Citalopram, an antipsychotic agent, induces G1/G0 phase cell cycle arrest and promotes apoptosis in human laryngeal carcinoma HEP-2 cells.

Human laryngeal squamous carcinoma (LSCC) is a common malignant tumor in the head and neck. Despite the recently developed therapies for the treatment of LSCC, patients' overall survival rate still did not enhance remarkably; this highlights the need to formulate alternative strategies to develop novel treatments. The antitumor effects of antidepressant drugs such as citalopram have been reported on several cancer cells; however, they have yet to be investigated against LSCC. The current study was directed to explore the possible antitumor effects of citalopram on human laryngeal carcinoma cell lines (HEP-2). HEP-2 cells were cultured and treated with different doses of citalopram (50-400 µM) for 24, 48, and 72 h. The effects of citalopram on the viability of cancer cells were determined by the MTT assay. In addition, apoptosis and cell cycle analysis were performed by flow cytometry. Moreover, evaluation of the expression of proapoptotic and apoptotic proteins, such as cytochrome c, cleaved caspases 3 and 9, Bcl-2, and BAX, was performed by western blotting analysis. Our results revealed that citalopram significantly suppressed the proliferation of HEP-2 cells through the upregulation of p21 expression, resulting in the subsequent arrest of the cell cycle at the G0/G1 phase. Furthermore, citalopram treatment-induced HEP-2 cell apoptosis; this was indicated by the significant increase of cytochrome c, cleaved caspases 3 and 9, and BAX protein expression. On the contrary, Bcl-2 protein expression was significantly downregulated following treatment with citalopram. The ultrastructure studies were in accordance with the protein expression findings and showed clear signs of apoptosis with ring chromatin condensation upon treatment with citalopram. These findings suggest that citalopram's anti-tumor activities on HEP-2 cells entailed stimulation of the intrinsic apoptotic pathway, which was mediated via Bcl-2 suppression.

Niosomes loading N-acetyl-L-cysteine for cancer treatment in vivo study.

Scientists are seeking to find an effective treatment for tumors that has no side effects. N-Acetyl-l-cysteine (NAC) is a thiol compound extracted from garlic. Current study explores the potential of NAC-loaded niosomes (NAC-NIO) for tumor treatment in mice. NAC-loaded niosomes' efficiency, morphology, UV absorption, size distribution, zeta potential, release, and FTIR analysis were evaluated. For vivo study, 25 male BALB/c mice were divided to five groups: gp1 negative control (receive saline), gp2 positive control (tumor group), gp3 treated with NAC, gp4 treated with NAC-NIO at the same time of tumor injection, and gp5 treated with NAC-NIO after tumor growth (day 14). The impact of NAC-NIO on the tumor treatment was evaluated by measuring tumor size progress, comet assay, oxidative stress parameters (GSH, nitric oxide, MDA), western blot analysis, and histopathological investigation of tissues. NAC-NIO showed 72 ± 3% encapsulation efficiency and zeta potential - 5.95 mV with spherical shape. It was found that oral administration of NAC-NIO in a dose of 50 mg/kg provided significant protection against tumor cells. Our formulation decreases DNA injury significantly (P < 0.05). It was noticed that NAC-NIO can increase oxidative stress levels in tumor tissue. On the other hand, the caspase 3 and caspase 9 gene expression were upregulated significantly (P < 0.001) in mice administrated NAC-NIO compared with all other groups. Histological studies confirmed the protective effect of NAC-NIO against tumor especially for treatment during tumor growth protocol. The results suggested that oral delivery of NAC-NIO formulation improved antioxidant effect.

Dandy-Walker syndrome associated with a giant occipital meningocele: A case report and a literature review.

Background: Dandy-Walker malformation or syndrome is the most common posterior fossa malformation. It is commonly associated with other congenital anomalies such as cardiac defects; however, association with a giant occipital meningocele is extremely rare, as only around 34 cases have been described. Case description: We report a case of a 2-month-old female infant who presented with a midline, gigantic mass in the back of the head. It was first discovered on a prenatal ultrasound. The mass measured about 15 × 5 cm, extending to the midback, not changing in size with crying, not attached to the back, and with a positive transillumination test. The diagnosis was confirmed after doing a brain computed tomography, which revealed hypoplasia of the vermis with an enlarged posterior fossa as well as cystic dilation of both ventricles with herniation through a bone defect. Conclusion: Our case highlights a rare association between giant occipital meningocele and Dandy-Walker syndrome that is rarely discussed or reported in the medical literature. By reporting this extremely rare case of Dandy-Walker syndrome associated with a giant occipital meningocele, we hope to contribute to the creation of a database for future research so that a management protocol can be established for use by clinicians and neurosurgeons for better management of the condition.

The Role of ATP-Binding Cassette Subfamily A in Colorectal Cancer Progression and Resistance.

Colorectal cancer (CRC) is one of the most common malignancies worldwide; it is the fourth leading cause of cancer-related deaths. CRC arises due to mutations that can affect oncogenes, tumour suppressor genes and DNA repair genes. The lack of novel diagnostic and therapeutic targets and the development of chemoresistance are some of the major issues when dealing with CRC. The overexpression of ATP-binding cassette (ABC) transporters is considered one facilitating mechanism for chemoresistance. Furthermore, ABC transporters have additional roles in cancer development beyond multidrug resistance. In CRC, lipid dysregulation has a key role in tumour development and progression, as cancer cells rely on lipids for energy and rapid cell proliferation. ABC subfamily A (ABCA) contains the largest members of ABC proteins, mainly known for their role in lipid transport, mostly membrane lipids such as cholesterol and phospholipids. Although the exact mechanism of action of these members is not confirmed, their expression is usually correlated with tumour progression and therapy resistance, probably due to their role in lipid homeostasis. CRC shows alteration in the expression of ABCA transporters, which is usually linked to poor prognosis and overall survival. Therefore, as lipid transporters, their role in CRC is investigated, and their diagnostic and prognostic potential is evaluated. This minireview presents evidence from various studies suggesting that ABCA transporters might have an active role in CRC and can be utilized as potential diagnostic and therapeutic targets.

Vitamin D Exerts Significant Antitumor Effects by Suppressing Vasculogenic Mimicry in Breast Cancer Cells.

Background: Numerous clinical and experimental observations have alluded to the substantial anti-neoplastic role of vitamin D in breast cancer (BC), primarily by inducing apoptosis and affecting metastasis. Tumor progression and resistance to chemotherapy have been linked to vasculogenic mimicry (VM), which represents the endothelial-independent formation of microvascular channels by cancer cells. However, the effect of vitamin D on VM formation in BC has not been thoroughly investigated. This study examined the impact of 1α,25-dihydroxyvitamin D3 (calcitriol), the active form of vitamin D, on the expression of major factors involved in BC migration, invasion, and VM formation. Experimental Methods: Publicly available transcriptomic datasets were used to profile the expression status of the key VM markers in vitamin D-treated BC cells. The in silico data were validated by examining the expression and activity of the key factors that are involved in tumor progression and MV formation in hormone-positive MCF-7 and aggressive triple-negative MDA-MB-231 BC cells after treatment with calcitriol. Results and Discussions: The bioinformatics analysis showed that tumor VM formation-enriched pathways were differentially downregulated in vitamin D-treated cells when compared with control counterparts. Treatment of BC cells with calcitriol resulted in increased expression of tissue inhibitors of metalloproteinases (TIMPs 1 and 2) and decreased content and gelatinolytic activity of matrix metalloproteinases (MMPs 2 and 9). Furthermore, calcitriol treatment reduced the expression of several pro-MV formation regulators including vascular endothelial growth factor (VEGF), tumor growth factor (TGF-ß1), and amphiregulin. Eventually, this process resulted in a profound reduction in cell migration and invasion following the treatment of BC cells with calcitriol when compared to the controls. Finally, the formation of VM was diminished in the aggressive triple-negative MDA-MB-231 cancer cell line after calcitriol treatment. Conclusion: Our findings demonstrate that vitamin D mediates its antitumor effects in BC cells by inhibiting and curtailing their potential for VM formation.

Radio-carpal wrist MR arthrography: comparison of ultrasound with fluoroscopy and palpation-guided injections.

OBJECTIVE: To compare ultrasound- (US), fluoroscopy- (FL), and palpation-guided contrast injection techniques used for dorsal radio-carpal wrist MRA. MATERIALS AND METHODS: Patients with chronic wrist pain were randomized as to which injection technique they underwent into three groups of 50 participants. Dorsal radio-carpal contrast injection was performed under US, FL guidance (one radiologist for each), or palpation guidance by an orthopedic surgeon. The three techniques were compared by procedure time, success rate, number of attempts needed, frequency and grade of extravasation, joint distension, and MRA image quality. Additionally, any change from baseline wrist pain was recorded using the visual analog scale (VAS) at five time points (immediately, 8 h, 24 h, 48 h, and 1 week) after injection. RESULTS: One hundred and fifty patients (83 males and 67 females; mean age 29 ± 6.5 years) were included. Success rates for US- and FL-guided injections were 100%, while palpation-guided approach was significantly less successful (72%) (P = 0.02) with significantly more frequent extravasation (56%)(P < 0.001). US guidance was the least time-consuming (6.5 ± 1.6 min) compared to FL guidance (12.5 ± 1.9 min) and palpation guidance (8 ± 1.2 min) (all P < 0.001). The mean number of joint puncture attempts was significantly lower with imaging-guided techniques (1.1 ± 0.24 and 1.2 ± 0.4 for US and FL, P = 0.23) compared to palpation-guided one (1.6 ± 0.8) (P = 0.007). The largest increases in baseline-pain were 8-h post-injection, and US guidance was the least painful at all-time points (all P < 0.05). Joint distension and image quality were significantly better with imaging-guided techniques (P < 0.001 and P = 0.003). CONCLUSIONS: US-guided radio-carpal injection is a less time-consuming, more tolerable, and successful radiation-free method when compared to FL guidance. Palpation-guided injections require multiple attempts to enter the joint with high failure rates and frequent extravasation.

Vitamin D-Mediated Anti-cancer Activity Involves Iron Homeostatic Balance Disruption and Oxidative Stress Induction in Breast Cancer.

Background: Vitamin D deficiency associates with high risk of breast cancer (BRCA) and increased cellular iron. Vitamin D exerts some of its anti-cancer effects by regulating the expression of key iron regulatory genes (IRGs). The association between vitamin D and cellular iron content in BRCA remains ambiguous. Herein, we addressed whether vitamin D signaling exerts a role in cellular iron homeostasis thereby affecting survival of breast cancer cells. Methods: Expression profile of IRGs in vitamin D-treated breast cancer cells was analyzed using publicly available transcriptomic datasets. After treatment of BRCA cell lines MCF-7 and MDA-MB-231 with the active form of vitamin D, labile iron content, IRGs protein levels, oxidative stress, and cell survival were evaluated. Results: Bioinformatics analysis revealed several IRGs as well as cellular stress relates genes were differentially expressed in BRCA cells. Vitamin D treatment resulted in cellular iron depletion and differentially affected the expression of key IRGs protein levels. Vitamin D treatment exerted oxidative stress induction and alteration in the cellular redox balance by increasing the synthesis of key stress-related markers. Collectively, these effects resulted in a significant decrease in BRCA cell survival. Conclusion: These findings suggest that vitamin D disrupts cellular iron homeostasis leading to oxidative stress induction and cell death.

Histone Modification in NSCLC: Molecular Mechanisms and Therapeutic Targets.

Lung cancer is the leading cause of cancer mortality in both genders, with non-small cell lung cancer (NSCLC) accounting for about 85% of all lung cancers. At the time of diagnosis, the tumour is usually locally advanced or metastatic, shaping a poor disease outcome. NSCLC includes adenocarcinoma, squamous cell carcinoma, and large cell lung carcinoma. Searching for novel therapeutic targets is mandated due to the modest effect of platinum-based therapy as well as the targeted therapies developed in the last decade. The latter is mainly due to the lack of mutation detection in around half of all NSCLC cases. New therapeutic modalities are also required to enhance the effect of immunotherapy in NSCLC. Identifying the molecular signature of NSCLC subtypes, including genetics and epigenetic variation, is crucial for selecting the appropriate therapy or combination of therapies. Epigenetic dysregulation has a key role in the tumourigenicity, tumour heterogeneity, and tumour resistance to conventional anti-cancer therapy. Epigenomic modulation is a potential therapeutic strategy in NSCLC that was suggested a long time ago and recently starting to attract further attention. Histone acetylation and deacetylation are the most frequently studied patterns of epigenetic modification. Several histone deacetylase (HDAC) inhibitors (HDIs), such as vorinostat and panobinostat, have shown promise in preclinical and clinical investigations on NSCLC. However, further research on HDIs in NSCLC is needed to assess their anti-tumour impact. Another modification, histone methylation, is one of the most well recognized patterns of histone modification. It can either promote or inhibit transcription at different gene loci, thus playing a rather complex role in lung cancer. Some histone methylation modifiers have demonstrated altered activities, suggesting their oncogenic or tumour-suppressive roles. In this review, patterns of histone modifications in NSCLC will be discussed, focusing on the molecular mechanisms of epigenetic modifications in tumour progression and metastasis, as well as in developing drug resistance. Then, we will explore the therapeutic targets emerging from studying the NSCLC epigenome, referring to the completed and ongoing clinical trials on those medications.

Multidrug Resistance and Flaring up of Manifestation in Fistulizing Crohn's Disease after Surgery on a Perianal Lesion.

Crohn's disease is a chronic inflammatory disease of the gastrointestinal tract with relapsing and remitting episodes. Abscesses and fistulas are the most common presentations of anorectal Crohn's disease. Antibiotics and surgical incision and drainage have been successful in treating perianal disease. We present here a 48-year-old woman with known case of Crohn's disease who presented with massive swelling in the perianal region with severe throbbing pain and high-grade fever, 38.2°C; the surgeon noted a large perianal abscess near the anal verge with redness, hotness, and tenderness. One and a half months from perianal abscess surgery, culture sensitivity was done due to delayed wound healing and passage of greenish discharge, and it revealed highly resistant bacteria Proteus mirabilis, Escherichia coli, and Staphylococci. In conclusion, clinicians should be aware that abscess and fistula have a fair chance to develop in Crohn's disease patients who are using immunomodulating and immunosuppressant therapy. In abscess and fistula cases, surgery should be determined as soon as possible, and close clinical monitoring should be performed. We recommend routine screening for enteric fistula and culture sensitivity of any discharge prior to the initiation of any antibiotic. Appropriate intervention should then be undertaken.

Evaluation of Tonsillotomy Effects on Pharyngeal Volume and Compliance in Children.

Our objective was to assess whether adenotonsillotomy improved pharyngeal compliance, which is a risk factor for sleep-disordered breathing. Otherwise healthy children underwent Obstructive Sleep Apnea (OSA)-18 questionnaire and a pre- and postoperative acoustic pharyngometry in both sitting and supine positions, allowing the measurement of the volume of the palatine tonsil region and pharyngeal compliance. Thirty-five children (median age 5.3 years) were enrolled; they were reevaluated at a median of 18 days (25th-75th percentiles, 15-25) after surgery. Participants were compared according to a normal (n = 18) or an increased (n = 17) preoperative pharyngeal compliance. Surgery was associated with a significant decrease in OSA-18 and Brodsky scores, with a median increase in palatine volume of 0.13 cm3 (25th-75th percentiles, 0.00-0.73). A decrease in pharyngeal compliance was observed in children with increased preoperative compliance. The variation of palatine volume after surgery was positively related to the variation of pharyngeal compliance, suggesting that obstruction relief was associated with muscle relaxation in children with normal preoperative compliance.

IgA nephropathy: Missed diagnosis and renal transplant.

The most common form of chronic glomerulonephritis worldwide is IgA nephropathy (IgAN) where IgA immune complexes are deposited in the glomeruli. About 40%-45% of patients with IgAN present with macroscopic hematuria. Diagnosis occurs through kidney biopsy to visualize IgA deposition in the glomerular mesangial area using immunofluorescence microscopy. We presented a 21-year-old patient referred to the nephrology department for follow-up after renal transplantation. His condition started at the age of nine-year with macroscopic hematuria. At the age of 14 years, he presented with hematuria and serum creatinine of 62 umol/L and was diagnosed with acute cystitis. At the age of 18 years, the patient was admitted with generalized fatigue, muscle cramps, and gross hematuria. Kidney biopsy showed advanced glomerulosclerorosis and IgAN with mesangial hypercellularity. The patient was started on peritoneal dialysis for four months following which he underwent kidney transplant from a nonrelative living donor.

Effect of surgically-induced weight loss on inflammatory mediators and peripheral blood monocyte CD11b expression in morbid obesity.

Obesity is characterized by a state of chronic mild inflammation, with raised circulating levels of inflammatory markers. Expression and release of inflammation-related adipokines, generally, rise as adipose tissue expands. In the present study we evaluated the level of serum mediators concerned in inflammation and monocyte activation (TNF-alpha, hs-CRP, MCP-1) together with percentage of CD11-b expression on monocytes in a group of morbidly obese individuals (n = 20) before and (3-6 months) after restrictive surgery, and in 15 healthy normal weight individuals. Serum MCP-1, TNF-alpha and hs-CRP were assayed by enzymatic immunoassay, while the percentage of CD11b expression on monocytes was assayed by flow cytometry. The total lipid profile and random blood glucose levels were also assessed. Morbidly obese individuals ( before surgical weight loss) had significantly increased levels of MCP-1, TNF-alpha, hs-CRP, CD11b expression on monocytes as compared to controls (P < 0.01). Levels of MCP-1, TNF-alpha, hs-CRP were significantly decreased 3 to 6 months after restrictive surgery than before the operation (P < 0.01). hs-CRP, MCP-1 and TNF-alpha were positively correlated versus each other. TNF-alpha and hs-CRP also showed positive correlation with the body mass index. Our data suggested that the studied serum and monocyte parameters may link obesity with systemic inflammation and metabolic disorders. The interactions of MCP-1, CD11b and other inflammatory parameters might provide the basis for development of new therapies for this syndrome.