MRI- and PET-Based Assessment of Radiological and Clinical Factors Associated With Cervical Cancer Response to External Beam Radiation Therapy.

Introduction In the era of MRI-guided external beam radiation therapy (EBRT), complete radiological response (CR) is often seen in cervical cancer (CC) with 4-6 weeks of chemotherapy and EBRT. The clinical and radiological factors associated with this observation were investigated in this study. Materials and methods One hundred and twenty-four CC patients treated with concurrent chemotherapy, EBRT, and brachytherapy (BT) from January 2008 to July 2015 were retrospectively screened.

Dosimetric evaluation of Point A and volume-based high-dose-rate plans: a single institution study on adaptive brachytherapy planning for cervical cancer.

Purpose: External beam radiation therapy (EBRT) and brachytherapy (BT) with concurrent cisplatin is the standard of care for locally advanced cervical cancer. The applicability of image-guided adaptive volume-based high-dose-rate (HDR) intracavitary brachytherapy planning is an active area of investigation. In this study, we examined whether volume-based HDR-BT (HDR) plans leads to more conformal plans compared to Point A (HDR)-based plans.

Cyclooxygenase-2-prostaglandin E2-eicosanoid receptor inflammatory axis: a key player in Kaposi's sarcoma-associated herpes virus associated malignancies.

The role of cyclooxygenase-2 (COX-2), its lipid metabolite prostaglandin E2 (PGE2), and Eicosanoid (EP) receptors (EP; 1-4) underlying the proinflammatory mechanistic aspects of Burkitt's lymphoma, nasopharyngeal carcinoma, cervical cancer, prostate cancer, colon cancer, and Kaposi's sarcoma (KS) is an active area of investigation. The tumorigenic potential of COX-2 and PGE2 through EP receptors forms the mechanistic context underlying the chemotherapeutic potential of nonsteroidal anti-inflammatory drugs (NSAIDs). Although role of the COX-2 is described in several viral associated malignancies, the biological significance of the COX-2/PGE2/EP receptor inflammatory axis is extensively studied only in Kaposi's sarcoma-associated herpes virus (KSHV/HHV-8) associated malignancies such as KS, a multifocal endothelial cell tumor and primary effusion lymphoma (PEL), a B cell-proliferative disorder.

Concurrent targeting of eicosanoid receptor 1/eicosanoid receptor 4 receptors and COX-2 induces synergistic apoptosis in Kaposi's sarcoma-associated herpesvirus and Epstein-Barr virus associated non-Hodgkin lymphoma cell lines.

The effective antitumorigenic potential of nonsteroidal anti-inflammatory drugs (NSAIDs) and eicosonoid (EP; EP1-4) receptor antagonists prompted us to test their efficacy in Kaposi's sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV) related lymphomas. Our study demonstrated that (1) EP1-4 receptor protein levels vary among the various non-Hodgkin's lymphoma (NHL) cell lines tested (BCBL-1:KSHV+/EBV-;BC-3: KSHV+/EBV-; Akata/EBV+: KSHV-/EBV+; and JSC-1 cells: KSHV+/EBV + cells); (2) 5.0 μM of EP1 antagonist (SC-51322) had a significant antiproliferative effect on BCBL-1, BC-3, Akata/EBV+, and JSC-1 cells; (3) 50.

Targeting KSHV/HHV-8 latency with COX-2 selective inhibitor nimesulide: a potential chemotherapeutic modality for primary effusion lymphoma.

The significance of inflammation in KSHV biology and tumorigenesis prompted us to examine the role of COX-2 in primary effusion lymphoma (PEL), an aggressive AIDS-linked KSHV-associated non-Hodgkin's lymphoma (NHL) using nimesulide, a well-known COX-2 specific NSAID. We demonstrate that (1) nimesulide is efficacious in inducing proliferation arrest in PEL (KSHV+/EBV-; BCBL-1 and BC-3, KSHV+/EBV+; JSC-1), EBV-infected (KSHV-/EBV+; Raji) and non-infected (KSHV-/EBV-; Akata, Loukes, Ramos, BJAB) high malignancy human Burkitt's lymphoma (BL) as well as KSHV-/EBV+ lymphoblastoid (LCL) cell lines; (2) nimesulide is selectively toxic to KSHV infected endothelial cells (TIVE-LTC) compared to TIVE and primary endothelial cells (HMVEC-d); (3) nimesulide reduced KSHV latent gene expression, disrupted p53-LANA-1 protein complexes, and activated the p53/p21 tumor-suppressor pathway; (4) COX-2 inhibition down-regulated cell survival kinases (p-Akt and p-GSK-3β), an angiogenic factor (VEGF-C), PEL defining genes (syndecan-1, aquaporin-3, and vitamin-D3 receptor) and cell cycle proteins such as cyclins E/A and cdc25C; (5) nimesulide induced sustained cell death and G1 arrest in BCBL-1 cells; (6) nimesulide substantially reduced the colony forming capacity of BCBL-1 cells. Overall, our studies provide a comprehensive molecular framework linking COX-2 with PEL pathogenesis and identify the chemotherapeutic potential of nimesulide in treating PEL.

Characterization of entry and infection of monocytic THP-1 cells by Kaposi's sarcoma associated herpesvirus (KSHV): role of heparan sulfate, DC-SIGN, integrins and signaling.

KSHV effectively binds, enters and establishes infection in THP-1 cells with initial concurrent expression of latent ORF73 and lytic ORF50 genes and subsequent persistence of ORF73. KSHV genome persisted for 30 days and lytic cycle could be activated. KSHV utilized heparan sulfate for binding to THP-1 cells and primary monocytes.

Kaposi's sarcoma associated herpes virus (KSHV) induced COX-2: a key factor in latency, inflammation, angiogenesis, cell survival and invasion.

Kaposi's sarcoma (KS), an enigmatic endothelial cell vascular neoplasm, is characterized by the proliferation of spindle shaped endothelial cells, inflammatory cytokines (ICs), growth factors (GFs) and angiogenic factors. KSHV is etiologically linked to KS and expresses its latent genes in KS lesion endothelial cells. Primary infection of human micro vascular endothelial cells (HMVEC-d) results in the establishment of latent infection and reprogramming of host genes, and cyclooxygenase-2 (COX-2) is one of the highly up-regulated genes.

Kaposi sarcoma-associated herpes virus (KSHV) G protein-coupled receptor (vGPCR) activates the ORF50 lytic switch promoter: a potential positive feedback loop for sustained ORF50 gene expression.

KSHV vGPCR, a lytic cycle associated protein, induces several signaling pathways leading to the activation of various transcription factors and consequently the expression of cellular and viral genes. Though the role of vGPCR in KSHV tumorigenicity has been well studied, its function related to the viral life cycle is poorly understood. Reduction in vGPCR by RNA interference also resulted in the reduction in KSHV lytic switch ORF50 gene and protein expression.

Abnormal micronuclear telomeres lead to an unusual cell cycle checkpoint and defects in Tetrahymena oral morphogenesis.

Telomere mutants have been well studied with respect to telomerase and the role of telomere binding proteins, but they have not been used to explore how a downstream morphogenic event is related to the mutated telomeric DNA. We report that alterations at the telomeres can have profound consequences on organellar morphogenesis. Specifically, a telomerase RNA mutation termed ter1-43AA results in the loss of germ line micronuclear telomeres in the binucleate protozoan Tetrahymena thermophila.