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Browsing by Author "Pandhiri, Taruni"
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Item Approach to Treatment of Cervical Pregnancy: A Case Report(2022) Campbell, Meredith; Chaudhary, Aysha; Pandhiri, Taruni; Tominack, Hope; Rouse, Caroline E.CASE: A 25yo G1 at 11wk4d dated by LMP and confirmed with a 10 week ultrasound presents with a possible cervical ectopic pregnancy. Past medical, surgical, and OBGYN histories are unremarkable. A cervical pregnancy was suspected on ultrasound due to low implantation of the gestational sac, and a significant posterior bulge with an hourglass shaped uterus. MRI suggested implantation of the placenta in the posterior uterine and cervical wall due to extreme thinning of these structures. Our institution had previously created a protocol for multidisciplinary management of cesarean scar and cervical pregnancies. She desires fertility preservation, and so consented to combined local and systemic treatment with Methotrexate (MTX). Preprocedural Beta-hCG was 81,514.8 mU/mL. Ultrasound-guided transvaginal intra-gestational sac injection of MTX was performed without complication, though cardiac activity was still present at the conclusion of the procedure. The patient also received an IM injection of MTX before discharge. Serial Beta-hCG are still being followed, and are trending towards zero. CONCLUSION: The optimal management for cervical pregnancies is not known, and decisions around type of management are informed by the patient’s desire for fertility preservation. In this case, a protocol created by a multidisciplinary team was used to guide treatment. This protocol using MTX successfully treated the cervical pregnancy at 11wk4d and avoided a surgery that could complicate future fertility. CLINICAL SIGNIFICANCE: Due to the rare occurrence of cervical pregnancy, there is not a universally accepted treatment protocol. This case shows that medical management can be successful for cervical pregnancies. Clear guidelines must be established for cervical pregnancies to optimize outcomes, and decrease maternal morbidity and mortality and to preserve future fertility.Item A Proximal Culture Method to Study Paracrine Signaling Between Cells(MyJove Corporation, 2018-08-28) Dasari, Subramanyam; Pandhiri, Taruni; Haley, James; Lenz, Dean; Mitra, Anirban K.; Medical and Molecular Genetics, School of MedicineIntercellular interactions play an important role in many biological processes, including tumor progression, immune responses, angiogenesis, and development. Paracrine or juxtacrine signaling mediates such interactions. The use of a conditioned medium and coculture studies are the most common methods to discriminate between these two types of interactions. However, the effect of localized high concentrations of secreted factors in the microenvironment during the paracrine interactions is not accurately recapitulated by conditioned medium and, thus, may lead to imprecise conclusions. To overcome this problem, we have devised a proximal culture method to study paracrine signaling. The two cell types are grown on either surface of a 10 µm-thick polycarbonate membrane with 0.4 µm pores. The pores allow the exchange of secreted factors and, at the same time, inhibit juxtacrine signaling. The cells can be collected and lysed at the endpoint to determine the effects of the paracrine signaling. In addition to allowing for localized concentration gradients of secreted factors, this method is amenable to experiments involving prolonged periods of culture, as well as the use of inhibitors. While we use this method to study the interactions between ovarian cancer cells and the mesothelial cells they encounter at the site of metastasis, it can be adapted to any two adherent cell types for researchers to study paracrine signaling in various fields, including tumor microenvironment, immunology, and development.Item Signals from the Metastatic Niche Regulate Early and Advanced Ovarian Cancer Metastasis through miR-4454 Downregulation(AACR, 2020-08) Dasari, Subramanyam; Pandhiri, Taruni; Grassi, Tommaso; Visscher, Daniel W.; Multinu, Francesco; Agarwal, Komal; Mariani, Andrea; Shridhar, Viji; Mitra, Anirban K.; Medical and Molecular Genetics, School of MedicineTreatment of ovarian cancer is limited by extensive metastasis and yet it remains poorly understood. We have studied the critical step of metastatic colonization in the context of the productive interactions with the metastatic microenvironment with a goal of identifying key regulators. By combining miRNA expression analysis using an organotypic 3D culture model of early ovarian cancer metastasis with that of matched primary and metastatic tumors from 42 patients with ovarian cancer, we identified miR-4454 as a key regulator of both early colonization and advanced metastasis in patients with ovarian cancer. miR-4454 was downregulated in the metastasizing ovarian cancer cells through paracrine signals from microenvironmental fibroblasts, which promoted migration, invasion, proliferation, and clonogenic growth in ovarian cancer cells as well as their ability to penetrate through the outer layers of the omentum. Stable overexpression of miR-4454 decreased metastasis in ovarian cancer xenografts. Its mechanism of action was through the upregulation of its targets, secreted protein acidic and cysteine rich (SPARC) and BCL2 associated athanogene 5 (BAG5), which activated focal adhesion kinase (FAK) signaling, promoted mutant p53 gain of function by its stabilization, and inhibited apoptosis. Because microenvironment-induced downregulation of miR-4454 is essential for early and advanced metastasis, targeting it could be a promising therapeutic approach.Item Transcriptome Profiling Reveals Matrisome Alteration as a Key Feature of Ovarian Cancer Progression(MDPI, 2019-10-09) Mitra, Sumegha; Tiwari, Kartikeya; Podicheti, Ram; Pandhiri, Taruni; Rusch, Douglas B.; Bonetto, Andrea; Zhang, Chi; Mitra, Anirban K.; Obstetrics and Gynecology, School of MedicineBACKGROUND: Ovarian cancer is the most lethal gynecologic malignancy. There is a lack of comprehensive investigation of disease initiation and progression, including gene expression changes during early metastatic colonization. METHODS: RNA-sequencing (RNA-seq) was done with matched primary tumors and fallopian tubes (n = 8 pairs) as well as matched metastatic and primary tumors (n = 11 pairs) from ovarian cancer patients. Since these are end point analyses, it was combined with RNA-seq using high-grade serous ovarian cancer cells seeded on an organotypic three-dimensional (3D) culture model of the omentum, mimicking early metastasis. This comprehensive approach revealed key changes in gene expression occurring in ovarian cancer initiation and metastasis, including early metastatic colonization. RESULTS: 2987 genes were significantly deregulated in primary tumors compared to fallopian tubes, 845 genes were differentially expressed in metastasis compared to primary tumors and 304 genes were common to both. An assessment of patient metastasis and 3D omental culture model of early metastatic colonization revealed 144 common genes that were altered during early colonization and remain deregulated even in the fully developed metastasis. Deregulation of the matrisome was a key process in early and late metastasis. CONCLUSION: These findings will help in understanding the key pathways involved in ovarian cancer progression and eventually targeting those pathways for therapeutic interventions.