Potential Utility of Cell Free High Mobility Group AT-hook 2 (HMGA2) as a Prognostic Biomarker in Liquid Biopsies of Oral Squamous Cell Carcinoma.

BACKGROUND: Locoregional spread is a frequent finding in oral cancer which dictates poor prognosis. HMGA2 expression has been linked to malignant traits of oral cancer in tissue biopsies however, data on HMGA2 expression in liquid biopsies in oral cancer is sparse. Purpose of this study was to explore prognostic relevance of HMGA2 in liquid biopsies of oral cancer patients. PATIENTS AND METHODS: After obtaining approval from Institutional Review Board of Ziauddin University and informed written consent from study subjects, expression of circulating HMGA2 was evaluated in 96 OSCC cases and 100 age and sex matched controls via real time PCR using specific set of primers. We further analyzed relationship of various sociodemographic and clinicopathological variables with HMGA2expression and explored its prognostic potential. RESULTS: Expression was seen in 22 (23%) cases. A higher expression was observed among subjects with local invasion (52.6% vs 47.4 %), distant metastasis (71.4% vs 28.6%) and tumor recurrence (57.1% vs 42.9%) p.

Intergroup Randomized Phase III Study of Postoperative Oxaliplatin, 5-Fluorouracil, and Leucovorin Versus Oxaliplatin, 5-Fluorouracil, Leucovorin, and Bevacizumab for Patients with Stage II or III Rectal Cancer Receiving Preoperative Chemoradiation: A Trial of the ECOG-ACRIN Research Group (E5204).

BACKGROUND: The addition of bevacizumab to chemotherapy improved outcomes for patients with metastatic colon cancer. E5204 was designed to test whether the addition of bevacizumab to mFOLFOX6, following neoadjuvant chemoradiation and definitive surgery, could improve overall survival (OS) in patients with stage II/III adenocarcinoma of the rectum. SUBJECTS, MATERIALS, AND METHODS: Patients with stage II/III rectal cancer who had completed neoadjuvant 5-fluorouracil-based chemoradiation and had undergone complete resection were enrolled. Patients were randomized to mFOLFOX6 (Arm A) or mFOLFOX6 with bevacizumab (Arm B) administered every 2 weeks for 12 cycles. RESULTS: E5204 registered only 355 patients (17% of planned accrual goal) as it was terminated prematurely owing to poor accrual. At a median follow-up of 72 months, there was no difference in 5-year overall survival (88.3% vs. 83.7%) or 5-year disease-free survival (71.2% vs. 76.5%) between the two arms. The rate of treatment-related grade ≥ 3 adverse events (AEs) was 68.8% on Arm A and 70.7% on Arm B. Arm B had a higher proportion of patients who discontinued therapy early as a result of AEs and patient withdrawal than did Arm A (32.4% vs. 21.5%, p = .029).The most common grade 3-4 treatment-related AEs were neutropenia, leukopenia, neuropathy, diarrhea (without prior colostomy), and fatigue. CONCLUSION: At 17% of its planned accrual, E5204 did not meet its primary endpoint. The addition of bevacizumab to FOLFOX6 in the adjuvant setting did not significantly improve OS in patients with stage II/III rectal cancer. IMPLICATIONS FOR PRACTICE: At 17% of its planned accrual, E5204 was terminated early owing to poor accrual. At a median follow-up of 72 months, there was no significant difference in 5-year overall survival (88.3% vs. 83.7%) or in 5-year disease-free survival (71.2% vs. 76.5%) between the two arms. Despite significant advances in the treatment of rectal cancer, especially in improving local control rates, the risk of distant metastases and the need to further improve quality of life remain a challenge. Strategies combining novel agents with chemoradiation to improve both distant and local control are needed.

Association of visfatin with chronic kidney disease in a cohort of patients with and without diabetes.

OBJECTIVE: To evaluate association of serum visfatin with CKD secondary to diabetic nephropathy and to compare it with patients of CKD secondary to other risk factors. METHODS: Seventy eight individuals including 28 healthy controls and 50 patients of CKD were included in this study. Patients with CKD were further grouped based on etiology of CKD into diabetics and non-diabetics. Patients with type 1 diabetes mellitus, urinary tract infection, urolithiasis, liver cirrhosis, stroke, ischaemic heart disease, and rheumatoid arthritis were excluded. Measurement of Serum visfatin was done through EIA Kit (Phoenix pharmaceuticals Burlingame CA). RESULTS: Visfatin concentration was significantly high in patients with CKD compared to controls (8.7 +/- 4.7 vs. 5.2 +/- 3.3 p = 0.001). No significant difference in Visfatin concentrations between patients of CKD with and without diabetes was detected (9.2 +/- 5.5 vs. 8.3 +/- 3.2 p = 0.694). A significant negative correlation of visfatin with estimated GFR (r2= -0.383, p = 0.01) and a positive correlation with degree of proteinuria (p = 0.01) was observed. CONCLUSION: The present study confirms the association of visfatin with CKD, however further studies at molecular level to check its expression within renal tissue may clarify its definitive role in CKD

Differential sensitivity to imatinib of 2 patients with metastatic sarcoma arising from dermatofibrosarcoma protuberans.

Dermatofibrosarcoma protuberans (DFSP) is a rare superficial sarcoma usually affecting the trunk, with significant risk of local recurrence. It is characterized by the presence of ring chromosomes or chromosomal translocations fusing the promoter of the collagen gene COL1A1 to the platelet-derived growth factor beta-chain gene PDGFB, increasing the production of PDGF locally and promoting autocrine or paracrine tumor growth. Fewer than 5% of patients with DFSP develop metastatic sarcoma, with a poor subsequent prognosis. Imatinib (STI-571) was developed as an inhibitor of the PDGF receptor tyrosine kinase and has proven clinical activity against chronic myelogenous leukemia (expressing bcr-abl) and gastrointestinal stromal tumors (expressing c-kit). We describe 2 patients with metastatic and unresectable metastases from DFSP treated with imatinib. After confirmation of negative CD117 status of 2 sarcomas arising from DFSP, patients were given imatinib 400 mg po qd and assessed at regular intervals for their tolerance and response to therapy. One patient had a transient response, then progressed rapidly and died of disease. Another patient showed a partial response to therapy after 2 months, with resolution of superior vena cava syndrome and shrinking of metastatic lung lesions. His response is ongoing after 6 months of therapy. These clinical data confirm findings from models of DFSP and support the use of imatinib in the rare setting of metastatic DFSP. Imatinib may be useful for patients with locally advanced DFSP, when other options for local therapy are limited.