Papain-Based Vaccination Modulates Schistosoma mansoni Infection-Induced Cytokine Signals.

We have previously shown that immunization of outbred rodents with cysteine peptidases-based vaccine elicited type 2-biased immune responses associated with consistent and reproducible protection against challenge Schistosoma mansoni. We herein start to elucidate the molecular basis of C57BL/6 mouse resistance to S. mansoni following treatment with the cysteine peptidase, papain. We evaluated the early cytokine signals delivered by epidermal, dermal, and draining lymph node cells of naïve, and S. mansoni -infected mice treated 1 day earlier with 0 or 50 µg papain, or immunized twice with papain only (10 µg/mouse), papain-free recombinant S. mansoni glyceraldehyde 3-phosphate dehydrogenase and 2-Cys peroxiredoxin peptide (10 and 15 µg/mouse, respectively = antigen Mix), or papain-adjuvanted antigen Mix. Schistosoma mansoni infection induced epidermal and lymph node cells to release type 1, type 2 and type 17 cytokines, known to counteract each other. Expectedly, humoral immune responses were negligible until patency. Papain pretreatment or papain-based vaccination diminished or shut off S. mansoni infection early induction of type 1, type 17 and type 2 cytokines except for thymic stromal lymphopoietin and programmed the immune system towards a polarized type 2 immune milieu, associated with highly significant (P < 0.005 - <0.0001) resistance to S. mansoni infection.

Neoadjuvant endocrine therapy with or without palbociclib in low-risk patients: a phase III randomized double-blind SAFIA trial.

BACKGROUND: The most prevalent subtype of breast cancer (BC) is luminal hormonal-positive breast cancer. The neoadjuvant chemotherapy regimens have side effects, emphasizing the need to identify new startegies. OBJECTIVE: Analyze the complete pathologic response (pCR) rate and overall response in a low-risk hormone-positive subset of patients receiving neoadjuvant hormone treatment (NAHT) with or without Palbociclib (a CDK4/CDK6 inhibitor) to boost NAHT effectiveness. MATERIALS AND METHODS: Based on the upfront 21-gene Oncotype DX or low-risk Breast Recurrence Score assay (RS™), the SAFIA trial is designed as a prospective multicenter international, double-blind neoadjuvant phase-III trial that selects operable with luminal BC patients that are HER2-negative for the induction hormonal therapy with Fulvestrant 500 mg ± Goserelin (F/G) followed by randomization of responding patients to palbociclib versus placebo. The pCR rate served as the study's main outcome, while the secondary endpoint was a clinical benefit. RESULTS: Of the 354 patients enrolled, 253 initially responded and were randomized to either F/G fulvestrant with palbociclib or placebo. Two hundred twenty-nine were eligible for the evaluation of the pathologic response. No statistically significant changes were observed in the pCR rates for the patients treated with the F/G therapy with placebo or palbociclib (7% versus 2%, respectively) per the Chevallier classification (Class1 + Class2) (p = 0.1464) and 3% versus 10% assessed per Sataloff Classification (TA, NA/NB) (p = 0.3108). Palbociclib did not increase the rate of complete pathological response. CONCLUSION: Neoadjuvant hormonal therapy is feasible in a selected population with a low RS score of < 31 CLINICAL TRIAL: NCT03447132.

The correlation of Helicobacter Pylori with the development of cholelithiasis and cholecystitis: the results of a prospective clinical study in Saudi Arabia.

OBJECTIVE: Gallstone disease is a common surgical ailment. Helicobacter pylori has a role in upper gastrointestinal disorders, including gallstones. This study aimed to determine the association of H. pylori with gallstones, so developing a preventative strategy for gallstone formations. PATIENTS AND METHODS: A prospective study was conducted on 95 patients referred to the surgical clinic of Al-Meeqat General Hospital, Al-Madinah Al-Munawarah, with gallstone disease. Detection of H. pylori antibodies (IgG) in serum was done in all the patients who underwent cholecystectomy. H. pylori stool antigen (HPSA) using stool samples was done for IgG sero-positive patients prior to the cholecystectomy. The bile collected from the gall bladder during operation was examined for the presence of H. pylori by Gram stain, culture and HPSA assay. Gallbladder mucosa was examined for urease A gene by polymerase chain reaction (PCR) in patients proven to be positive for stool or bile serology. RESULTS: Of the 95 patients, 75 (79%) were positive for H. pylori antibodies. Twenty-six (34.7%) patients were positive with H. pylori antigens in bile and 21 (28%) with H. pylori antigens in the stool samples. Among these 47 patients, PCR was positive in 29 (62%) subjects. H. pylori couldn't be detected among the studied patients by using either Gram stain or culture. CONCLUSIONS: The presence of H. pylori in bile may indicate a significant risk for cholelithiasis. PCR is a rapid reliable method for the detection of H. pylori DNA in bile. This rapid molecular approach together with culture and immunological methods could help clinicians to effectively manage patients at high risk of developing gallstones at an earlier stage.

Mammographic breast density: Predictive value for pathological response to neoadjuvant chemotherapy in breast cancer patients.

BACKGROUND: This study aims to evaluate the relation between mammographic breast density (BD) and pathological response to neoadjuvant chemotherapy. METHODS: In this retrospective study, 241 breast cancer patients who received neoadjuvant chemotherapy were included. BD was assessed in mammograms already performed at diagnosis. Pathological complete response (pCR) and pathological stage were correlated with BD, tumour phenotype and other clinico-pathological factors. RESULTS: Patients with low BD had better pCR compared to those with high density (30.5% vs 19.5% respectively, OR = 1.8, 95% CI = 0.98-3.3, p = 0.056) which was more pronounced after adjustment with body mass index (BMI) (OR = 2.4, 95% CI = 1.2-4.8, p = 0.011). HER2-positive disease (32.5% vs. 18.4%, OR = 2.2, 95% = 1.2-4.0, p = 0.01), lower BMI (OR = 1.1, 95% CI = 1.03-1.15, p = 0.004) and lower clinical stage (p = 0.002) were significant predictors of pCR in univariate analysis. In multivariate analysis, low BD (OR = 2.7, 95% CI = 1.3-5.5, p = 0.006) and lower BMI (OR = 1.1, 95% CI = 1.03-1.17, p = 0.003) were independent predictors of better pCR, while early clinical stage (I, II) was of borderline significance (OR = 2.6, 95% CI = 0.99-6.7, p = 0.052). High BD (OR = 1.8, 95% CI = 1.1-3.2, p = 0.03), advanced clinical stage (III) (OR = 1.5, 95% CI = 1.03-2.1, p = 0.03) and higher BMI (OR = 1.06, 95% CI = 1.02-1.11, p = 0.006) were significant predictors of advanced pathological stage. CONCLUSION: Low mammographic BD, low BMI and early clinical stage were associated with improved pCR rate and lower pathological stage after neoadjuvant chemotherapy. BD had more pronounced association with response to chemotherapy after adjustment with BMI.