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To study patients with spinal arachnoid cysts, who underwent cyst excision with dural defect repair or marsupialization, and their outcomes. The retrospective analysis involved reviewing the records of 38 patients who underwent surgical treatment for spinal arachnoid cysts in the Department of Neurosurgery at Christian Medical College, Vellore, between August 2004 and December 2022. The study examined the demographics, clinical presentation, imaging, surgical intervention, and outcomes of these patients. The majority of patients in the study were male (29/38, with 76.3%) and the thoracic region was the most common location for the cyst (17, with 44.7%). Weakness was the primary complaint and 94.7% of patients had myelopathy. The bladder was affected in 13 patients (34.2%). Of the 38 patients, 26 (71%) had cysts in extradural locations, while the rest were intradural. In total, 45.5% of intradural cysts were located in the ventral region. Seventeen (65.4%) had dural defects along the root sleeve and 29 (76.3%) underwent complete excision. All extradural cysts underwent complete excision and repair of the dural defect. Thirty patients (78.9%) experienced improved outcomes with reduced spasticity and improved weakness. One patient developed new-onset weakness postoperatively due to epidural hematoma. The mean follow-up period was 41 months and one patient experienced a recurrence. Spinal arachnoid cyst is a rare benign spinal condition that is typically treated with surgery in symptomatic patients. Surgical intervention may involve either the excision of the cyst or marsupialization. [ABSTRACT FROM AUTHOR]

Iniencephaly is an extremely rare congenital neural tube defect (NTD) involving the occipital region with rachischisis of the cervicothoracic spine and fixed retroflexion deformity of the head. It affects an estimated 0.1–10 out of 10,000 pregnancies and carries a dismal prognosis. Most affected children are either stillborn or perish within a few hours of delivery. Pathological and postmortem studies of iniencephaly significantly outnumber the limited amount of literature available on patients surviving with this disorder. To date, surgical repair has been attempted in only 3 of the 8 patients with iniencephaly who have survived long-term. Thus, a huge knowledge gap remains regarding the neurosurgical nuances and postsurgical outcomes in iniencephaly. A 4-year-old girl presented with soft, fluctuant swelling in the suboccipital region and was subsequently diagnosed with iniencephaly. She underwent a successful surgical repair of the encephalocele with dural plication. No recurrence of swelling or new neurologic deficits were noted at a 1-year follow-up. Iniencephaly is a complex NTD associated with high perinatal mortality that requires a vigilant antenatal diagnosis. Surgical repair may be attempted in the lucky few survivors after a thorough evaluation of the anomaly. [ABSTRACT FROM AUTHOR]

Abstract: Current cancer therapeutics are identified based on initial tumor regression screens that mostly kill differentiated tumor cells, sparing the rare cancer stem cells (CSCs). Being rare and difficult to characterize, it remains a challenge to identify compounds active against them. Side population (SP) cells identified in multiple cancer cell line panels expressing mitochondrial Cytochrome C-EGFP were evaluated for identifying possible drug candidates utilizing high-throughput imaging. We identified heat shock protein 90 inhibitors as potential agents to sensitize SP cells to anticancer drugs. Hsp90 inhibitors induced down regulation of Akt leading to proteasomal degradation of survivin and consequent mitochondrial apoptosis. A successful screening platform for identifying compounds targeting drug resistant side population cells was developed. [Copyright &y& Elsevier]

The mechanisms that regulate hematopoietic stem cell (HSC) dormancy and self-renewal are well established and are largely dependent on signals emanating from the HSC niche. Recently, we found that prostate cancer (PCa) cells target the HSC niche in mouse bone marrow (BM) during metastasis. Little is known, however, as to how the HSC nichemay regulate dormancy in cancer cells. In this study,we investigated the effects of TANK binding kinase 1 (TBK1) on PCa dormancy in the BM niche. We found that binding with niche osteoblasts induces the expression of TBK1 in PCa cells PC3 and C4-2B. Interestingly, TBK1 interacts with mammalian target of rapamycin (mTOR) and inhibits its function. Rapamycin, an mTOR inhibitor, induces cell cycle arrest of PCa cells and enhances chemotherapeutic resistance of PCa cells. As a result, the knockdown of TBK1 decreases PCa stem-like cells and drug resistance in vitro and in vivo. Taken together, these results strongly indicate that TBK1 plays an important role in the dormancy and drug resistance of PCa. [ABSTRACT FROM AUTHOR]

Bone is the preferred metastasis site of advanced prostate cancer (PCa). Using an in vivo murine model of human PCa cell metastasis to bone, we noted that the majority of animals that develop skeletal metastasis have either spinal lesions or lesions in the bones of the hindlimb. Much less frequently, lesions develop in the bones of the forelimb. We therefore speculated whether the environment of the forelimb bones is not permissive for the growth of PCa. Consequently, data on tumor prevalence were normalized to account for the number of PCa cells arriving after intravascular injection, marrow cellularity, and number of hematopoietic stem cell niches. None of these factors were able to account for the observed differences in tumor prevalence. An analysis of differential gene and protein levels identified that growth arrest specific-6 (GAS6) levels were significantly greater in the forelimb versus hindlimb bone marrow. When murine RM1 cells were implanted into subcutaneous spaces in immune competent animals, tumor growth in the GAS6-/- animals was greater than in GAS6+/+ wild-type animals. In an osseous environment, the human PC3 cell line grew significantly better in vertebral body transplants (vossicles) derived from GAS6-/- animals than in vossicles derived from GAS6+/+ animals. Together, these data suggest that the differences in tumor prevalence after intravascular inoculation are a useful model to study the molecular basis of tumor dormancy. Importantly, these data suggest that therapeutic manipulation of GAS6 levels may prove useful as a therapy for metastatic disease. [ABSTRACT FROM AUTHOR]

Abstract: Tumors often acquire drug resistance due to functional loss of pro apoptotic gene Bax, a critical and essential component of cell death rendering them insensitive to most anti-tumor agents. Compounds that can induce Bax independent apoptotic cell death are expected to overcome such drug resistance. We have employed a live cell based screening platform to identify potential compounds that can induce programmed cell death in Bax deficiency. Release of cytochrome C from mitochondria into the cytosol is a decisive initial event required for the caspase dependent cell death. We have engineered both wild type and Bax knock out colon cancer cells stably expressing cytochrome C with EGFP fusion protein to identify compounds that can trigger cytochrome C release in both cells with equal efficiency. In the fluorescent translocation assay, most of the drugs tested failed to induce cytochrome C release in Bax deficient cells validating the sensitivity of the assay. This study identified five lead compounds such as thapsigargin, tunicamycine, MG132, kaempferol and camptothecin that could induce cytochrome C release in both wild type and Bax deficient cells with equal potency. All the positive hits induced ER stress signaling as evidenced by up-regulation of Grp78. Studies with a Bak deficient cells indicate that Bak deficiency confers protection to cells from ER stress through autophagy. Further studies revealed that ER stress inducing agents are capable of triggering classical mitochondrial apoptotic cell death through the conformational activation of Bak, substantiating the potential of this pathway in designing drugs against Bax deficiency mediated drug resistance. [Copyright &y& Elsevier]