Radiation-induced effects and the immune system in cancer

Chemotherapy and radiation therapy (RT) are standard therapeutic modalities for patients with cancers, and could induce various tumor cell death modalities, releasing tumor-derived antigens as well as danger signals that could either be captured for triggering anti-tumor immune response. Historic studies examining tissue and cellular responses to RT have predominantly focused on damage caused to proliferating malignant cells leading to their death. However, there is increasing evidence that RT also leads to significant alterations in the tumor microenvironment, particularly with respect to effects on immune cells and infiltrating tumors. This review will focus on immunologic consequences of RT and discuss the therapeutic reprogramming of immune responses in tumors and how it regulates efficacy and durability to RT

Adaptogens Stimulate Neuropeptide Y and Hsp72 Expression and Release in Neuroglia Cells

The beneficial stress–protective effect of adaptogens is related to the regulation of homeostasis via mechanisms of action associated with the hypothalamic–pituitary–adrenal axis and the regulation of key mediators of the stress response, such as molecular chaperones, stress-activated c-Jun N-terminal protein kinase, forkhead box O transcription factor, cortisol, and nitric oxide (NO). However, it still remains unclear what the primary upstream targets are in response to stimulation by adaptogens. The present study addresses this gap in our knowledge and suggests that an important target for adaptogen mediated stress–protective effector functions is the stress hormone neuropeptide Y (NPY). We demonstrated that ADAPT-232, a fixed combination of adaptogens Eleutherococcus senticosus root extract, Schisandra chinensis berry extract, Rhodiola rosea root extract SHR-5, and its active constituent salidroside, stimulated the expression of NPY and 72 kDa heat shock protein (Hsp72) in isolated human neuroglia cells. The central role of NPY was validated in experiments in which pre-treatment of human neuroglia cells with NPY-siRNA and HSF1-siRNA resulted in the significant suppression of ADAPT-232-induced NPY and Hsp72 release. Taken together our studies suggest that the stimulation and release of the stress hormones, NPY and Hsp72, into systemic circulation is an innate defense response against mild stressors (ADAPT-232), which increase tolerance and adaptation to stress

Combined Hyperthermia and Radiotherapy for the Treatment of Cancer

Radiotherapy is used to treat approximately 50% of all cancer patients, with varying success. Radiation therapy has become an integral part of modern treatment strategies for many types of cancer in recent decades, but is associated with a risk of long-term adverse effects. Of these side effects, cardiac complications are particularly relevant since they not only adversely affect quality of life but can also be potentially life-threatening. The dose of ionizing radiation that can be given to the tumor is determined by the sensitivity of the surrounding normal tissues. Strategies to improve radiotherapy therefore aim to increase the effect on the tumor or to decrease the effects on normal tissues, which must be achieved without sensitizing the normal tissues in the first approach and without protecting the tumor in the second approach. Hyperthermia is a potent sensitizer of cell killing by ionizing radiation (IR), which can be attributed to the fact that heat is a pleiotropic damaging agent, affecting multiple cell components to varying degrees by altering protein structures, thus influencing the DNA damage response. Hyperthermia induces heat shock protein 70 (Hsp70; HSPA1A) synthesis and enhances telomerase activity. HSPA1A expression is associated with radioresistance. Inactivation of HSPA1A and telomerase increases residual DNA DSBs post IR exposure, which correlates with increased cell killing, supporting the role of HSPA1A and telomerase in IR-induced DNA damage repair. Thus, hyperthermia influences several molecular parameters involved in sensitizing tumor cells to radiation and can enhance the potential of targeted radiotherapy. Therapy-inducible vectors are useful for conditional expression of therapeutic genes in gene therapy, which is based on the control of gene expression by conventional treatment modalities. The understanding of the molecular response of cells and tissues to ionizing radiation has lead to a new appreciation of the exploitable genetic alterations in tumors and the development of treatments combining pharmacological interventions with ionizing radiation that more specifically target either tumor or normal tissue, leading to improvements in efficacy

Cleidocranial dysplasia: Radiological mimic of pyknodysostosis – A case report

Cleidocranial dysplasia (CCD) is a rare autosomal dominant skeletal disorder with predominant membranous bone involvement. It may also occur as a sporadic mutation. The diagnosis of this condition is based on the clinical, radiological and genetic findings. It is characterised by hypoplasia or aplasia of the lateral thirds of the clavicles; craniofacial and dental anomalies; and hypoplastic iliac bones. Pyknodysostosis is a close radiological mimic of this entity. Definite diagnosis is based on the genetic analysis. A 36-year-old short-statured female was referred for computed tomography of the paranasal regions for complaints of a deviated nasal septum and midline depression in her forehead. Skeletal screening demonstrated an open metopic suture, wormian bones, maxillary hypoplasia, maldentition and aplastic lateral thirds of both clavicles. In this article, we report a case of CCD, discuss various overlapping features between CCD and pyknodysostosis and attempt to differentiate them radiologically

C-Lobe of Lactoferrin: The Whole Story of the Half-Molecule

Lactoferrin is an iron-binding diferric glycoprotein present in most of the exocrine secretions. The major role of lactoferrin, which is found abundantly in colostrum, is antimicrobial action for the defense of mammary gland and the neonates. Lactoferrin consists of two equal halves, designated as N-lobe and C-lobe, each of which contains one iron-binding site. While the N-lobe of lactoferrin has been extensively studied and is known for its enhanced antimicrobial effect, the C-lobe of lactoferrin mediates various therapeutic functions which are still being discovered. The potential of the C-lobe in the treatment of gastropathy, diabetes, and corneal wounds and injuries has been indicated. This review provides the details of the proteolytic preparation of C-lobe, and interspecies comparisons of its sequence and structure, as well as the scope of its therapeutic applications

Successful Early Non-Operative Management of Congenital Knee Dislocation: Demonstration via a Case Report

Congenital knee dislocation (CKD) is a deformity in which unnatural hyperextension is possible at the knee much beyond the normal 0° full extension while the flexion is severely restricted. Incidence of this rare congenital malformation is 1/100,000 live births. We present a clinical case of unilateral CKD in a 2-week-old female child and our approach of treatment using serial casting. We have been able to demonstrate that if initiated early, within first few weeks of life, the congenital deformity of knee can be managed conservatively without any surgical intervention even in higher grades

Spontaneous rupture of extensor pollicis longus tendon: demonstration of extensor indices proprius transfer technique

СУХОЖИЛИЯ ТРАВМЫ /ХИРРАЗРЫВ СУХОЖИЛИЯ /ХИРРАЗГИБАТЕЛЬ БОЛЬШОГО ПАЛЬЦАТКАНИ ТРАНСПЛАНТАЦИЯПЕРЕСАДКА ТКАНИВОССТАНОВЛЕНИЕ ФУНКЦИЙКЛИНИЧЕСКИЕ СЛУЧАИВ настоящее время при разрыве сухожилия длинного разгибателя большого пальца кисти нет единой схемы хирургического лечения. В статье представлен результат лечения пациента со спонтанным разрывом сухожилия длинного разгибателя большого пальца кисти в IV зоне по Б. Бойчеву, с подтверждением нарушения по данным ультразвукового исследования. В оперативном лечении нами был использован метод Pulvertaft (пересадка сухожилия собственного разгибателя указательного пальца на сухожилие длинного разгибателя большого пальца кисти). Через 3 месяца после операции пациент достиг полного объема движений большим пальцем и показал полное функциональное восстановление. Ультразвуковое исследование может рассматриваться как достаточно точное и экономически выгодное диагностическое обследование при оценке случаев с подозрением на разрыв сухожилия длинного разгибателя большого пальца кисти и тендинозом. Этот случай показывает, что метод пересадки сухожилия собственного разгибателя указательного пальца на сухожилие длинного разгибателя большого пальца кисти является эффективным и надежным хирургическим пособием.Till now no single scheme of surgical treatment has gained wide acceptance in rupture of extensor pollicis longus tendon (EPL). The result of treatment of a patient with spontaneous rupture of EPL in IV zone by B. Boichev with ultrasonographic examination is presented in the paper. In surgical treatment we used Pulvertaft technique in transfer of tendon of m. extensor indicis proprius (EIP) to EPL. After 3 months of surgery the patient showed a full range of motions of the thumb joints and functional restoring. Ultrasonography can be considered as an accurate and cost effective diagnostic investigation in evaluation of cases with the suspected extensor pollicis longus tendon rupture and tendinosis. This case report shows that technique of EIP to EPL transfer is effective and reliable surgical option

Knowledge and awareness of orthopaedic surgeons about radiation hazards in operation theatres

Background: Due to increase in geriatric orthopaedic patients minimally invasive soft tissue and orthopaedic surgeries are gaining. But such procedures have increased the surgeon’s dependence on fluoroscopy which has exposed them to ever increasing dosage of ionising radiations (both direct and scattered).Methods: The study was carried out among medical professionals attending annual north zone conference of orthopaedics using a pre-designed questionnaire on a non-probability sample of 200 orthopedicians.  Questionnaires contained 11 MCQs.Results: 62% of the surgeons believed that hands receive maximum amount of C-arm radiations followed by thyroid (25%). 9% of surgeons have answered eyes and 4% say gonads. 31% of surgeons believe that 100 mSv is allowable annual effective whole-body dose of radiation. 15% believe it to be 500 msv. Majority (37%) of the surgeons had no idea on the allowable annual effective whole-body dose of radiation. 30% of surgeons believe that allowable annual effective dose of radiation for hands is 50 msv. Further 23% of the surgeons believe it to be 100 msv. 50% have no idea about this.Conclusions: All orthopaedic residents and surgeons should have more information and knowledge about ionising radiation. Special courses and workshops can be arranged at local, regional and national levels in this regard.