Neurobrucellosis presenting as an infected cerebellopontine cistern epidermoid cyst.

Neurobrucellosis is a rare complication of brucella infection which presents as meningitis, meningoencephalitis, subdural empyema, brain abscess, myelitis, and radiculo- neuritis. We report the first case of neurobrucellosis presenting as an infected cerebellopontine cistern epidermoid cyst in a young immunocompetent male who presented with fever and acute raised intracranial pressure. MRI brain showed an extra-axial mass in the right cerebellopontine angle cistern with peripheral rim enhancement and diffusion restriction. Emergency surgery unveiled a well-encapsulated lesion containing thick pus and keratinous material, confirming an infected epidermoid cyst. Intriguingly, the culture revealed Brucella infection, but the source of the infection remained unclear.

Mapping the Landscape of Electronic Health Records and Health Information Exchange Through Bibliometric Analysis and Visualization.

The adoption of Electronic Health Records (EHRs) and the establishment of Health Information Exchange (HIE) systems have significantly transformed healthcare delivery and management. This study presents a comprehensive bibliometric analysis and visualization of the landscape surrounding EHRs and HIE to provide insights into the current state and emerging trends in this field. Leveraging advanced bibliometric methodologies, including co-citation analysis, keyword co-occurrence analysis, and network visualization techniques, we systematically map the scholarly literature spanning several decades. Our analysis reveals key thematic clusters, influential publications, prolific authors, and collaborative networks within the domain of EHRs and HIE. Furthermore, we identify significant research gaps and areas for future exploration, including interoperability challenges, privacy concerns, and the integration of emerging technologies such as artificial intelligence and blockchain. The findings of this study offer valuable insights for researchers, policymakers, and healthcare practitioners seeking to navigate and contribute to the ongoing evolution of EHRs and HIE systems, ultimately enhancing the quality, efficiency, and accessibility of healthcare services.

En bloc resection followed by gluteal advancement flap for sacral Ewing's sarcoma: A novel technique.

Ewing's sarcoma is a rare and highly aggressive bone tumor primarily affecting children and adolescents. It commonly presents in the pelvic and axial skeleton, with sacral involvement posing unique challenges due to its intricate anatomical location. This report details the case of an 18-year-old male with sacral Ewing's sarcoma, emphasizing the diagnostic, surgical, and reconstructive aspects of management. The patient presented with lower back pain, lower limb weakness, and urinary incontinence, which prompted an extensive diagnostic evaluation. Magnetic resonance imaging and computed tomography scans revealed a large lytic mass extending from the S2 vertebra to the coccyx invading the presacral space. Biopsy confirmed the diagnosis of Ewing's sarcoma, characterized by the EWS-FLI1 type 1 translocation. A multidisciplinary team comprising neurosurgeons, colorectal surgeons, and plastic surgeons was formulated. En bloc resection of the tumor, lumbopelvic fixation, and soft-tissue reconstruction using bilateral gluteus maximus advancement flaps were successfully performed. The procedure aimed to address both the oncological and functional aspects of the patient's condition. Chemotherapy and radiotherapy were administered as adjuvant therapies. At 2-year follow-up, the patient was ambulating independently with no residual tumor on imaging. This case highlights the complex nature of sacral Ewing's sarcoma and underscores the importance of a multidisciplinary approach. The described surgical technique, including the innovative use of gluteus maximus advancement flaps for soft-tissue reconstruction, contributes to reducing wound complications and promoting successful patient outcomes. The presented approach serves as a valuable addition to the armamentarium of treatment options for this challenging malignancy.

Recurrent post-operative extradural and subdural collections due to intracranial hypotension following a lumbar subarachnoid drain.

Intracranial hypotension (IH) represents a syndrome secondary to low cerebrospinal fluid pressure. This case of IH following a lumbar drain inserted before the excision of a left intraconal lesion, leading to recurrent post-operative unilateral subdural and extradural collections, was treated successfully with the evacuation of the collection and simultaneous epidural blood patch (EBP) injection. Our report provides an important perspective on the management of IH with recurrent intracranial collections and reiterates that IH should be considered when dealing with recurrent unilateral intracranial collections in the post-operative period. Evacuation with a simultaneous EBP is an effective strategy for managing IH.

Hypofractionated stereotactic radiotherapy in Spetzler Martin grades 4 and 5 arteriovenous malformations in the pediatric population: Is it a viable alternative?

OBJECTIVE: To analyze the outcomes of hypofractionated stereotactic radiotherapy (HFSRT) for Spetzler Martin grades 4 and 5 arteriovenous malformations (AVMs) in a pediatric population. METHODS: Fourteen patients with Spetzler Martin (SM) grades IV and V large AVMs who underwent HFSRT between January 2013 and July 2019 were retrospectively reviewed. All patients received HFSRT at a dose of 30-36 Gy in 5 to 6 fractions. They were followed up annually with clinical and imaging assessments to evaluate obliteration rates. RESULTS: The median age at presentation was 15 years (range 8-21 years). Ten (71%) were SM grade 4 AVMs and the rest were SM grade 5 AVMs. The majority presented with headache (8 [57%]), and 3 (21%) presented with bleeding. The median nidus volume was 39.4 cc (IQR, 31.4-52.4). Two (14%) patients had infratentorial AVMs. All of them had deep venous drainage. The median clinical follow-up duration was 75 months (range 31-107 months). There was complete obliteration of the nidus in 3 (21%) patients with a median time to obliteration of 39 months. HFSRT resulted in a reduction of the AVM volume to 12 cc or less in nearly 70% of patients. None of the patients experienced re-bleeding. 79% reported an improvement in their symptoms. CONCLUSION: HFSRT is a highly effective treatment for high-grade AVMs in children, which can result in either complete elimination or significant reduction of the nidus volume or make it suitable for additional treatment, such as single-session stereotactic radiosurgery (SRS).

Spinal Arachnoid Cyst Analysis of Surgical Experience in a Single Tertiary Care Centre and Review of Literature.

OBJECTIVE: To study patients with spinal arachnoid cysts, who underwent cyst excision with dural defect repair or marsupialization, and their outcomes. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Challenges of anaesthetising a child with Bow Hunter's syndrome and dilated cardiomyopathy for occipitocervical fusion.

Paediatric Bow Hunter's syndrome (BHS), or rotational vertebral artery syndrome, is a rare cause of posterior circulation insufficiency in children. It results from mechanical obstruction of the vertebral artery by the transverse process of cervical vertebrae resulting in vertebrobasilar insufficiency during the neck rotation to the sides. Paediatric dilated cardiomyopathy (DCM) is a rare myocardial disease that presents with ventricular dilatation and cardiac dysfunction. This case report describes the successful anaesthetic management of an boy with BHS due to atlantoaxial dislocation and DCM. The child was anaesthetised by keeping the following anaesthetic goals in mind such as maintenance of the heart rate, rhythm, preload, afterload and contractility close to the baseline for both DCM and BHS. Haemodynamic management with optimal fluids, inotrope and a vasopressor and titrating its volume and doses using multimodal haemodynamic monitoring while keeping both cardio and neuroprotective strategies, and the multimodal analgesia techniques helped the child for faster recovery.

"Undercutting of the corresponding rib": a novel technique of increasing the length of donor in intercostal to musculocutaneous nerve transfer in brachial plexus injury.

Intercostal nerves (ICN) are often utilized as donors for various neurotization procedures in brachial plexus injuries. ICN to musculocutaneous nerve (MCN) transfer is usually a standard in pan brachial plexus injuries, in order to restore flexion at the elbow. A tensionless co-aptation of the donor-recipient nerves often necessitates either a distal dissection of the ICNs where the number of fascicles is rather low or a proximal dissection, often at the cost of dissection of the serratus anterior digitation with a risk of later fibrosis and adhesion. We report two cases of pan brachial plexus injuries where ICN-MCN transfer was performed to restore elbow function. These patients underwent clinical and electrodiagnostic evaluation before surgery. We used the standard technique of harvesting ICNs 3-5, with our technical modification of "undercutting of rib" for increasing the donor length. The procedure was applied in two patients with pan brachial plexus injury (mean age = 23). Mean duration since the injury to surgery was ten months. Both patients underwent tensionless anastomosis with a combination of suture and fibrin glue co-aptation. While one patient had some improvement in elbow flexion, another one was under active rehabilitation protocol during follow-up. We found that undercutting of the ribs near serratus digitations can allow mobilization of the ICN from its groove, which in turn lengthens the donor nerve length without violating the serratus anterior digitations and without too anterior dissection of the nerve. It can be a viable option when a tensionless co-aptation at the axilla is otherwise not feasible intraoperatively.

Correction: Calpain and Reactive Oxygen Species Targets Bax for Mitochondrial Permeabilisation and Caspase Activation in Zerumbone Induced Apoptosis.

[This corrects the article DOI: 10.1371/journal.pone.0059350.].

Stage-specific response in early mouse embryos exposed to prednisolone in vitro.

Corticosteroids are increasingly being used during the peri-implantation period to treat women with repeated IVF failure and recurrent miscarriage. However, the direct effects of prednisolone (PRDL), one of the commonly used corticosteroids on early embryo development is not understood. To mimic the possible clinical scenario and to understand the embryonic response to direct PRDL exposure, this pilot study was conducted in a mouse model. Cleavage stage embryos exposed to 3 and 30 µM PRDL in vitro were assessed for peri-implantation developmental potential, genetic integrity, inner cell mass (ICM) proliferation and pluripotency markers in the proliferated ICM cells. Exposure to 30 µM PRDL delayed the embryonic progression beyond compaction (P < 0.05) in comparison to vehicle control and, had reduced total cell number (P < 0.001) than all other groups. In addition, 30 µM PRDL exposure resulted in poor hatching potential (P < 0.05) and increased apoptosis in blastocysts (P < 0.05) compared to 3 µM PRDL. On the other hand, completely formed ICM outgrowths were significantly higher (P < 0.05) in 3 µM PRDL compared to control. However, no significant differences were observed in the expression of pluripotency genes. In conclusion, the trend observed in embryos exposed to PRDL in vitro provides important information concerning the use of this drug when treating patients at the peri-implantation phase of IVF cycles. However, the clinical value of this observation on human embryo development needs further research.

Surgical Outcome in an Iniencephaly Survivor: Case Report and Review of the Literature.

BACKGROUND: 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. CASE DESCRIPTION: 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. CONCLUSION: 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.

White Epidermoid of the Sylvian Fissure Masquerading as a Dermoid Cyst: An Extremely Rare Occurrence.

We report the case of a 30-year-old female with a Sylvian fissure, white epidermoid which was radiologically looking like a dermoid cyst. The female presented with a headache with no neurological deficits. On radiology, the lesion was in Sylvian fissure, T1 hyperintense, T2 hypointense, and with minimal diffusion restriction medially. Hence a preoperative impression of dermoid cyst was made, a quite uncommon location. Intraoperatively, the classical pearly-white flaky appearance of epidermoid was seen which was confirmed histopathologically. White epidermoids appearing so because of high protein content are a rarity and are more likely to cause aseptic meningitis in the event of intraoperative spillage. Differentiating between a dermoid cyst and white epidermoid preoperatively and radiologically is difficult. Dermoids show diffusion restriction and are usually midline, whereas white epidermoids do not show diffusion restriction and are usually lateral. This is the first report of a white epidermoid in Sylvian fissure to the best of our knowledge.

Surgical excision of large-to-giant petroclival meningiomas focusing on the middle fossa approaches: The lessons learnt.

INTRODUCTION: Petroclival meningiomas are based on or arising from the petro-clival junction in upper two-thirds of clivus, medial to the fifth cranial nerve. This study focuses on the surgical experience in resecting large-giant tumors >3.5 in size predominantly utilizing middle fossa approaches. MATERIAL AND METHODS: 33 patients with a large or a giant petroclival meningioma (size >3.5 cm) were included. Clinical features, preoperative radiological details, operative findings, and postoperative clinical course at the follow-up visit were reviewed. Group A tumors (n = 17,51.5%) were sized 3.5cm-5cm, and Group B (n = 16,48.48%) tumors were of size >5 cm. Extent of resection was described as 'gross total' (no residual tumor), 'near total' (<10% residual tumor) and 'subtotal resection' (>10% residual tumor). Glasgow outcome scale (GOS) quantitatively scored postoperative neurological outcome (mean follow up: 35.77months; range 1-106 months). RESULTS: 25 (75.8%) patients had tumour extension into both supratentorial and infratentorial compartments. Extension into Meckel's cave (n = 25,75.8%), cavernous sinus (n = 17,48.4%], sphenoid sinus (n = 12,38.7%] and suprasellar area [12,38.7%] was often seen. In 31 (93.9%) patients, the tumor crossed the midline in the premedullary, prepontine, and interpeduncular cisterns. In 20 (60.6%) patients, the tumour extended below and posterior to the internal auditory meatus (IAM), while in 13 (39.4%) patients, the tumor was located above and anterior to the IAM. Kawase's approach was the most commonly used approach in 16 (48.48%) patients and resulted in maximum tumor resection. Other approaches included half-and-half (trans-Sylvian with subtemporal) [n = 6, 18.18%]; frontotemporal craniotomy with orbitozygomatic osteotomy [n = 1, 3%] and retromastoid suboccipital craniectomy (RMSO) [n = 7, 21.21%]. In 2 (6.06%) patients, staged anterior petrosectomy with RMSO; and, in 1, staged presigmoid with half-and-half approach was used. Gross total excision was achieved in 12 (36.36%), near-total excision in 15 (45.45%) and subtotal excision in 6 (18.18%) patients. 20 (60.6%) patients had a good functional outcome; 6 patients succumbed due to meningitis, pneumonitis, perforator injury or a large tumor recurrence. CONCLUSIONS: Half-and-half approach was used in tumors with middle and posterior cranial fossae components often extending to the suprasellar region. Kawase's anterior petrosectomy was utilized in resecting tumors with predominant posterior fossa component (along with a small middle fossa component) that was crossing the midline anterior to the brain stem, and mainly situated superomedial to the IAM. Tumors confined to the posterior fossa, that extended laterally and below the IAM were resected utilizing the RMSO approach. Occasionally, a combination of these approaches was used. Middle fossa approaches help in significantly avoiding morbidity by an early devascularisation and decompression of the tumor. In tumors lacking a plane of cleavage, a thin rim of capsule of tumor may be left to avoid brain stem signs.

Technical pearls and surgical outcome of early transitional period experience in minimally invasive lumbar discectomy: A prospective study.

BACKGROUND: There is growing indications of minimally invasive spine surgery. The inherent attitude and institutive learning curve limit transition from standard open surgery to minimally invasive surgery demanding understanding of new instruments and correlative anatomy. MATERIALS AND METHODS: In this prospective study, 80 patients operated for lumbar disc prolapse were included in the study (between January 2016 and March 2018). Fifty patients (Group A) operated by various minimally invasive spine surgery (MISS) techniques for herniated disc disease were compared with randomly selected 30 patients (Group B) operated between the same time interval by standard open approach. Surgical outcome with Oswestry Disability Index (ODI) and patient satisfaction score was calculated in pre- and postoperative periods. RESULTS: Mean preoperative ODI score in Group A was 31.52 ± 7.5 standard deviation (SD) (range: 6"46; interquartile range [IQR]: 8; median: 32.11) and postoperative ODI score was 9.20 ± 87.8 SD (range: 0"38; IQR: 11; median: 6.67). Mean preoperative ODI score in Group B was 26.47 ± 4.9 SD (range: 18"38; IQR: 4; median: 25) and postoperative ODI score was 12.27 ± 8.4 SD (range: 3"34; IQR: 12; median: 10.0). None of the patients was unsatisfied in either group. On comparing the patient satisfaction score among two groups, no significant difference (P = 0.27) was found. DISCUSSION: On comparing the change in ODI and preoperative ODI among both groups, we found a significant difference between the groups. It is worth shifting from open to MISS accepting small learning curve. The satisfaction score of MISS in early transition period is similar to open procedure. CONCLUSION: The MISS is safe and effective procedure even in transition period for the central and paracentral prolapsed lumbar intervertebral disc treatment. The results are comparable, and patient satisfaction and symptomatic relief are not compromised.

Brain-stem hemangioblastomas: The seemingly innocuous lesion in a perilous location.

INTRODUCTION: Hemangioblastomas [75% sporadic, 25% with Von Hippel Lindau (VHL) disease] are highly vascular, benign lesions. The surgical nuances, management, and complication avoidance in brain-stem hemangioblastomas (BHs) have been studied. MATERIAL AND METHODS: Over 18 years, 27(mean age: 29 years; range 15-60 years) consecutive cases of BH underwent microsurgical excision. All patients were assessed clinico-radiologically for neurological deficits and screened for VHL disease. Outcome of the patients was based on Karnofsky Performance Status scale (KPS). RESULTS: 12 out of 19 (70.4%) patients with hydrocephalus underwent a cerebrospinal fluid (CSF) diversion procedure. Lower cranial nerve palsy was present in 10 (37%) patients and motor weakness in 13 (48%). The tumours [mean size 3.34 ± 1.06 cm, range: 1.4-5.5 cm; 11 solid, rest solid-cystic; 18 (66.7%) subpial and 9 (33.33%) intramedullary] were divided into four categories based on size: A: <2 cm (n = 5,18.5%); B: 2-3 cm (n = 10,37%); C: 3-4 cm (n = 6,22.2%); D: >4 cm (n = 6,22.2%). Their location was at posterior cervicomedullary junction (n = 12); pontomedullary junction (n = 7); pons (n = 3), medulla (n = 3) and ponto-mesencephalic region (n = 2). Multiple flow voids were seen in >50% patients with tumour >2 cm. 5 patients had syringomyelia; and, 8 had diffuse cervical cord expansion. Two patients with a large vascular tumour underwent preoperative embolization. Six patients had VHL disease; one underwent bilateral adrenalectomy for refractory hypertension; and, the another, nephrectomy for renal cell carcinoma. Twenty-six patients underwent a midline suboccipital craniectomy; and, 1 with a cerebellopontine angle tumour, a retromastoid craniectomy. 15 patients underwent total excision; 10 patients, near-total (<10% remaining) excision, and 2 patients, a subtotal (>10% remaining)) excision. Three patients (2 with VHL disease) expired due to exsanguinating hemorrhage, spreading venous thrombosis and aspiration pneumonitis, respectively. At follow-up visit (median: 25 ± interquartile range 2-56months), 17 patients had improved KPS, 4 remained in same status and 3 (recently operated, on tracheostomy) had worsened KPS. CONCLUSIONS: Significant improvement is achievable in neurological status in patients following successful extirpation of a brain-stem hemangioblastoma, despite a turbulent perioperative period. Leaving tumour capsule adherent to the brain-stem often helps in preserving brain-stem function. Postoperatively, the patients should be monitored for their respiratory and lower cranial nerve status to prevent aspiration pneumonitis.

Capsuloganglionic Germinoma: A Rare Site for Uncommon Childhood Tumor.

Germ cell tumors (GCTs) are rare intracranial tumors with a strong predilection for children. Commonly, these tumors arise either in the suprasellar or the pineal region. The basal ganglia-thalamus complex represents a rare site of nonmidline intracranial GCTs. Such basal ganglionic GCTs have been reported to produce certain interesting clinico-radiological features, the knowledge of which may provide important diagnostic clues preoperatively. We present the case of a 9.5-year-old boy who presented with right hemiparesis and precocious puberty. Imaging revealed a heterogeneously enhancing mass involving the left capsuloganglionic region, sparing the thalamus. There was little perilesional edema and midline shift. Because of the deep location of the mass and a lack of mass effect, a neuronavigation-guided tumor biopsy was performed which unraveled a pure germinoma. The child was referred for adjuvant radiotherapy following an uneventful postoperative course. At the time of writing the report, the child was on radiotherapy and doing well.

Knock and Drill Technique: A Simple Tips for the Instrumentation in Complex Craniovertebral Junction Anomalies without using Fluoroscopy.

CONTEXT: Existence of complex variable bony and vertebral artery (VA) anomalies at craniovertebral junction (CVJ) in subset of complex CVJ anomalies demands individualized instrumentation policy and placing screws in each bone requires strategic preoperative planning and intraoperative skills. AIM: To evaluate the clinical accuracy of knock and drill (K and D) technique for the screw placement in complex CVJ anomalies. SETTINGS AND DESIGN: Prospective study and operative technical note. MATERIALS AND METHODS: Totally 36 consecutive patients (16 - pediatrics, 20 - adult patients) of complex CVJ: Complete/partial occipitalized C1 vertebra; at least one hypoplastic (C1/C2) articular mass, rotational component, and variations in the third part of VA were included in this study. Preoperative detail computed tomography (CT) CT CVJ with three-dimensional reconstruction was done for the assessment of CVJ anatomy and facet joint orientation. The accuracy of novel technique was assessed with postoperative CT to evaluate cortical breach in between 5th and 7th postoperative day in all the patients. All patients were underwent clinico-radiological evaluation at 6-month follow-up. RESULTS: Totally 144 screws were placed using K and D technique (pediatric group - 64 screws, adult patients - 80 screws). Total of 12 screws were placed in C1 lateral mass in both age group without any bony cortical breach and complication. Sixteen C2 pedicle screws and 12 C2 pars screw in pediatrics and 18 C2 pedicle screws in adult patients were placed without any bony breach or VA injury. Out of thirty subaxial lateral mass screws in pediatric group, the bony breach was encountered with one screw (3.3%). Total of 38 C2 pars screws was placed in adult group in which bony breach along with VA injury was encounter with 1screw (2.6%). CONCLUSION: A simple technique of K and D for placing a screw increases the accuracy and spectrum of bony purchase and has the potential to reduce the complication in patients with complex CVJ anomalies.

A high-throughput image-based screen for the identification of Bax/Bak-independent caspase activators against drug-resistant cancer cells.

Despite the use of new generation target specific drugs or combination treatments, drug-resistance caused by defective apoptosis signaling remains a major challenge in cancer treatment. A common apoptotic defect in drug-resistant tumor is the failure of cancer cells to undergo Bax/Bak-dependent mitochondrial permeabilization due to impaired signaling of Bcl-2 family proteins. Therefore, Bax and Bak-independent caspase-activating compounds appear to be effective in killing such tumor cells. An image-based cellular platform of caspase sensors in Bax and Bak deficient background allowed us to identify several potential Bax/Bak-independent caspase-activating compounds from a limited high-throughput compound screening. FRET-based caspase sensor probe targeted at the nucleus enabled accurate and automated segmentation, yielding a Z-value of 0.72. Some of the positive hits showed promising activity against drug-resistant human cancer cells expressing high levels of Bcl-2 or Bcl-xL. Using this approach, we describe thiolutin, CD437 and TPEN as the most potentially valuable drug candidates for addressing drug-resistance caused by aberrant expression of Bcl-2 family proteins in tumor cells. The screen also enables the quantification of multiparameter apoptotic events along with caspase activation in HTS manner in live mode, allowing characterization of non-classical apoptosis signaling.

TBK1 regulates prostate cancer dormancy through mTOR inhibition.

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 niche may 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.