Therapeutic Potential of Thymoquinone in Triple-Negative Breast Cancer Prevention and Progression through the Modulation of the Tumor Microenvironment

To date, the tumor microenvironment (TME) has gained considerable attention in various areas of cancer research due to its role in driving a loss of immune surveillance and enabling rapid advanced tumor development and progression. The TME plays an integral role in driving advanced aggressive breast cancers, including triple-negative breast cancer (TNBC), a pivotal mediator for tumor cells to communicate with the surrounding cells via lymphatic and circulatory systems. Furthermore, the TME plays a significant role in all steps and stages of carcinogenesis by promoting and stimulating uncontrolled cell proliferation and protecting tumor cells from the immune system. Various cellular components of the TME work together to drive cancer processes, some of which include tumor-associated adipocytes, fibroblasts, macrophages, and neutrophils which sustain perpetual amplification and release of pro-inflammatory molecules such as cytokines. Thymoquinone (TQ), a natural chemical component from black cumin seed, is widely used traditionally and now in clinical trials for the treatment/prevention of multiple types of cancer, showing a potential to mitigate components of TME at various stages by various pathways. In this review, we focus on the role of TME in TNBC cancer progression and the effect of TQ on the TME, emphasizing their anticipated role in the prevention and treatment of TNBC. It was concluded from this review that the multiple components of the TME serve as a critical part of TNBC tumor promotion and stimulation of uncontrolled cell proliferation. Meanwhile, TQ could be a crucial compound in the prevention and progression of TNBC therapy through the modulation of the TME.     

Human Calcitonin Delivery in Rats by Iontophoresis

Abstract— In-vitro iontophoresis (0·33 mA cm⁻²) of calcitonin (50 μg mL⁻¹, pH 4) was performed with the hairless rat skin model. Direct current was as potent as pulse current (2·5 kHz on/off 1/1) iontophoresis in promoting transdermal permeation of calcitonin. Increase in duration of current application from 20 min to 1 h did not increase calcitonin flux. Results suggest that calcitonin can be blocked in the skin pores through which it travels or can accumulate in the skin and be progressively released from the depot. Invivo experiments showed that transdermal iontophoretic administration of calcitonin induced a hypocalcaemic effect in rats.     

Findings on intraprocedural non-contrast computed tomographic imaging following hepatic artery embolization are associated with development of contrast-induced nephropathy

BACKGROUNDContrast-induced nephropathy (CIN) is a reversible form of acute kidney injury that occurs within 48-72 h of exposure to intravascular contrast material. CIN is the third leading cause of hospital-acquired acute kidney injury and accounts for 12% of such cases. Risk factors for CIN development can be divided into patient- and procedure-related. The former includes pre-existing chronic renal insufficiency and diabetes mellitus. The latter includes high contrast volume and repeated exposure over 72 h. The incidence of CIN is relatively low (up to 5%) in patients with intact renal function. However, in patients with known chronic renal insufficiency, the incidence can reach up to 27%.AIMTo examine the association between renal enhancement pattern on non-contrast enhanced computed tomographic (CT) images obtained immediately following hepatic artery embolization with development of CIN.METHODSRetrospective review of all patients who underwent hepatic artery embolization between 01/2010 and 01/2011 (n = 162) was performed. Patients without intraprocedural CT imaging (n = 51), combined embolization/ablation (n = 6) and those with chronic kidney disease (n = 21) were excluded. The study group comprised of 84 patients with 106 procedures. CIN was defined as 25% increase above baseline serum creatinine or absolute increase ≥ 0.5 mg/dL within 72 h post-embolization. Post-embolization CT was reviewed for renal enhancement patterns and presence of renal artery calcifications. The association between non-contrast CT findings and CIN development was examined by Fisher’s Exact Test.RESULTSCIN occurred in 11/106 (10.3%) procedures (Group A, n = 10). The renal enhancement pattern in patients who did not experience CIN (Group B, n = 74 with 95/106 procedures) was late excretory in 93/95 (98%) and early excretory (EE) in 2/95 (2%). However, in Group A, there was a significantly higher rate of EE pattern (6/11, 55%) compared to late excretory pattern (5/11) (P < 0.001). A significantly higher percentage of patients that developed CIN had renal artery calcifications (6/11 vs 20/95, 55% vs 21%, P = 0.02).CONCLUSIONA hyperdense renal parenchyma relative to surrounding skeletal muscle (EE pattern) and presence of renal artery calcifications on immediate post-HAE non-contrast CT images in patients with low risk for CIN are independently associated with CIN development.     

Is Ustekinumab Effective in Refractory Crohn’s Disease of the Pouch and Chronic Pouchitis? A Systematic Review

Digestive Diseases and Sciences - Crohn’s disease (CD) of the pouch and chronic pouchitis represent the most common long-term complications of total proctocolectomy and ileal pouch anal...     

The efficacy of postoperative pain management with ketorolac for day case oral surgery

The efficacy of the non-steroidal anti-inflammatory analgesic, ketorolac (Toradol), was investigated in 52 day case patients undergoing removal of impacted third molar teeth under intravenous sedation and local analgesia. The study was double-blind, randomized and placebo-controlled. A single 30 mg dose of ketorolac was administered intravenously just prior to induction of sedation with midazolam. Ketorolac was well tolerated and provided good postoperative analgesia. It is suggested that ketorolac is a useful addition to the analgesic armamentarium and appropriately prescribed, provides good pain relief following day case oral surgery.     

Use of streptokinase as a recall antigen for lymphocyte proliferation testing in vitro

The use of streptokinase (SK) as a recall antigen (Ag) for stimulation of human lymphocyte proliferation in vitro was evaluated. SK is a potent stimulant, inducing a greater response than three other Ags, tetanus toxoid, Candida albicans extract, or streptolysin. The optimum stimulatory concentration is 1000 U/ml, and peak stimulation occurs between days 6 and 8. Human cord-blood lymphocytes do not respond to SK, suggesting that it is an Ag and not a mitogen. The response rate in an adult population was 82%, higher than the rate of two other Ags tested (tetanus toxoid or Candida). These findings demonstrate the ability of SK to act as a potent recall Ag for human lymphocyte proliferation in vitro.     

New onset hypertension after transplantation

It has been reported that up to 90% of organ transplant recipients have suboptimal blood pressure control. Uncontrolled hypertension is a well-known culprit of cardiovascular and overall morbidity and mortality. In addition, rigorous control of hypertension after organ transplantation is a crucial factor in prolonging graft survival. Nevertheless, hypertension after organ transplantation encompasses a broader range of causes than those identified in non-organ transplant patients. Hence, specific management awareness of those factors is mandated. An in-depth understanding of hypertension after organ transplantation remains a debatable issue that necessitates further clarification. This article provides a comprehensive review of the prevalence, risk factors, etiology, complications, prevention, and management of hypertension after organ transplantation.     

A phase III randomized clinical trial comparing laparoscopic or robotic radical hysterectomy with abdominal radical hysterectomy in patients with early stage cervical cancer

STUDY OBJECTIVE: Cervical cancer is a significant health problem in countries of the developing world. Although case series suggest advantages of total laparoscopic radical hysterectomy (TLRH) compared with total abdominal radical hysterectomy (TARH), no randomized controlled trial is currently available to establish TLRH as the new standard treatment. In this study, TLRH or total robotic radical hysterectomy (TRRH) will be performed without a vaginally assisted portion of the procedure. DESIGN: A biphasic randomized controlled trial was designed to test feasibility of recruitment and equivalence in regard to disease-free survival (Canadian Task Force classification I). SETTING: Tertiary referral hospital. PATIENTS: Patients with histologically confirmed invasive squamous cell carcinoma or adenocarcinoma of the cervix, stage IA1 (with lymphovascular space invasion), IA2, and IB1 are eligible. INTERVENTIONS: During the first phase, 100 patients will be randomized (1:1) to receive either TLRH/TRRH or TARH, with the primary end point being the rate of enrollment. During the second phase, recruitment will be extended by another 640 patients in a 1:1 TLRH/TRRH:TARH allocation, to determine equivalence with respect to disease-free survival with 80% power and alpha=0.05. MEASUREMENTS AND MAIN RESULTS: Equivalence will be assumed if the difference in disease-free survival does not exceed 7% at 4 years. Secondary outcomes include treatment-related morbidity, costs and cost effectiveness, patterns of recurrence, quality of life, pelvic floor function, feasibility of intraoperative sentinel node sampling, and overall survival. All data from this multicenter study will be entered using online electronic case report forms, allowing real-time assessment of data completeness and patient follow-up. CONCLUSION: This prospective trial aims to show the equivalence of a TLRH/TRRH versus TARH approach for patients with early stage cervical cancer following a 2-phase protocol. This trial was developed and designed with the input and approval of the members of the Gynecologic Oncology Committee from the American Association of Gynecologic Laparoscopists.     

Robotic radical parametrectomy and pelvic lymphadenectomy in patients with invasive cervical cancer

ObjectiveWe describe a series of patients diagnosed with invasive cervical cancer after undergoing simple hysterectomy who subsequently underwent robotic radical parametrectomy and bilateral pelvic lymphadenectomy. The goal of this study is to report on the safety and feasibility of robotic radical parametrectomy.MethodsA retrospective review was performed of all patients who underwent robotic radical parametrectomy and bilateral pelvic lymphadenectomy at our institution during the period December 2006 to February 2008. We analyzed our data to evaluate the safety and feasibility of performing robotic radical parametrectomy.ResultsThis analysis included 5 patients with invasive squamous cell carcinoma of the cervix. The median body mass index was 23.8 kg/m² (range, 17.7 to 26.5). The median operative time was 365 min (range, 331 to 430). The median estimated blood loss was 100 mL (range, 50 to 175). There were no conversions to laparotomy. There was 1 intraoperative complication—cystotomy. No patient required blood transfusion. The median length of hospital stay was 1 day (range, 1 to 2). One patient experienced two postoperative complications, a vesicovaginal fistula and a lymphocyst. No patient had residual tumor in the parametrectomy specimen, and no patient underwent adjuvant therapy. The median number of pelvic lymph nodes removed was 14 (range, 6 to 16). The median follow-up for all patients was 7.5 months (range, 1.3 to 13.8). There were no recurrences.ConclusionRobotic radical parametrectomy and bilateral pelvic lymphadenectomy is feasible and safe and can be performed with an acceptable complication rate.