submucosal layer and rarely present with bleeding or obstructive symptoms. In cases with bleeding the blood loss is usually slow and chronic. Only a few cases of massive bleeding have previously been reported. Endoscopic techniques such as submucosal dissection or unroofing have been employed successfully for treatment of smaller lipomas or those with relatively mild symptoms. However, in the case of larger tumors and those with large volume bleeding surgical resection is usually required.Figure: Initial EGD showing an approximately 3 cm polypoid mass in the posterior gastric body.Figure: The mass seen with EGD shows evidence of active bleeding and an ulcerated tip.Figure: Endoscopic measures failed to achieve hemostasis at the lipoma site.

Sasa veitchii extract reduces obesity-induced insulin resistance and hepatic steatosis in obese mice fed a high-fat diet.

ABSTRACTThe aim of this study was to investigate the therapeutic effect of Sasa veitchii leaf extract (SE) on features of obesity induced by a high-fat diet (HFD), such as hyperglycemia, insulin resistance, and inflammatory response. Four-week-old male ddY mice were freely fed HFD or control normal diet for 12 weeks; half was given SE in addition twice per day in weeks 8–12. Glucose and insulin intolerance were estimated, and body weight measured, weekly throughout the study. Following the experiment, the mice were fasted for 16 h, euthanized, and plasma was collected. Liver and epididymal adipose tissue was collected and weighed. Treatment with SE significantly decreased body weight, adipose tissue weight, plasma glucose, insulin, leptin, and tumor necrosis factor α compared with HFD groups, and markedly reduced the impairment of glucose and insulin tolerance in obese mice. Furthermore, hepatic steatosis and hepatic insulin receptor substrate were improved by treatment with SE. Our findings demonstrate that SE may reduce obesity-induced glucose and insulin tolerance, not only by suppressing inflammatory responses but also by improving insulin signaling.

Co-existence of multiple pyogenic granuloma and intra oral lipoma in a 52 year old female patient- a rare entity

Pyogenic granuloma is a reactive hyperplasia usually arises in the oral cavity secondary to low grade local irritation, traumatic injury, hormonal factors or certain kind of drugs. Lipoma is a benign tumor of adipose tissue, which constitutes 1-4% of all benign lesions. This paper presents the co-existence of pyogenic granuloma and intra oral lipoma on right buccal mucosa, both were managed by surgical intervention.

A case of lipoma in lateral anterior neck: a common entity at an uncommon location

<p>Lipoma is the most common benign mesenchymal tumor of adipose tissue. Their occurrence in head and neck is relatively rare. Lipomas in the neck region are rare tumors that usually present as slowly growing painless masses, found in the lateral portions of the neck. Here, we report a case of lipoma lying over the left lobe of thyroid above the sternal notch in a 41year old man. Swelling was gradually progressive in size since 2 years with no other complaints. Swelling was firm in consistency, mobile, non-tender and not moving with deglutition. It was clinically diagnosed as thyroid neoplasm/ cystic swelling and later on cytological and histopathological examination was performed which revealed benign lipoma. The purpose of this case report is to recognise rare lipomas that occur in unusual locations in the head and neck in order to identify them when they can cause diagnostic problems. </p>

Parosteal ossifying lipoma of the clavicle: A case report.

Lipomas are very common benign adipose tissue tumors that most often develop in subcutaneous tissue. A limited number of studies have described the characteristics of parosteal ossifying lipomas located in the fibula, cervical vertebrae and mandible. However, to the best of our knowledge, parosteal ossifying lipoma of the clavicle has not yet been reported. We herein describe the clinical symptoms, radiological and histological findings in a rare case of parosteal ossifying lipoma of the clavicle in a 40-year-old male patient. The characteristic histological appearance, together with computed tomography and/or magnetic resonance imaging characteristics, should aid in the accurate diagnosis of such cases.

Fibrolipoma of Lip in a Young Individual: A Rare Presentation

ABSTRACTLipomas are tumors of mature adipose tissue. They are commonly seen in the upper extremities, neck, shoulders, and trunk region. However, oral lipomas are relatively rare. They particularly occur in the areas of fat accumulation, especially the cheek, followed by the tongue, floor of the mouth, buccal sulcus and vestibule, lip, palate, and gingiva. Lipomas can be histopathologically classified into classic lipoma and its variant forms, such as fibrolipomas, spindle cell lipomas, intramuscular lipomas, angiolipomas, salivary gland lipomas, pleomorphic lipomas, myxoid lipomas, and atypical lipomas. There have only been a few cases reported on fibrolipoma involving the lower lip in young individuals. Herein, we present a case report on oral fibrolipoma of the lower lip in a 20-year-old female.How to cite this articlePunjabi VH, Patel S, Pathak J, Swain N. Fibrolipoma of Lip in a Young Individual: A Rare Presentation. J Contemp Dent 2017;7(3):181-184.

Giant Intramuscular Lipoma Otot Biceps Brachii

Intramuscular lipoma is a relatively uncommon condition and accounts for just 1,8% of all primary tumors of adipose tissue and less than 1% of all lipoma. This tumor arises within skeletal muscle fibers at various locations. However, giant intramuscular lipomas of biceps brachii muscle are rare tumors.
 A 48-years old man presented with a mass on his right upper-arm. The mass existed for one year and has since increased in size. On physical examination, the mass was pain upon palpation and completely mobile. Plain radiography, the soft tissue mass unremarkable. Computed tomography (CT) scan revealed a hypodense mass situated within right biceps brachii muscle with -72 until -83 Hounsfield. Magnetic resonance imaging (MRI), the mass was found inside of biceps brachii muscle. In T1- and T2- weighted images, the lesion area demonstrated high signal intensity, and SPAIR showed signal suppression similar to normal fat. The patient underwent radical excision of the lesion, which was found to be greater than 12 cm in size. Final pathology revealed intramuscular lipoma.
 A lipoma of greater than 5 cm is classified as a giant lipoma. Giant lipoma in the upper extremities and involving biceps brachii muscle are rare. The plain radiographs may either be unremarkable or may demonstrate a radiolucent soft tissue mass of fat opacity. On CT and MRI, the lipoma appears as an non-invasive mass with homogenous fat signal intensity. The main differential diagnosis of intramuscular lipomas is well-differentiated liposarcomas. The proper management is open excision. The pathological report is vital to confirm the diagnosis.
 We reported a rare case of giant intramuscular lipoma of biceps brachii who was successfully opened excision at our institute. CT scan and MRI can identify and localize these tumours, and facilitate the operative planning

Giant adrenal myelolipoma: A rare case report and review of literature

Myelolipomas are a rare benign variant of adipose tissue tumors with additional hematopoietic elements. In general, these tumors were discovered accidentally on autopsy with a low incidence. Adrenal gland is the most common site for myelolipoma. We reported a case of giant adrenal myelolipoma (>18 cm) which presented with vague, nonspecific pain which is worth mentioning because of its rarity and huge size.

TUMOURS OF OROFACIAL REGION IN ZARIA NIGERIA: A SEVEN YEAR REVIEW

BACKGROUND: Research and literature on orofacial tumours are seldom reported in this part of the world. This study will describe the histopathological features of orofacial tumours seen in a tertiary institution in northern Nigeria. AIMS/OBJECTIVE: To study the pattern of tumours of orofacial region in a tertiary institution in northern Nigeria and compare it with other centres. METHOD: This is a retrospective study in which surgical biopsy specimens seen over 7 year period were reviewed with respect to age, sex, site and histopathological characteristics. RESULTS: Of the 192 lesions of orofacial region that were diagnosed during the study period, there were 24(12.5%) odontogenic and 168(87.5%) of non-odontogenic tumours of which63 (32.8%) were benign and 105 (54.7%) malignant non-odontogenic tumours.The age rangefor odontogenic tumour was 12 year to 54 year, commonly seen in the second decade of life with a male to female ratio of 1.4:1. Ameloblastoma was the most common form 91.7 % .The benign non- odontogenic tumour consist of epithelial (30.2%), vascular tumours (30.2%), bone tumours (23.8%), fibrous and adipose tissue tumours (12.7%)) and neurogenic tumours(3.2%). It is predominantly seen in men with a male to female ratio of 1.25:1. Their ages range from 18 years to 54 years.On the other hand of benign non-odontogenic tumous, Pleomorphic adenoma forms 19.1% Which is the most common.Malignant non-odontogenic tumours are predominantly seen in male with male to female ratio of 1.3:1 and it is commoner in fifth, fourth and third decades of life with age range of12 years to 84 years. Squamous cell carcinoma was the most common malignant non-odontogenic tumourin both males and females and these constitute44.8%. CONCLUSION:Tumours of the orofacial region are diverse and are fairly common. This study have demonstrated that squamous cell carcinoma and ameloblastoma are the most common malignant nonodontogenic and benign odontogenic tumours seen res

The Crosstalk Between Leptin Receptor Activation and iNKT Mediated Anti-Tumor Immunity in Multiple Myeloma

In recent years, researchers have showed a growing interest in the mechanistic relationship between bone marrow adipose tissue and adjacent tumors. However, the impact of bone marrow adipocytes on development of hematological malignancies, particularly multiple myeloma is unknown. With aging, bone marrow changes occur and fatty deposits can occupy up to 70% of the BM cavity. Interactions of bone marrow adipose tissue with bone cells and other immune cells, possibly suggest indirect ways in which bone marrow adipocytes may affect MM disease progression. Leptin, an adipokine released by adipocytes and crucial in energy homeostasis, displays immune modulatory properties but its role in anti-tumor immunity remains unclear. In this study we aimed to investigate the intriguing relationship between leptin receptor activation and invariant natural killer T (iNKT) cell mediated anti-tumor immunity in multiple myeloma. The murine immunocompetent 5T33MM model, mimicking the human disease closely, and human samples of newly diagnosed patients were used to investigate this research topic.A marked increase in serum leptin levels and an upregulation of the leptin receptor expression on iNKT cells was observed in multiple myeloma, in both mice and newly diagnosed patients. In vitro functional analysis demonstrated a direct role for leptin in the downmodulation of the iNKT cell function and an indirect role by acting on the MM cells itself, potentiating the immunosuppressive effect on iNKT cells. We next evaluated the in vivo effects of blocking the leptin receptor together with activating iNKT cells with the prototypic glycolipid a-galactosylceramide (a-GalCer), in the 5T33 myeloma model. Remarkably, strong protection was seen in the combined regimen (a-GalCer and leptin receptor blockade), which was found to be linked to an amplified and sustained activation of iNKT cells, preventing them to become hypoactive. These findings suggest that leptin has a crucial immune suppressive role in myeloma development. Overall, our data reveal the leptin receptor axis as a novel target to treat multiple myeloma. DisclosuresLeleu:TEVA: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria; LeoPharma: Honoraria; Pierre Fabre: Honoraria; Amgen: Honoraria; Bristol-Myers Squibb: Honoraria; Takeda: Honoraria; Celgene: Honoraria; Janssen: Honoraria.

Adipose Tissue Tumor Necrosis Factor-α and Interleukin-6 Response to Glucocorticoid Treatment during Inflammation

The study was performed to examine the actions of glucocorticoids on cytokine (TNF-α and IL-6) concentrations in blood plasma, adipose tissue and cytokines gene expression during acute (streptozotocin, STZ treatment) and chronic inflammation (overweight) in Swiss mice. The experiment was carried out on 6-week-old animals divided into two groups: I - non-obese (fed with a commercial food) and II - overweight mice (fed with a high-fat diet). In each group mice were divided into 4 experimental subgroups: I - control, II - acute inflammation (STZ), III - treated with glucocorticoids (DEX), and IV - STZ with DEX. After injections the animals were decapitated, blood and white adipose tissue (WAT) was quickly removed and directed to measure the plasma levels, tissue concentrations and gene expression of the cytokines (TNF-α, IL-6). Three weeks of treatment with a high-fat diet resulted in increased body weight gain and plasma level of cytokines, whereas did not change TNF-c and IL-6 mRNA gene expression in control animals. STZ, administered once, changed the TNF-α & and IL-6 concentrations in a different manner according to the diet. The TNF-a and IL-6 actions in mice white adipose tissue are down-regulated after glucocorticoids treatment only in overweight animals. The obtained results suggest that glucocorticoids' effects on adipose tissue immune response, both in a pro- and an anti-inflammatory manner, depend on the nutritional status.

The Effects of Mori folium on Insulin Resistance and Adipose Tissue Inflammation in an Experimental Mouse Model of Obesity

Objective: This study was undertaken to investigate the effects of Mori folium on insulin resistance and adipose tissue inflammation in an experimental mouse model of obesity. Methods: Obesity was induced in C57BL/6 mice by feeding them a high-fat diet. The mice were divided into four groups (n=6): a normal diet, high-fat diet, high-fat diet with 40 mg of Mori folium, and high-fat diet with 800 mg of Mori folium groups. After 13 wk, the body weights, fasting blood glucose and fasting serum insulin levels, insulin resistance (homeostatic model assessment) levels, oral glucose tolerance test levels, epididymal fat and liver weights, and gene expression of tumor necrosis factor-α, interleukin-6, and interferon-γ were measured. In addition, adipose tissue macrophages were analyzed by fluorescence- activated cell sorting. Results: Mori folium significantly reduced blood glucose levels, oral glucose tolerance levels, and liver weights. It also reduced adipose tissue macrophage numbers and tumor necrosis factor receptor-α gene expression. Conclusions: These results show that Mori folium has insulin resistance reduction and anti-inflammatory effects in an experimental mouse model of obesity. Keywords: Mori folium, obesity, blood glucose, insulin resistance, anti-inflammatory

Liposarcoma de la órbita

Case reportThe case is presented of a 46-year-old male with right eye proptosis and conjunctival hyperaemia, of 18 months onset. A well-defined intraconal mass was found in the computed tomography. In magnetic resonance this was hypo-intense on T1, enhanced with gadolinium and hyperintense on T2. Excisional biopsy was performed, which was reported as a well-differentiated liposarcoma in the histopathology study. DiscussionLiposarcoma is a malignant adipose tissue tumour. It is very rare in the orbit, with 5 histological types, the most common being myxoid. The treatment of choice is wide surgical excision and may be accompanied with radiotherapy. As it is an infiltrative tumour, It has a high rate of recurrence.

Intraoral spindle-cell lipoma with chondroid differentiation: importance in the diagnosis of oral lesions presenting chondroid tissue

Lipomas are benign neoplasms of adipose tissue presenting several histologic variants, which can be rarely found in the oral cavity. We present a case of a 62-year-old woman with a submucous nodule located in the tongue. Histopathological examination revealed an encapsulated tumor composed of myxoid tissue, spindle cells and mature adipocytes in transition to cartilaginous tissue. The final diagnosis was spindle-cell lipoma with myxoid change and chondroid differentiation. No sign of recurrence was found after five years. The diagnosis of intraoral mesenchymal lesions with chondroid differentiation requires careful histologic examination, mainly to differentiate between benign and malignant lesions.

Colonic lipomas and liposarcomas

Gastrointestinal lipomas are benign rare adipose tissue tumors, most frequently seen in the submucosal layer of the colon. They are often small and asymptomatic, although larger tumors may become symptomatic and pose a diagnostic challenge. Colonoscopy is reliable for the diagnosis of a typical lipoma, but the endoscopic appearances may be worrisome, especially when the lesion is atypical, ulcerated, or bleeding. CT and MRI may reveal the signal and uptake of adipose tissue but a confident diagnosis may not be possible. Histology may be not diagnostic due to the superficial nature of mucosal biopsies. Lipomas can be removed endoscopically, but an increased risk of perforation is associated with polypectomy of larger lesions (Shibata et al., 200826). Surgical intervention is the recommended modality for lipomas more than 4cm in size, lipomas with sessile appearance or involvement of the muscular layer or serosa, unclear preoperative diagnosis, symptomatic lesions, and failed endoscopic removal (Jiang et al., 200715). Segmental resection is the procedure of choice for suspicious lesions. Liposarcoma of the colon is extremely rare and requires the presence of lipoblasts. Only a few cases of primary liposarcoma of the colon have been reported in the literature. The collection of a larger number of cases is needed for the determination of guidelines for the management of this rare tumor.

Intra-oral Lipoma: A Case Report

Lipoma, a benign tumour of adipose tissue, is one of the most common benign neoplasms of the body. However, its occurrence in oral cavity is relatively rare. It accounts for 1 to 4% of benign neoplasms of the oral cavity, affecting predominantly buccal mucosa, floor of mouth and tongue. They have been known to grow to sufficiently large sizes causing problems in mastication and speech. The usual lesion consists of a well-circumscribed, lobulated mass of mature fat cells wherein sometimes, the covering mucosa may become ulcerated presenting difficulty in its diagnosis. Herein, we are presenting a case of intra-oral lipoma affecting right anterior buccal mucosa in a 31 year old female patient. Excisional biopsy was performed and histopathological examination revealed proliferation of mature adipocytes arranged in lobules and separated by numerous fibrous septa. After a 3 month follow-up, the patient did not reveal any signs of recurrence. The clinical and histopathological findings are discussed in detail and literature is reviewed.