Role of Angiogenesis and Its Biomarkers in Development of Targeted Tumor Therapies.

Angiogenesis plays a significant role in the human body, from wound healing to tumor progression. "Angiogenic switch" indicates a time-restricted event where the imbalance between pro- and antiangiogenic factors results in the transition from prevascular hyperplasia to outgrowing vascularized tumor, which eventually leads to the malignant cancer progression. In the last decade, molecular players, i.e., angiogenic biomarkers and underlying molecular pathways involved in tumorigenesis, have been intensely investigated. Disrupting the initiation and halting the progression of angiogenesis by targeting these biomarkers and molecular pathways has been considered as a potential treatment approach for tumor angiogenesis. This review discusses the currently known biomarkers and available antiangiogenic therapies in cancer, i.e., monoclonal antibodies, aptamers, small molecular inhibitors, miRNAs, siRNAs, angiostatin, endostatin, and melatonin analogues, either approved by the U.S. Food and Drug Administration or currently under clinical and preclinical investigations.

Metabolomics and EMT Markers of Breast Cancer: A Crosstalk and Future Perspective.

Cancer cells undergo transient EMT and MET phenomena or vice versa, along with the parallel interplay of various markers, often correlated as the determining factor in decoding metabolic profiling of breast cancers. Moreover, various cancer signaling pathways and metabolic changes occurring in breast cancer cells modulate the expression of such markers to varying extents. The existing research completed so far considers the expression of such markers as determinants regulating the invasiveness and survival of breast cancer cells. Therefore, this manuscript is crosstalk among the expression levels of such markers and their correlation in regulating the aggressiveness and invasiveness of breast cancer. We also attempted to cover the possible EMT-based metabolic targets to retard migration and invasion of breast cancer.

Effect of parthenolide, an NLRP3 inflammasome inhibitor, on insulin resistance in high-fat diet-obese mice.

The activation of Nod-like receptor proteins (NLRP3) containing the pyrin domain inflammasome is a hallmark of the pathogenesis of metabolic disorders. Inhibition of the NLRP3 inflammasome by phytoconstituents has been attempted as a strategy to mitigate these disorders. Therefore, the present study aimed to evaluate the efficacy of an NLRP3 inflammasome inhibitor, parthenolide (PN; 5 mg/kg i.p.) against inflammation and insulin resistance in high-fat diet (HFD) - obese mice. Treatment with PN and pioglitazone (PIO; 30 mg/kg p.o.) attenuated lipopolysaccharide (LPS; 1 ng/ml) - induced elevation of tumor necrosis factor-α and interleukin-1ß in mouse peritoneal macrophages in a dose-dependent manner. Sixty days of PN and PIO treatment marginally reduced obesity-induced insulin resistance in HFD-obese mice. PN treatment also decreased blood glucose from 14th to 60th day, supporting the hypothesis of simultaneous attenuation of inflammation and insulin resistance in obese mice. Thus, PN treatment was also evident with significant improvement in glucose tolerance and peripheral insulin resistance validated through the respective tolerance tests. Therefore, the present study suggests that PN, an NLRP3 inflammasome inhibitor, could be a possible therapeutic agent for attenuating obesity-induced insulin resistance.

Chemoprophylactic activity of nitazoxanide in experimental model of mammary gland carcinoma in rats.

The current study focuses on the evaluation of the chemoprophylactic activity of nitazoxanide against the mammary gland carcinoma in experimental rats. The experimental protocol involves total 50 female Wistar albino rats of body weight 120-150 g, which were randomly categorized into five groups; Normal control (1% w/v carboxymethyl cellulose, p.o.); Toxic control (N-methyl-N-nitrosourea, MNU, 47 mg/kg i.v.); Standard (MNU, 47 mg/kg i.v. + tamoxifen, 1 mg/kg p.o.); Treatment 1 (MNU, 47 mg/kg i.v. + NTZ low-dose, 25 mg/kg p.o.); and Treatment 2 (MNU, 47 mg/kg, i.v. + NTZ high-dose, 50 mg/kg p.o.). The mammary gland carcinoma was induced by a single tail vein intravenous injection of MNU at a 47 mg/kg dose. Seven days after MNU administration, daily dosing of nitazoxanide and tamoxifen was initiated till 110th day in respective groups. The MNU toxicity was apparent with the altered electrocardiogram and heart rate variability, increased number of alveolar bud count, differentiation score, and upregulated antioxidant parameters. Nitazoxanide treatment restored the histological architecture in rats along with the reduction of alveolar buds and downregulation of oxidative stress markers as well as inflammatory markers. Therefore, nitazoxanide can be utilized as a potential chemoprophylactic agent against mammary gland carcinoma induced by MNU.

Transfascial suture versus tack fixation of mesh in totally extraperitoneal repair of inguinal hernia: A prospective comparative study.

Purpose: Among laparoscopic surgeries in inguinal hernias, totally extraperitoneal (TEP) repair has demonstrated favourable results in reduction of post-operative pain and mean operative times with early return to physical activity. We have done a prospective comparative study on two different techniques of mesh fixation, i.e., transfascial suture and tack fixation. Materials and Methods: It was a prospective, non-randomised comparative study done on inguinal hernia patients operated by TEP repair from October 2014 to September 2016. These data were compared in two techniques of mesh fixation (tack and transfascial sutures) in terms of post-operative complications, pain scores by visual analogue scale (VAS) and cost analysis of the procedure. Results: Our study on 69 total patients (44 tack fixation and 25 suture fixation group) revealed that mean VAS scores for post-operative pain were not having any statistically significant difference in the tack group versus suture group (2.42 ± 0.24 vs. 2.2 ± 0.24) at 24 h, but VAS scores in the follow-up period at 1 week, 1 month, 3 months and 6 months were 1.14 ± 0.33 versus 0.67 ± 0.27; 0.78 ± 0.24 versus 0.07 ± 0.06; 0.42 ± 0.17 versus 0.07 ± 0.06 and 0.5 ± 0.11 versus 0.07 ± 0.06, respectively, which showed significant difference at 1 and 3 months, suggesting less pain in the suture group. No significant difference was noted in other post-operative complications. Conclusion: Transfascial suture fixation of mesh in TEP repair of inguinal hernia can be a cost-effective procedure with a comparable safety profile as compared to tack fixation.

Cannula-Assisted Port Placement during Video Endoscopic Inguinal Lymphadenectomy (VEIL)-a Novel and Safe Technique.

To present our novel technique for subsequent port placement during video endoscopic inguinal lymphadenectomy (VEIL) surgery. VEIL has provided positive results in terms of reduction of pain, early recovery, and better cosmesis. Ten patients who underwent VEIL procedure during 2012-2015 were included in this study to assess feasibility, safety, and advantages of port placement by our new technique which include placement of subsequent ports with the help cannula of the first port. The size of incision, time taken for port placement, leakage of pneumo, any complication(s), and potential learning curve or special instrument requirements were noted in these patients. Median incision size was 10 mm and 5 mm for their respective sized ports with this new technique. Pneumo leakage was not seen in any patient. Median time taken for subsequent port placement was 2 min ± 15 s. No complication was noted to patients or the operating surgeon. The technique proved to be feasible and needed no special equipment or training. We report technical feasibility, safety, and advantages of a new technique for port placement during VEIL surgery emphasising its potential to become a standard technique in the near future.

Role of angiotensin-converting enzyme as prognostic marker in thoracic trauma: A prospective observational study.

BACKGROUND: Chest injuries, accounting for 25% of all trauma-related deaths, are one of the main causes of death in young adults. Our priority is the early identification of life-threatening injuries both immediate and delayed. The role of various biomarkers, such as Clara cell protein 16, von Willebrand factor, interleukin-6, tumor necrosis factor, and angiopoietin, has been studied in trauma-related acute respiratory distress syndrome (ARDS). Serum angiotensin-converting enzyme (ACE) levels have been studied in non-trauma-related ARDS. The aim of this prospective observational study was to evaluate the role of ACE levels as a prognostic marker in thoracic trauma. METHODS: A prospective observational study was conducted to evaluate serum ACE levels in thoracic trauma patients and to explore its prognostic potential with regard to clinical outcome. A total of 48 thoracic trauma patients were included in the study. RESULTS: The mean ACE level in the study population was 66.54+-11.18. A strong positive correlation was found among serum ACE levels and Thoracic Trauma Severity Score (TTSS). CONCLUSION: Our study demonstrates that serum ACE levels are increased in thoracic trauma patients with higher levels, indicating the severe nature of trauma in concordance with increased TTSS scores.

Respiratory functional outcomes improvement with intervention in chronic empyema thoracis: a retrospective analysis.

INTRODUCTION: Chronic pleural empyema is usually a consequence of in adequate treatment of acute pleural empyema. The incidence of tubercular and post-intervention empyema has increased in underdeveloped or developing countries adding to economic burden on the society. We have performed a retrospective analysis on role of intervention in chronic empyema to improve respiratory functional outcomes. METHODS: We retrospectively reviewed data of 115 patients of chronic tubercular and parapneumonic empyema thoracis to evaluate change in functional outcome parameters based on their treatment modalities during follow-up in department of surgery, King George's Medical University, Lucknow, India. Accordingly, four groups were made-group 1 (tube thoracostomy), group 2 (decortication by video-assisted thoracoscopic surgery (VATS)), group 3 (decortication by open thoracotomy), and group 4 (window thoracostomy followed by thoracomyoplasty). RESULTS: Significant improvement was noted in forced expiratory volume in one second (FEV1)% and forced vital capacity (FVC)% in all groups. In spirometry, percent change in mean FEV1 from pre-intervention to post-intervention was increase of 55.4%, 38.3%, 47.2, and 59.21% in group 1, group 2, group 3, and group 4 respectively, and percent change in mean FVC from pre-intervention to post-intervention was increase of 53.30%, 38.11%, 51.23, and 54.21% in group 1, group 2, group 3, and group 4 respectively. CONCLUSION: Our study showed that a significant increase was observed in FVC and FEV1 from pre to post among all the groups. Comparable improvement of functional outcomes with non-operative intervention in properly selected patients can be achieved.

Sudden-Onset Bilateral Blindness in a Young Girl Receiving Parenteral Nutrition: Case Report and Review of Literature.

BACKGROUND: Parenteral nutrition (PN) via a central venous catheter is routinely used for surgical patients without a functioning gastrointestinal tract. Complications of PN can be metabolic and thrombotic. Blindness is a rare and unexpected complication. CASE: A young female patient with postcorrosive pyloric stenosis was started on PN through an indwelling central venous catheter. On the sixth day of PN, the patient reported sudden painless bilateral complete loss of vision. Examination revealed bilateral normal-sized pupils with normal pupillary reaction. There was complete bilateral absence of visual acuity with no perception of light. Fundus examination was normal. Magnetic resonance imaging revealed an acute infarct in the left occipital lobe, left corpus callosum, and posteromedial aspect of the left thalamus. No cardiac source of the thrombus could be identified. After supportive treatment, the vision started improving after 3 days; recovery was 95% after 10 days. A feeding jejunostomy was performed urgently under local anesthesia, and 1 month of enteral nutrition was administered. One month after the event, the patient's vision returned to normal. Definitive surgery in the form of antrectomy with Billroth II reconstruction was performed 8 weeks later. CONCLUSION: Blindness secondary to central venous catheterization is very rare; possible mechanisms are venous thrombosis with paradoxical emboli, air emboli, or accidental arterial puncture. Clinicians must exercise caution while using PN. A high index of suspicion is required to diagnose and treat unexpected complications.

Multiple impacted urethral metallic needles and screws (foreign bodies) associated with polyembolokoilamania.

This study aims to present the challenges faced in the management of multiple impacted foreign bodies, needles, and screws from the penile and bulbar urethra. A young man presented with complaint of a hard perineal swelling and passage of metallic nails per urethra. Pelvic radiograph revealed multiple foreign bodies (nails) in the penile and bulbar urethra. Successful cystoscopic removal of 11 foreign bodies comprising four large metallic screws and seven nail-like large sewing needles was done in two sessions. The most prevalent motivation for self-insertion of urethral foreign bodies is autoerotism/psychological impairment. Appropriate surgical technique guided by physical examination/ imaging with endoscopic removal is often successful, depending on the object's physical attributes and morphology while minimizing urothelial trauma and preserving voiding and erectile function. Follow-up cystourethroscopy is important for diagnosing any complications and urothelial injuries.