PURPOSERecent studies have suggested microscopic positive resection margin should be revised according to the presence of tumor cells within 1mm of the margin surface in resected specimens of pancreatic cancer. However, the clinical meaning of this revised margin status for R1 resection margin was not fully clarified.METHODSFrom July 2012 to December 2014, the medical records of 194 consecutive patients who underwent pancreaticoduodenectomy for ductal adenocarcinoma of the pancreatic head were analyzed retrospectively. They were divided into 3 groups on margin status; revised microscopic negative margin (rR0) - tumor exists more than 1 mm from surgical margin, revised microscopic positive margin (rR1) - tumor present within less than 1 mm from surgical margin, classic microscopic positive margin (cR1) - tumor is exposed to surgical margin.RESULTSThere were 76 rR0 (39.2%), 100 rR1 (51.5%), and 18 cR1 (9.3%). There was significant difference in disease-free survival rates between cR1 vs. rR1 (8.4 months vs. 24.0 months, P = 0.013). Margin status correlated with local recurrence rate (17.1% in rR0, 26.0% in rR1, and 44.4% in cR1, P = 0.048). There is significant difference in recurrence at tumor bed (11.8% in rR0 vs. 23.0 in rR1, P = 0.050). Of rR1, adjuvant treatment was found to be an independent risk factor for local recurrence (hazard ratio, 0.297; 95% confidence interval, 0.127-0.693, P = 0.005).CONCLUSIONRevised R1 resection margin (rR1) affects recurrence at the tumor bed. Adjuvant treatment significantly reduced local recurrence of rR1. Accordingly, adjuvant chemoradiation for rR1 group should be taken into account.

01 Dec 2017·Memórias do Instituto Oswaldo CruzQ4 · MEDICINE

Parenteral adjuvant potential of recombinant B subunit of Escherichia coli heat-labile enterotoxin

Q4 · MEDICINE

ArticleOA

Author: Finger, Paula Fonseca ; Dellagostin, Odir Antônio ; Conceição, Fabricio Rochedo ; Cunha, Carlos Eduardo Pouey da ; Moreira, Ângela Nunes ; Magalhães, Carolina Georg ; Ferreira, Marcos Roberto Alves ; Rocha, Andréa da Silva Ramos ; Moreira Junior, Clóvis

BACKGROUNDThe B subunit of Escherichia coli heat-labile enterotoxin (LTB) is a potent mucosal immune adjuvant. However, there is little information about LTB's potential as a parenteral adjuvant.OBJECTIVESWe aimed at evaluating and better understanding rLTB's potential as a parenteral adjuvant using the fused R1 repeat of Mycoplasma hyopneumoniae P97 adhesin as an antigen to characterise the humoral immune response induced by this construct and comparing it to that generated when aluminium hydroxide is used as adjuvant instead.METHODSBALB/c mice were immunised intraperitoneally with either rLTBR1 or recombinant R1 adsorbed onto aluminium hydroxide. The levels of systemic anti-rR1 antibodies (total Ig, IgG1, IgG2a, and IgA) were assessed by enzyme-linked immunosorbent assay (ELISA). The ratio of IgG1 and IgG2a was used to characterise a Th1, Th2, or mixed Th1/Th2 immune response.FINDINGSWestern blot confirmed rR1, either alone or fused to LTB, remained antigenic; anti-cholera toxin ELISA confirmed that LTB retained its activity when expressed in a heterologous system. Mice immunised with the rLTBR1 fusion protein produced approximately twice as much anti-rR1 immunoglobulins as mice vaccinated with rR1 adsorbed onto aluminium hydroxide. Animals vaccinated with either rLTBR1 or rR1 adsorbed onto aluminium hydroxide presented a mixed Th1/Th2 immune response. We speculate this might be a result of rR1 immune modulation rather than adjuvant modulation. Mice immunised with rLTBR1 produced approximately 1.5-fold more serum IgA than animals immunised with rR1 and aluminium hydroxide.MAIN CONCLUSIONSThe results suggest that rLTB is a more powerful parenteral adjuvant than aluminium hydroxide when administered intraperitoneally as it induced higher antibody titres. Therefore, we recommend that rLTB be considered an alternative adjuvant, even if different administration routes are employed.

01 Nov 2014·Bulletin of Experimental Biology and MedicineQ4 · MEDICINE

Molecular Aspects of Anti-Atherosclerotic Effects of Short Peptides

Q4 · MEDICINE

Article

Author: N. S. Lin’kova ; E. V. Evlashkina ; O. E. Gutop ; A. O. Durnova ; K. L. Kozlov ; V. Kh. Khavinson

We studied molecular mechanisms of the vasoprotective effects of tripeptide T-38 and dipeptide RR-1. Short peptides T-38 and the RR-1 activate the processes of cell renewal in organotypic and dissociated cultures of vascular cells during aging by increasing the expression of Ki-67 and reducing the synthesis of p53 protein. T-38 and RR-1 reduce the synthesis of E-selectin, adhesion molecule involved in the formation of atherosclerotic plaques.

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Indication	Highest Phase	Country/Location	Organization	Date
Neoplasms	Phase 2	US	Dharma Biomedical	-
Immune System Diseases	Preclinical	US	Dharma Biomedical	-

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