Calcium signaling, in addition to its numerous physiological roles, is also implicated in several pathological conditions including cancer. An increasing body of evidence suggest critical roles of calcium signaling in the promotion of different aspects of cancer, including cell proliferation, therapy resistance and metastatic-related processes. In many cases, this is associated with altered expression and/or activity of some calcium channels and pumps. Brain cancers have also been the subject of many of these studies. In addition to diverse roles of calcium signals in normal brain function, a number of proteins involved in calcium transport are implicated to have specific roles in some brain cancers including gliomas, medulloblastoma, neuroblastoma and meningioma. This review discusses research that has been conducted so far to understand diverse roles of Ca2+-transporting proteins in the progression of brain cancers, as well as any attempts to target these proteins towards a therapeutic approach for the control of brain cancers. Finally, some knowledge gaps in the field that may need to be further considered are also discussed.

Background. Rosai-Dorfman Disease (RDD) is rare benign hematologic disorder of histiocytes, which usually manifests as painless lymphadenopathy, fever, leukocytosis and hypergammaglobulinemia. Extranodal RDD has been reported in 43% of cases, with skin as commonly involved site followed by head and neck region. However, soft tissue cheek mass is rare presentation of extra-nodal RDD. Case Presentation. A 26-year-old Saudi man presented with a six-month history of right cheek swelling and left upper eyelid swelling. Physical examination revealed right cheek mass of size 3 × 3 cm and left upper eyelid mass of size 1 × 2 cm and no palpable cervical lymphadenopathy. Incisional biopsy of cheek mass showed positivity for S100 and negativity for CD1a, consistent with extra-nodal RDD. Patient did not respond to systemic steroids and was given radiation therapy to left orbit with minimal response. Then, he was started on chemotherapy Rituximab, cyclophosphamide, vincristine, and prednisolone (RCVP) 8 cycles followed by reirradiation 10 Gy in 10 fractions with 6 MeV electron with complete response. After 12 months of followup, patient had recurrence in right cheek and was started on radiotherapy to the cheek mass. Conclusion. Extra-nodal RDD with involvement of cheek is a rare presentation. Incorporation of S100 and CD1a is helpful in diagnoses of RDD and differentiating it from other benign histiocytosis. Treatment consists of surgery, steroids, chemotherapy, and radiation therapy.

Objectives:Assess the added value of dual time point F-18-fluorodeoxyglucose positron emission tomography/computed tomography (DTP F-18-FDG-PET/CT) in the differentiation of malignant from a benign lesion in cancer patients.Materials and Methods:Totally, 140 F-18-FDG PET/CT scans of 60 cancer patients who underwent DTP protocol (early whole body PET/CT [E] at 60 min [range, 45–76 min] and delayed limited PET/CT [D] on areas of interest at 120 min [range, 108–153 min] after the tracer injection) were retrospectively reviewed. Visual and semi-quantitative analysis was performed on both early and delayed images. All findings were confirmed by histopathology and/or at least 3 months follow-up (F-18-FDG PET/CT, CT, or magnetic resonance imaging). The result was considered true positive (TP) if delayed standardized uptake value (SUV) of suspicious lesions increased and confirmed to be malignant, false positive (FP) if delayed SUV increased and confirmed to be benign, true negative (TN) if delayed SUV unchanged or decreased and confirmed to be benign, and false negative (FN) if delayed SUV unchanged or decreased and confirmed to be malignant.Results:A total of 164 suspicious lesions were detected (20 presacral lesions, 18 lung nodules, 18 Hodgkin's disease (HD) lesions, 16 rectal lesions, 16 head and neck (H and N) lesions, 14 hepatic lesions, 14 non-Hodgkin's lymphoma (NHL) lesions, 12 mediastinal lymph nodes (LNs), 10 focal gastric uptake, 10 soft tissue lesions, 8 breast lesions, 4 peritoneal nodule, and 4 others). Sixty-four lesions were pathologically confirmed, and 100 lesions were confirmed based on 3–6 months follow-up. There were 62 TP lesions, 44 FP, 58 TN and no FN results. The overall sensitivity was 100% of DTP F-18-FDG PET/CT in detecting suspicious lesions. The specificity was 57% in differentiating malignant from benign lesions, and the accuracy was 73%. Positive predictive value was 59%, negative predictive value (NPV) 100%. All hepatic lesions were TP. Accuracy in metastatic hepatic lesions HD, presacral soft tissue, lung nodules, H, and N cancer, breast cancer, NHL and mediastinal LN was100%, 88.8%, 80%, 78%, 75%, 75%, 71%, and 33.3%, respectively.Conclusions:DTP F-18-FDG-PET/CT protocol does not always work in differentiation between benign and malignant lesions. However; it has high NPV, and promising results was noted in hepatic lesions, lymphoma, and recurrent rectal cancer.

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Medulloblastoma (MB) is the most common malignant childhood brain cancer. High-risk MB tumours have a high incidence of metastasis and result in poor patient survival. Drug screens, commonly used to identify potential novel therapeutic agents against MB, focus on 2D cell proliferation and viability assays given that these assays are easily adaptable to high-throughput regimes. However, 2D models fail to address invasive characteristics that are crucial to MB metastasis and are thus not representative of tumour growth in vivo. In this study, we developed a 3D 384-well agar colony formation assay using MB cells of molecular subgroup 3 that is associated with the highest level of metastasis. Two fluorescence substrates, resazurin and glycyl-phenylalanyl-aminofluorocoumarin (GF-AFC) that measure cell viability via distinct mechanisms were used to assess the growth of MB cells in the agar matrix. The assay was optimised for seeding density, growth period, substrate incubation time and homogeneity of the fluorescent signals within individual wells. Our data demonstrate the feasibility to multiplex the two fluorescent substrates without detectable signal interference. This assay was validated by assessing the concentration-dependent effect of two commonly used chemotherapeutic agents clinically used for MB treatment, vincristine and lomustine. Subsequently, a panel of plasma membrane calcium channel modulators was screened for their effect on the 3D growth of D341 MB cells, which identified modulators of T-type voltage gated and ORAI calcium channels as selective growth modulators. Overall, this 3D assay provides a reproducible, time and cost-effective assay for high-throughput screening to identify potential drugs against MB.