Background: We evaluated the phenotype of sporadic gastric cancer based on HP status and binding of a tumor risk marker monoclonal, Adnab-9. Methods: We compared a familial GC kindred with an ...extremely aggressive phenotype to HP-positive (HP+) and -negative (HP−) sporadic gastric adenocarcinoma (GC) patients in the same community to determine if similar phenotypes exist. This might facilitate gene discovery to understand the pathogenesis of aggressive GC phenotypes, particularly with publications implicating immune-related gene-based signatures, and the development of techniques to gauge the stance of the innate immune system (InImS), such as the FERAD ratio (blood ferritin:fecal Adnab-9 binding OD-background binding). Resection specimens for the sporadic and familial group were stained for HP and examined for intestinal metaplasia (IM) and immunostaining for Adnab-9. Familial kindred specimens were also tested for the E-cadherin mutation and APC (adenomatous polyposis coli). Survival was evaluated. Results: Of 40 GC patients, 25% were HP+ with a greater proportion of intestinal metaplasia (IM) and gastric atrophy than the HP− group. The proband of the familial GC kindred, a 32-year-old mother with fatal GC, was survived by 13-year-old identical twins. Twin #1 was HP− with IM and Twin #2 was HP+. Both twins subsequently died of GC within two years. The twins did not have APC or E-cadherin mutations. The mean overall survival in the HP+ sporadic GC group was 2.47 ± 2.58 years and was 0.57 ± 0.60 years in the HP− group (p = 0.01). Survival in the kindred was 0.22 ± 0.24 years. Adnab-9 labeling was positive in fixed tissues of 50% of non-familial GC patients and in gastric tissue extract from Twin #2. The FERAD ratio was determined separately in six prospectively followed patient groups (n = 458) and was significantly lower in the gastric cancer patients (n = 10) and patients with stomach conditions predisposing them to GC (n = 214), compared to controls (n = 234 patients at increased risk for colorectal cancer but without cancer), suggesting a failure of the InImS. Conclusion: The HP+ sporadic GC group appears to proceed through a sequence of HP infection, IM and atrophy before cancer supervenes, and the HP− phenotype appear to omit this sequence. The familial cases may represent a subset with both features, but the natural history strongly resembles that of the HP− group. Two different paths of carcinogenesis may exist locally for sporadic GC. The InImS may also be implicated in prognosis. Identifying these patients will allow for treatment stratification and early diagnosis to improve GC survival.
Abstract
Population-based serum banks may allow for the early detection of shed markers of common gastrointestinal cancers. Few GI pan-biomarkers are available for serum testing and those that are ...lack specificity and universal sensitivity for colorectal, gastric and pancreatic cancers. The p87 antigen recognized by the Adnab-9 antibody may be an ideal candidate for such a biomarker. It has both diagnostic and prognostic biomarker ability for these GI cancers but its ability to detect the antigen in serum is unknown. Methods: In order to gauge feasibility of serum testing we conducted a literature search to determine the existence of model established serum banks internationally. An indirect Adnab-9 ELISA was performed on a validation set of sera from 20 CRC patients and 10 controls. A known positive stool extract was used as the positive control. Results: Six countries were found to possess serum banks with the numbers of specimens ranging from 1,982 to 2,132,215. Of these 6 countries, age-adjusted mortality from CRC was highest in the Netherlands at 21/100,000, from gastric cancer highest in Japan 35/100,000 and from pancreatic cancer highest in the USA 11/100,000. The validation sera set Australian patient demographics were similar for gender and ethnicity. The controls were significantly younger than the cancer patients (64±10.3 versus 52.2±3.4 years p<0.002) but there was no direct linear correlation between OD450 and age (r2=0.104;p=0.102). Dilution of serum at both 1:1 and 1:3 ratios showed significantly different mean OD450 values between cancer and control patients of 0.076±0.007 (x±STDEV) versus 0.069±0.006 (p<0.025) and 0.083±0.008 versus 0.074±0.004 (p<0.02) respectively. Eighty percent of cancer patients’ serum were positive versus 30% of controls (OR 9.3; CI 1.6-53.2;p<0.015). Signal to noise ratios of the positive control was satisfactory with the lowest OD450 reading at 0.085 obtained at a 1:6,400 dilution with a linear dilution-reaction curve. Conclusions: National serum banks already exist that could allow for graduated targeted screening of a specific disease based on relative mortality rates. The Adnab-9 antibody is a promising candidate for a pan-biomarker based on the outcome of the indirect ELISA. Since sensitivity of Adnab-9 stool binding is lowest for CRC compared to gastric and pancreatic, it is likely that serum testing for the other 2 cancers would yield comparable results. In order to elucidate this further, testing in prospective studies should be undertaken.
Citation Format: Martin Tobi, Douglas Weinstein, Emma Vizgoft, Susanne Pedersen. Anti-adenoma Adnab-9 antibody recognizes a serum GI cancer candidate biomarker. abstract. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3499. doi:10.1158/1538-7445.AM2013-3499
The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery (WCPCCS) will be held in Washington DC, USA, from Saturday, 26 August, 2023 to Friday, 1 September, 2023, inclusive. The Eighth ...World Congress of Pediatric Cardiology and Cardiac Surgery will be the largest and most comprehensive scientific meeting dedicated to paediatric and congenital cardiac care ever held. At the time of the writing of this manuscript,
The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery
has 5,037 registered attendees (and rising) from 117 countries, a truly diverse and international faculty of over 925 individuals from 89 countries, over 2,000 individual abstracts and poster presenters from 101 countries, and a Best Abstract Competition featuring 153 oral abstracts from 34 countries. For information about the Eighth World Congress of Pediatric Cardiology and Cardiac Surgery, please visit the following website: www.WCPCCS2023.org. The purpose of this manuscript is to review the activities related to global health and advocacy that will occur at the Eighth World Congress of Pediatric Cardiology and Cardiac Surgery. Acknowledging the need for urgent change, we wanted to take the opportunity to bring a common voice to the global community and issue the Washington DC WCPCCS Call to Action on Addressing the Global Burden of Pediatric and Congenital Heart Diseases. A copy of this Washington DC WCPCCS Call to Action is provided in the Appendix of this manuscript. This Washington DC WCPCCS Call to Action is an initiative aimed at increasing awareness of the global burden, promoting the development of sustainable care systems, and improving access to high quality and equitable healthcare for children with heart disease as well as adults with congenital heart disease worldwide.
Abstract
Sporadic pancreatic ductal adenocarcinoma (PDA) is a highly lethal cancer and with no proven screening strategies. Adnab-9, a monoclonal antibody to constituents of human colonic adenomas ...has been shown to be prognostic in IPMN and diagnostic in gastric and colorectal cancer or adenomas (CRN). In this study, we retrospectively and prospectively evaluated the diagnostic potential of Adnab-9 in the stool of two distinct PDA populations. Methods: As proof of principle, 249 Chinese patients submitted stool for screening. Retrospectively, 15 patients had PDA and 80 patients without cancer served as controls. Adnab-9 stool reactivity was determined by ELISA. Prospectively, 1132 American CRN screening program patients submitted stool. Six patients developed PDA over five years of follow-up. 11 Patients free of any significant CRN or other cancer but deceased due to other causes, served as controls. An additional four patients with a known family history of PDA also prospectively submitted stool for Adnab-9. Results: The prospective study results are summarized in the Table. Table: Prospective Study Data for Adnab-9 stool antibody as a biomarker of PDA. The pilot study in Chinese PDA patients found that 12 of 15 patients had stool Adnab-9 ELISA positivity compared to 10 of 80 controls (OR 28, CI 6.7-116.8, P<0.0001). 4 of 6 prospective American study PDA patients had either stool ELISA or Western blot positivity for Adnab-9 compared to 1 of 11 controls (OR=20, CI 1.4-287.6, P<0.03). 2 of 4 patients with family history of PDA had stool positive by Adnab-9 ELISA or Western blot. Conclusions: Our study suggests that Adnab-9 stool tests may be an effective PDA diagnostic marker. Based on previous data in CRC and IPMN, Adnab-9 appears to bind Paneth-like cells, which we and others have shown to be cancer-associated and the likely source of the stool antigen. Future prospective studies are needed to confirm the diagnostic efficacy of Adnab-9 stool testing in PDA.
Citation Format: {Authors}. {Abstract title} abstract. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3699. doi:1538-7445.AM2012-3699
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Background: CS is characterized by germline PTEN mutations. Because tumors from CS patients show increased activation of the PI3K/Akt/mTOR pathway, mTOR inhibitor such as S might ...have activity in such patients. Methods: Eligibility: subjects with germline PTEN mutation who meet international diagnostic criteria for CS, age 18, ECOG PS 0-2, and adequate organ function. Subjects were treated with a 56-day course of daily oral S (2 mg). Objective: Inhibition of the mTOR pathway in benign skin/GI lesion, as assessed by IHC (P-AKT, Total S6, P-S6, P-4E-BP1, score 0-4), changes in benign or malignant tumor by CT/MRI/PET, digital dermoscopy/endoscopy, and changes in cerebellar testing by modified SARA (Neurology 2006). Protocol was amended to allow up to 20 subjects. Results: A total of 18 pts/16 families were enrolled. Median age 42 (range 19-69). Male/Female: 9/9. Involvement in skin, thyroid, GI polyps, breast, CNS, and all of the five organs was observed in 18, 15, 13, 8, 18, 5 subjects, respectively. 7 had h/o malignancies: 3 renal cell, 4 breast, 3 thyroid, 4 others. 3 cerebellar gangliocytomas and 2 others were measurable by CT or MRI. PTEN mutations: 6 families in Exon 1-2, 1 in Exon 4, 9 in Exon 5-8. All but one (D24H) were truncating mutations. 11 of 16 pts who completed a 56-day course reported subjective improvement in energy, mood, focus or skin lesion. Pts with Ex6-8 mutation (n=4) had a median SUV decrease of 29.4%. Regression of skin and GI lesions was observed by dermoscopy or endoscopy. Cerebellar evaluation showed a significant improvement in a total SARA score at 1 month (n=9, p=0.034). 3 pts were treated for only 28 days due to voluntary withdrawal. IHC analysis in skin and GI benign lesions showed a decrease in average P-S6K, P-S6, Total S6, P-S6/Total S6 in response to S. P-S6K/Total S6 ratios at d14 and d56 were significantly lower than at baseline (p=0.0026, 0.0391, respectively). The most common AEs (all grades >25%) were LFTs/Hb (39%), fatigue/hypercholesterolemia (28%). Grade 3 AEs: 1 pt hypophosphatemia/lymphopenia. Conclusions: A 56-day course of S was well tolerated in subjects with CS and was associated with improvement in symptoms, skin/GI lesions, cerebellar function and decreased mTOR signaling. Clinical trial information: NCT00971789.
