Differential responses to genotoxic agents between induced pluripotent stem cells and tumor cell lines

Given potential values of induced pluripotent stem (iPS) cells in basic biomedical research and regenerative medicine, it is important to understand how these cells regulate their genome stability in response to environmental toxins and carcinogens. The present study characterized the effect of Cr(VI), a well-known genotoxic agent and environmental carcinogen, on major molecular components of DNA damage response pathways in human iPS cells. We compared the effect of Cr(VI) on human iPS cells with two established cell lines, Tera-1 (teratoma origin) and BEAS-2B (lung epithelial origin). We also studied the effect of hydrogen peroxide and doxorubicin on modulating DNA damage responses in these cell types. We demonstrated that ATM and p53 phosphorylation is differentially regulated in human iPS cells compared with Tera-1 and BEAS-2B cells after exposure to various genotoxic agents. Moreover, we observed that inhibition of CK2, but not p38, promotes phosphorylation of p53S392 in iPS cells. Combined, our data reveal some unique features of DNA damage responses in human iPS cells.

via Journal of Hematology & Oncology

Swallow therapy combats post-radiotherapy dysphagia

Swallowing exercises can help to minimize the risk for dysphagia in patients undergoing radiotherapy for head and neck cancer, a case study suggests.

via Med Wire News

Sarcoidosis lymphoma syndrome - the value of PET-CT in the diagnosis

We report a 52-year-old patient who developed B-cell non-Hodgkin's lymphoma subsequent to sarcoidosis. Sarcoidosis was diagnosed 16 years ago and remained asymptomatic for 14 years after steroid treatment. She presented with new symptoms of arthralgia, photosensitivity, butterfly erythema, autoimmune antibodies (ANA, chromatin positivity) associated with progression of the known left upper lobe lesion on the chest X-ray suggesting primary autoimmune disease (systemic lupus erythematosus). As steroid treatment was not effective, we started bolus cyclophosphamide therapy after which progression was seen on the chest X-ray. Computed tomography (CT)-guided needle biopsy confirmed malignancy of indefinable origin. Despite of the well-known fluorodeoxyglucose (FDG) avidity in active sarcoidosis, a FDG-positron emission tomography (PET) scan was performed to stage the primary tumour. Intensive FDG uptake was detected in the affected lung segment, with moderate uptake in mediastinal lymph nodes. The patient underwent left upper lobectomy. The histology showed pulmonary mucosa-associated lymphoma (bronchus-associated lymphoid tissue (BALT) lymphoma) in the lung tissue, while only sarcoidosis was present in the mediastinal lymph nodes. Bone marrow biopsy was negative.The association between sarcoidosis and lymphoma is known as sarcoidosis lymphoma syndrome, which is a rare disease. PET-CT was helpful in the differentiation of sarcoidosis and malignancy in this patient. It is important to be aware of the risk of lymphoma in sarcoidosis and FDG-PET, used for adequate purpose, can help the diagnosis.

via World Journal of Surgical Oncology

Carcinoma ex pleomorphic adenoma of the upper lip: a case of an unusual malignant component of squamous cell carcinoma

Background: Squamous cell carcinoma (SCC) as the malignant component of carcinoma ex pleomorphic adenoma (CXPA) occurring in upper lip is rare.Case report: A 55-year-old male patient presented with an asymptomatic mass of the upper lip that he had noticed 8 years previously. The mass was clinically suspected to be a benign salivary gland tumor based on palpation and magnetic resonance imaging findings. A needle biopsy was then carried out, and the pathological diagnosis was pleomorphic adenoma. The tumor was removed under general anesthesia. Histopathological examination revealed well-demarcated tumor tissues showing typical histologic features of pleomorphic adenoma. However, SCC tissue with several mitotic figures was found in the central area of the tumor tissue. The tumor was finally diagnosed as CXPA. There was no evidence of recurrence or metastasis 6 years postoperatively. Conclusion: This is the first report of CXPA of the upper lip with an unusual malignant component of SCC.

via World Journal of Surgical Oncology

Neglected synovial osteochondromatosis of the elbow: a rare case

Background: Synovial osteochondromatosis is a benign metaplastic proliferative disorder of the synovium characterised by the formation of multiple cartilaginous nodules in the synovium, many of which detach and become loose bodies. The disease is characteristically monoarticular, most commonly involving the knee. A site in the elbow was first reported in 1918 by Henderson, but any joint may be involved. Very few cases of synovial osteochondromatosis of the elbow have been reported in the literature. The presenting symptoms are usually diffuse discomfort in the affected joint and decreased range of motion with an accompanying gritty or locking sensation. The treatment of choice is excision of the synovium and removal of the loose bodies.Case presentationWe report a rare neglected case covering a 32-year period of a locally aggressive synovial osteochondromatosis of the elbow in a 47-year-old man. Clinical examination revealed a significant increase in size of the left elbow compared to the contralateral one. The simple radiographs and the computed tomography showed multiple rounded, calcified bodies widespread throughout the elbow joint. At surgery we removed and counted a total of 312 loose bodies, varying in size from a few millimeters to 3 cm. The evaluation at 6 months postoperatively showed marked reduction in the volume of the elbow, improvement of extension and flexion and an increase of the Mayo elbow performance score from 50 points before surgery to 80 points at 6 months postoperative. Conclusion: Synovial osteochondromatosis is an uncommon condition characterized by the formation of multiple nodules of hyaline cartilage within the sub-synovial connective tissue. The differential diagnosis includes chronic articular infection, osteoarthritis, pigmented villonodular synovitis, mono-articular inflammatory arthritis and periarticular neoplasms like synovial sarcoma. The treatment of choice is excision of the synovium and removal of the loose bodies. The prognosis is good, but recurrences may occur if the removal is incomplete.

via World Journal of Surgical Oncology

Population level survival of patients with chronic myelocytic leukemia in Germany compared to the US in the early 21st century

IntroductionThe advent of tyrosine kinase inhibitors has produced 5-year survival of 90 + % for chronic myelocytic leukemia (CML) patients in clinical trials. However, population level survival has been lower, especially in older patients. Here, we examine survival of patients with CML in Germany and compare it to survival of patients in the United States (US). Methods: Data were extracted from the Surveillance, Epidemiology, and End Results database in the US and 11 cancer registries in Germany. Patients 15--69 years old diagnosed with CML were included in the analysis. Period analysis for 2002--2006 was used to provide the most up-to-date possible estimates of five-year relative survival. Results: Five-year relative survival was 68.7% overall in Germany and 72.7% in the US. Survival was higher in the US for all age groups except for ages 15--39 years, but the difference was only statistically significant for ages 50--59 years (at 67.5% vs 77.7% in Germany and the US, respectively). Survival decreased with age, ranging from 83.1% and 81.9%, respectively, in Germany and the US for patients 15--39 years old to 54.2% and 54.5%, respectively, in patients 65--69 years old. Survival increased between 2002 and 2006 by 12.0% points in Germany and 17.1% points in the US. Conclusions: Five-year survival estimates were higher in the US than in Germany overall, but the difference was only significant for ages 50--59 years. Survival did not equal that seen in clinical trials for either country, but strong improvement in survival was seen between 2002 and 2006.

via Journal of Hematology & Oncology

Clinical course for patients with peritoneal carcinomatosis excluded from cytoreductive surgery and hyperthermic intraperitoneal chemotherapy

Background: Cytoreductive surgery combined with 'Hyperthermic IntraPEritoneal Chemotherapy' (HIPEC) represents the only potentially curative treatment available for carcinomatosis secondary to colorectal cancer (CRC), pseudomyxoma peritonei (PMP), malignant mesothelioma (MM) and goblet cell carcinoma (GCC). Despite preoperative investigation some patients are excluded perioperatively because of unacceptably massive tumor extent. The data available on the clinical course of these patients are sparse. Methods: This was a retrospective observational study based on records from 35 patients (21 men, 14 women) treated in a national center (Surgical Department P, Aarhus University Hospital) from June 2006 to August 2011. The study population included patients aged 18 to 70 years with CRC (n = 19), PMP (n = 11), MM (n = 3) or GCC (n = 2). Vital status was obtained by 29 November 2012. Three patients were lost to follow-up. Results: The 30-day mortality rate was 0%. Postoperative complications within 30 days occurred in three patients (9.4%). In all, 19 patients (54%) had palliative surgery during exploratory laparotomy. In total, 28 patients (88%) received palliative chemotherapy. The median survival for CRC and PMP patients was 12.7 (95% CI 4.0 to 21.4) and 26.9 (95% CI 25.7 to 28.1) months, respectively. Conclusions: Exploratory laparotomy for intended curative treatment of peritoneal carcinomatosis did not imply major morbidity or mortality for patients excluded from treatment due to advanced stage of disease.

via World Journal of Surgical Oncology