3‐(1H‐Indol‐3‐yl)‐1H‐pyrazol‐5‐amine 3 was prepared in a quantitative yield by heating 3‐(1H‐indol‐3‐yl)‐3‐oxopropanenitrile 2 in dry ethanol with hydrazine hydrate, and utilized as key intermediate for the synthesis of some new pyrazolo[1,5‐a]pyrimidines and pyrazolo[5,1‐c]triazines. Structures of the newly synthesized compounds were established by elemental analysis and spectral data and evaluated as antioxidant agents. Most of the tested compounds belonging to the pyrazolo[1,5‐a]pyrimidine series exhibited better activities than members of the pyrazolotriazine one.

In this work, enaminones 1 a,b were used as precursors for the synthesis of novel fused heterocyclic ring systems (e. g. pyrazolo [3,4-d]pyrimidinones, isoxazolo[5,4-d]pyrimidinones, pyrimido [4,5-d]pyrimidinones and related compounds) via their reactions with some N-nucleophiles. The cytotoxic activity of the designed products was assessed via the MTT colorimetric assay against human liver hepatocellular carcinoma (HepG2) and normal lung fibroblasts (WI-38) cell lines using doxorubicin as a reference standard. Among the screened compounds, pyrazolo[3,4-d]pyrimidinone 3 d and pyrimido [4,5-d] pyrimidinones 6 a,b, 7 b and 8 a,b were selected as lead molecules because they showed significant activity against HepG2 cells and a weak cytotoxic effect against WI-38 cells. In further, all of the compounds were subjected to the bleomycin-dependent DNA damage studies. The results indicated that most of them have a remarkable ability to protect DNA compared to ascorbic acid as a standard compound.

Wilms’ tumor, the most prevalent renal tumor in children, is known for its aggressive prognosis and recurrence. Treatment of Wilms’ tumor is multimodal, including surgery, chemotherapy, and occasionally, radiation therapy. Preoperative chemotherapy is used routinely in European studies and in select indications in North American trials. The objective of this study was to build a novel computer-aided prediction system for preoperative chemotherapy response in Wilms’ tumors. A total of 63 patients (age range: 6 months–14 years) were included in this study, after receiving their guardians’ informed consent. We incorporated contrast-enhanced computed tomography imaging to extract the texture, shape, and functionality-based features from Wilms’ tumors before chemotherapy. The proposed system consists of six steps: (i) delineate the tumors’ images across the three contrast phases; (ii) characterize the texture of the tumors using first- and second-order textural features; (iii) extract the shape features by applying a parametric spherical harmonics model, sphericity, and elongation; (iv) capture the intensity changes across the contrast phases to describe the tumors’ functionality; (v) apply features fusion based on the extracted features; and (vi) determine the final prediction as responsive or non-responsive via a tuned support vector machine classifier. The system achieved an overall accuracy of 95.24%, with 95.65% sensitivity and 94.12% specificity. Using the support vector machine along with the integrated features led to superior results compared with other classification models. This study integrates novel imaging markers with a machine learning classification model to make early predictions about how a Wilms’ tumor will respond to preoperative chemotherapy. This can lead to personalized management plans for Wilms’ tumors.

Purpose Higher levels of serum 25-hydroxyvitamin D 25(OHD) are associated with better prognosis in breast and colorectal cancer. However, the evidence is still inconclusive for bladder cancer (BC). Herein, we investigated the diagnosis and prognosis roles of serum levels of 25(OHD) in suspected BC patients presented by hematuria. Methods This prospective cohort study involved suspected patients of BC presented with hematuria. Patients were evaluated by CT urogram, office cystoscopy and urine cytology with subsequent inpatient biopsy for positive findings. Baseline blood samples were collected for measurement of 25(OHD) by electrochemiluminescence binding assay at the time of diagnosis. Patients with non-muscle-invasive BC (NMIBC) underwent transurethral resection of bladder tumor (TURBT) and adjuvant intravesical chemotherapy or BCG instillation. Patients were followed up for their recurrence status during 10 to 24 months. Recurrence was defined as the first time of NMIBC pathological relapse during the follow up period. Results A total of 115 patients were included in the final analysis. Patients had proven pathological BC (64 with NMIBC, and 20 with muscle invasive) and 31 patients were considered as control group. Controls were those patients with BC-free workup (including cytology, cystoscopy, and upper tract imaging). BC group showed a lower level of 25(OHD) than control group 16.47±5.88 versus 28.99±3.19 ng/mL (p<0.001). In addition, muscle invasive group also showed a lower level than NMIBC group 13.17±4.5 versus 17.49±5.04 ng/mL (P = 0.003). During the follow-up period of, tumor recurrence occurred in 16 (25%) of NMIBC patients. The baseline 25(OHD) were decreased in patients who experienced early recurrence; without being statistically significant (15.99 ± 5.17 vs. 18.38 ± 5.14 ng/mL; p = 0.08). 25(OHD) deficiency/insufficiency occurred in 5 (16.1%) and 64 (76.2%) in control and BC patients, respectively, (odds-ratios (OR): 2.13; 95% confidence intervals (CI), 1.52–2.99; P < 0.0001). Conclusion Serum 25(OHD) is significantly decreased in BC patients especially those with tumor muscle invasive group. However, the baseline serum 25(OHD) does not predict the recurrence in the NMIBC patients.

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