Epidemiology of Pancreatic Cancer in Puerto Rico (1987-2010): Incidence, Mortality and Survival.

BACKGROUND & OBJECTIVE: Pancreatic cancer is an uncommon type of cancer worldwide. Nonetheless, even with early diagnosis, mortality rates are high. This study aims to perform an epidemiologic profile of pancreatic cancer in Puerto Rico (PR) from 1987-2010. METHODS: Using data from the Puerto Rico Central Cancer Registry, age-standardized incidence and mortality rates of pancreatic cancer in PR were compared with Hispanics, non-Hispanic Whites, and non-Hispanic Blacks in the United States of America (USA). Incidence and mortality trends of pancreatic cancer were estimated, and survival analyses were also performed. RESULTS: In 2005-2010, 5.8 per 100,000 persons were diagnosed with pancreatic cancer in PR and mortality rates were similar. Pancreatic cancer was more frequent in men (6.5 per 100,000 men) than women (5.2 per 100,000 women), and in persons older than 65 years (32.0 per 100,000 persons). Moreover, the median survival for the people diagnosed with pancreatic cancer in PR during 2006-2007 was 4 months and at the end of the third year after diagnosis, only 13% of the patients survived. Incidence trends of pancreatic cancer showed an increase for men (APC=13.0%, p<0.05) from 2006 to 2010, but not for women (APC=-0.4, p>0.05). However, mortality trends showed a slight decrease for men (APC=-1.0%, p<0.05), but not for women (APC=1.4, p>0.05) in the period of 1987 to 2010. Meanwhile, Puerto Ricans in comparison to other racial/ethnic groups living in the USA showed a lower risk for being diagnosed and of dying from pancreatic cancer. CONCLUSION: Our results highlight the need for additional research in pancreatic cancer, in order to have an impact in disease survival in PR.

GVHD prophylaxis with sirolimus-tacrolimus may overcome the deleterious effect on survival of HLA mismatch after reduced-intensity conditioning allo-SCT.

Large studies, mostly based on series of patients receiving CSA/tacrolimus (TKR) plus MTX as immunoprophylaxis, have demonstrated a deleterious effect on survival of the presence of a single mismatch out of eight loci after allogeneic hematopoietic SCT (alloHSCT). We retrospectively analyzed a series of 159 adult patients who received sirolimus(SRL)/TKR prophylaxis after alloHSCT. We compared overall outcomes according to HLA compatibility in A, B, C and DRB1 loci at the allele level: 7/8 (n=20) vs 8/8 (n=139). Donor type was unrelated in 95% vs 70% among 7/8 vs 8/8 pairs, respectively (P=0.01). No significant differences were observed in 3-year OS (68 vs 62%), 3-year EFS (53 vs 49%) and 1-year non-relapse mortality (9 vs 13%). Cumulative incidence of grades II-IV acute GVHD (aGVHD) was significantly higher in 7/8 alloHSCT (68% vs 42%, P<0.001) but no significant differences were found for III-IV aGVHD (4.5% vs 11%), overall (35% vs 53%) and extensive (20% vs 35%) chronic GHVD in 7/8 vs 8/8 subgroups, respectively. In summary, the present study indicates favorable outcomes after alloHSCT using the combination of SRL/TKR combination as GVHD prophylaxis with OS in the range of 55-70%, and non-significant differences in overall outcomes, irrespective of the presence of any mismatches at obligatory loci.

The roles of the glycosylphosphatidylinositol anchor on the production and immunogenicity of recombinant ookinete surface antigen Pbs21 of Plasmodium berghei when prepared in a baculovirus expression system.

Malarial ookinetes express an immunodominant surface protein (P28) that is a priority candidate for the development of transmission-blocking vaccines. The full length P28 gene from Plasmodium berghei [Pbs21(1-213)] and a deletion construct [Pbs21(1-188)] encoding a protein that lacks the 25 C-terminal amino acids, including the glycosylphosphatidylinositol (GPI) anchor signal, were expressed in insect cells using baculovirus vectors. Pbs21(1-213) protein is strongly hydrophobic, found in the cytoplasm and on the surface of Spodoptera Sf21 cells, and in the culture medium. Pbs21(1-188) protein was largely found in the aqueous phase of the medium and in the cytoplasm of Sf21 cells, but was not detected on the cell surface. The presence of 25 C-terminal amino acids is therefore critical to the attachment of recombinant Pbs21 to the parasite plasma membrane. Mice were immunized subcutaneously or intramuscularly with affinity purified recombinant Pbs21(1-213), Pbs21(1-188) or native Pbs21 proteins. Following two immunizations, native Pbs21 induces higher titres when administered by either route, than the recombinant protein bearing an insect GPI anchor, which in turn is markedly more immunogenic than the recombinant polypeptide lacking a GPI anchor. When specific anti Pbs21 antibody titres exceeded 1 mg/ml all three antigens were capable of inducing transmission blockade > or = 90%, below 1 mg/ml blockade did not correlate with antibody concentration.

Second-generation 1,2,4-benzotriazine 1,4-di-N-oxide bioreductive anti-tumor agents: pharmacology and activity in vitro and in vivo.

SR 4233 (1,2,4-benzotriazine-3-amine 1,4-dioxide) will soon be entering Phase I clinical trials as a new bioreductive cytotoxic agent for the treatment of solid tumors in combination with fractionated radiotherapy. We have selected 3 from over 50 analogues of SR 4233 which showed particular promise as second generation bioreductive antitumor agents. These compounds, when compared to SR 4233, have higher hypoxic toxicity and comparable or higher oxic to hypoxic cytotoxicity ratios in vitro and similar animal toxicity. We have compared the effectiveness of these three compounds with SR 4233 in two tumor systems and have examined some pharmacokinetic properties. The results show that replacement of the amino group at the 3-position of SR 4233 with either a hydrogen or an N,N-dialkylaminoalkylamino group shortens the half-life of these compounds in the blood because of the combined effects of partition coefficients, basicity, and higher reactivity. SR 4754 and SR 4755, the N,N-dialkylaminoalkylamino derivatives, exhibited shorter plasma half-lives than SR 4233 but exhibited lower anti-tumor activity than SR 4233 based on equal mouse toxicity in a fractionated regimen. SR 4482, with the hydrogen substitution and very high electron affinity, possessed a very short blood half life yet retained similar anti-tumor activity as SR 4233.

Factor VIII-associated antigen in human lymphatic endothelium.

Lymphatic vascular endothelium both on tissue section and in culture exhibits positivity for Factor VIII-associated antigen although staining is generally less intense and more spotty than in comparable blood vascular endothelium. Lymphatic endothelium also exhibits Weibel-Palade bodies. Neither marker, therefore, reliably distinguishes blood vascular endothelium from lymphatic endothelium.

Potential antitumor agents. Some sulfur-substituted derivatives of alpha- and beta-2'-deoxythioguanosine.

A series of ten S-substituted derivatives of the alpha and beta anomers (1a and 1b) of 2'-deoxy-6-thioguanosine has been prepared by S-alkylation of the parent nucleosides and/or by mercaptide displacement reactions on 6-chloro intermediates. Against L1210 murine leukemia all beta anomers were active but potency was reduced relative to 1b. Most S-alkyl alpha anomers were inactive in this test. Limited testing against P388 murine leukemia showed all alpha-anomer derivatives to be inactive but the beta anomers were more effective than the parent. S-Substitution sharply reduced acute toxicity in both series. In vitro DNA and RNA synthesis inhibition data are also reported. The antitumor activity of these derivatives and of the 2',5'-di-O-acetyl derivatives of 1a and 1b against lymphoid leukemia L1210 is reported. Some results with the lymphocytic leukemia P388 and an in vitro assay of the inhibition of nucleic acid synthesis are also given.