Dosing of rapamycin is critical to achieve an optimal antiangiogenic effect against cancer

Rapamycin has antiangiogenic activity against tumors. This has been discussed while addressing the problem of cancer in organ transplantation. Here we investigated effective dosing schedules against tumors and angiogenesis. Growth of established CT-26 colon adenocarcinoma tumors was measured in Balb/c mice treated with total equivalent rapamycin doses (1.5 mg/kg/day) given once a day, once every 3 days, or by continuous infusion. Tumors were most inhibited with continuous rapamycin infusion, and less by bolus dosing. Interestingly, however, continuous dosing produced the lowest rapamycin blood levels (15 ng/ml). As rapamycin-sensitive p70S6-kinase intracellular signaling is critical for angiogenesis, p70S6-kinase activation was measured in endothelial cells by Western blotting. Maximal p70S6-kinase inhibition occurred from 1-5 ng/ml rapamycin. These same rapamycin concentrations optimally blocked vessel-sprouting from cultured aortic rings. Therefore, low-level rapamycin dosing most effectively controls tumors in mice. Importantly, antiangiogenic rapamycin levels are compatible with immunosuppressive doses, supporting its potential use in transplant patients with cancer.     

Extraskeletal Ewing sarcoma of the mesocolon in a child

Ewing sarcoma (ES) is a malignant neoplasm usually affecting the skeletal system. Extraskeletal ES is a rare tumor. To date, only 1 case of primary mesocolon ES has been previously reported in an adult. Herein, we present the first case of ES in the mesocolon in a child.     

Ewing sarcoma of the proximal phalanx: case report

Abstract

We report a case of primary Ewing sarcoma of the proximal phalanx of the right middle finger in an 18-year-old boy. He was treated with neoadjuvant chemotherapy, followed by ray amputation. To restore maximum function, the index ray was transferred to the base of the third metacarpal bone and fixed with a plate. The function of his right hand after the operation was excellent and the cosmetic appearance acceptable. There was no evidence of local recurrence or metastasis after 20 months follow up.     

Primary Ewing sarcoma of the stomach--a newly described entity

The Ewing sarcoma family of tumors (ESFT) includes classic Ewing sarcoma of the bone, extraosseous or soft tissue Ewing sarcoma, Askin tumors of the chest wall, and peripheral primitive neuroectodermal tumors of the bone and soft tissues. They share a common neural histogenesis, tumor genetics and biology. The genetic hallmark of the ESFT is the presence of t(11;22)(q24;q12), which creates the EWS/FLI1 fusion gene and results in the expression of a chimeric protein. Although Ewing tumors can occur at any age, the great majority are found in individuals less than 20 years of age. We herein report a case of gastric Ewing sarcoma in a 68-year-old male. This patient illustrates the second reported occurrence of primary Ewing sarcoma in the stomach and the first reported with the t(11;22)(q24;q12) gene translocation.     

Extraskeletal Ewing sarcoma of the diaphragm presenting with hemothorax

Ewing sarcoma is a relatively uncommon malignant bone neoplasm that usually occurs in children and young adults and involves the major long bones, pelvis, and ribs. Primary diaphragmatic Ewing sarcoma is extremely rare. To the best of our knowledge, only three cases of primary Ewing sarcoma of the diaphragm have been reported. A 12-year-old girl presented spontaneous occurrences of the right hemothorax. After drainage, a roentgenogram film, computed tomography, ultrasonography, and magnetic resonance image showed a giant mass on the right diaphragm. Primary diaphragmatic tumor was resected totally by right posterolateral thoracotomy, and histologically, an extraskeletal Ewing sarcoma was identified. The patient received adjuvant radio-chemotherapy, and there was no evidence of disease 10 months after the operation. Although extremely rare, extraskeletal Ewing sarcoma should be kept in mind in the differential diagnosis of diaphragmatic soft tissue tumors.     

Stable osteosynthesis following ilial resection in intraosseous Ewing sarcoma

A case of a young man with Ewing's sarcoma of the os ilium is demonstrated. The tumor is removed by resection of the os ilium and the adjacent musculature. The bony stability is reconstructed by means of a double autogenous free fibula graft in combination with a broad plate, braced between os sacrum and the roof of the acetabulum. Full weight bearing is possible, at present there is no evidence of a local recidive or of metastases.     

Cyclooxygenase 2 and the kidney

Cyclooxygenase metabolizes arachidonic acid to a family of bioactive fatty acids designated prostaglandins. Two isoforms of cyclooxygenase exist, designated COX1 and COX2. These isoforms are expressed in distinct but important areas of the kidney. COX1 predominates in vascular smooth muscle and collecting ducts, whereas COX2 predominates in the macula densa and nearby cells in the cortical thick ascending limb. COX2 is also highly expressed in medullary interstitial cells. Whereas COX1 expression does not exhibit dynamic regulation, COX2 expression is subject to regulation by several environmental conditions, including salt intake, water intake, medullary tonicity, growth factors, cytokines, and adrenal steroids. Recently, COX2-selective non-steroidal anti-inflammatory drugs have become widely available. Many of the renal effects of non-selective non-steroidal anti-inflammatory drugs (including sodium retention, decreased glomerular filtration rate, and effects on renin-angiotensin levels) appear to be mediated by the inhibition of COX2 rather than COX1. Therefore, in contrast to the gastrointestinal-sparing effects of COX2-selective non-steroidal anti-inflammatory drugs, when considering the kidney, the same caution must be applied when using COX2-selective inhibitors as has been used with traditional non-selective non-steroidal anti-inflammatory drugs.     

Ewing sarcoma of the mandibular condyle: multidisciplinary management optimizes outcome

BACKGROUND: Ewing sarcoma (ES) is a rare, primary malignancy of bone that occurs in childhood and early adolescence. Improved methods of diagnosis and treatment have dramatically increased survival over the last 20 years. Treatment mainstays are chemotherapy and surgical tumor resection. ES usually occurs in long bones of the axial skeleton; however, it may rarely arise in facial structures, particularly the mandible. In these cases, resection presents a challenging postsurgical reconstruction. METHODS AND RESULTS: We present the clinical findings and management of a case of ES that developed in the left mandibular condyle of a 15-year-old female. Chemotherapy and segmental mandibulectomy were used to achieve local control. An innovative temporomandibular joint reconstruction was successfully accomplished using a microvascular fibular free flap and conchal cartilage graft. CONCLUSION: Multidisciplinary management in diagnosis, treatment, and restoration of function produced an optimal result that eliminated disease and preserved aesthetics and quality of life.     

Initial symptoms and clinical features in osteosarcoma and Ewing sarcoma

BACKGROUND: The time between the initial symptoms of osteosarcoma and Ewing sarcoma and the correct diagnosis and treatment is long. Over the last two decades, the prognosis for patients with these diseases has dramatically improved due to a new chemotherapy regimen. As a consequence, a limb-sparing operation has become an alternative to amputation. The aim of this study was to establish the initial symptoms and physical signs of osteosarcoma and Ewing sarcoma from the records of the first medical visit and to identify early characteristics of the diseases to shorten the delay to diagnosis. METHODS: A group of patients with osteosarcoma or Ewing sarcoma was identified from the Swedish Cancer Register of patients thirty years old and younger. Records from the first medical visit due to symptoms related to the bone tumor were obtained for 102 patients with osteosarcoma and forty-seven patients with Ewing sarcoma. RESULTS: Pain related to strain was reported by eighty-seven (85 percent) of the patients with osteosarcoma and thirty (64 percent) of those with Ewing sarcoma, but only twenty-one (21 percent) of the patients with osteosarcoma and nine (19 percent) of those with Ewing sarcoma reported pain at night. Forty-eight (47 percent) of the patients with osteosarcoma and twelve (26 percent) of those with Ewing sarcoma related the onset of symptoms to minor trauma occurring around the same time. A palpable mass was noted in forty (39 percent) of the patients with osteosarcoma and sixteen (34 percent) of those with Ewing sarcoma at the first visit, and in most cases the tumor diagnosis was suspected. There was a broad spectrum of misdiagnoses; the most common was tendinitis, which was the initial diagnosis in thirty-two (31 percent) of the patients with osteosarcoma and ten (21 percent) of those with Ewing sarcoma. The doctor's delay (the period from the first medical visit due to the symptoms to the correct diagnosis) was longer for Ewing sarcoma than for osteosarcoma (nineteen weeks and nine weeks, respectively; p < 0.0001). CONCLUSIONS: An initial symptom of both osteosarcoma and Ewing sarcoma was pain, which was intermittent and often related to strain but not frequently felt at night. A history of trauma was common, but the clinical course often diverged from what was expected from trauma. The clinical course of osteosarcoma and particularly of Ewing sarcoma was not steadily progressive but intermittent, which often misled the doctor into believing that the condition was temporary. The most important clinical feature was a palpable mass, which was noted in more than one-third of the patients at the first visit. This finding emphasizes that a thorough physical examination is absolutely necessary.     

腰椎管内原始神经外胚层瘤/尤文肉瘤1例报告

正原始神经外胚层瘤/尤文肉瘤(primitive neuroectodermal tumor/Ewing sarcoma,PNET/EWS)是一种罕见且高度恶性的肿瘤,起源于神经嵴衍生细胞,具有多向分化的功能~([1])。我院2017年收治1例腰椎管内PNET/EWS患者,报告如下。患者女,32岁。因"腰部疼痛伴双下肢麻木1个月"于2017年4月20入院。查体:L4、L5棘突附近叩痛、压痛阳     

Ewing sarcoma of the jejunum: A case report and literature review

BACKGROUNDEwing sarcomas (ESs) are highly aggressive malignancy and are predominant in the long bones of extremities of children and young adults with a slight male predilection and rarely presents at extra skeletal locations.CASE SUMMARYA 55-year-old woman came to our hospital after finding elevated tumor biomarkers during her physical examination. Her enhanced computed tomography scan showed a jejunal mass. The patient underwent laparoscopic enterectomy. The mass was later diagnosed as ES, evidenced by fluorescence in situ hybridization whereby the GLP ES breakpoint region 1 probe was used, showing that more than 10% of the cells showed a red-green-yellow signal proving the breakpoint rearrangement of the ES breakpoint region 1 gene in chromosome 22.CONCLUSIONWe describe a case of localized ES at the jejunum in China based on the literature.     

Ewing sarcoma originated from rib in 3-year-old child--a case report

A 3-year-old girl was admitted to our hospital with a 3-month history of moderate fever, cough and dyspnea. Chest X-ray and C-T scan showed huge mass with high density, occupying right anterior thoracic cavity. Tumor marker including CEA, AFP, NSE in serum and VMA in urine revealed within normal data. Cytological finding obtained by percutaneous fine needle aspiration demonstrated neuroblastoma. 4 days after admission, urgent operation was performed, because of reinforced dyspnea. Huge tumor was successfully dissected, with combined resection of 2nd and 3rd ribs. Pathological diagnosis showed Ewing sarcoma originated from rib. This case is the youngest case of Ewing sarcoma of bone in Japan, and the patient is alive with disease free at the postoperative period of 21 months.