Cancer Biology

A. Pakdaman developed the first process to enrich water with oxygen to 60 mg O 2 /l. In 1988 he introduced oral oxygen therapy into the clinical medicine and nutrition. Pakdaman's process uses an ion physical linkage of molecular O 2 and H 2 O molecules. The O 2 molecules lodge themselves in the "voids" formed between the H 2 O molecules, which are covered with a protective water membrane. Direct contact with mitochondria cell tissues (glands, intestine, liver, kidney, brain, heart, etc) ruptures the sealing membrane and the released oxygen is then readily available to the cell. Oxygen will be mostly absorbed by diffusion and osmosis through cells in the stomach and intestine and will enter the body's blood circulation system through the portal vein. Such additional oxygen can perform all the same functions as the oxygen absorbed through the lungs. Several structures of our organs participate in the absorption and transportation of the oxygen. Among them are the villi and cells containing mitochondrion in the small intestine as well as the lymph system. One of the many pollutants in our ground, surface and drinking water is Nitrate (NO 3). Bacteria in the water will reduce the nitrate to nitrite, which in turn can evolve into e.g. nitrosamines, a known cancer causing substance. Especially vulnerable are small children, who can suffer from hemoglobin blockages. The oxygen in the water can drastically reduce the levels of nitrate and 1992 tests by the Hygiene Institute of the University of Düsseldorf have shown that oxygen enriched water can reduce nitrate by up to 500%. Scientifically confirmed effects of oxygen on the human body (are): • Improved oxygen utilisation disorder and cellular hypoxia (oxygen starvation); • Correction of hypoventilation due to functional weakness of the respiratory tract, by virtue of oxygen transport directly into the blood circulation via the gastrointestinal tract and portal vein; • Correction of disorders of intracellular respiration caused by anemia, enzyme defect, poisoning etc; • Conversion of anaerobic metabolism in cancer cells, inhibiting the growth of malignant cells; • Prophylactic and therapeutic improvement of migraine due to reduction of cerebral hypoxia; • Immune system stimulation and modulation: leucocytes, monocytes, granulocytes, natural killer cells; • Elevation of cellular energy delivery and increases in physical and psychological ability; • Improvements of cell metabolism and biological oxidation through increased availability of oxygen for the mitochondrion and also influencing the regulation of cellular calcium ion concentration; • Acceleration of body detoxification via activation of cytochrome P-450 in the liver; • Improvements of the micro-circulation in the capillary blood vessels; • Improvement of myocardial hypoxia and prevention of heart tissue necrosis insufficiency; • Regulation of blood pressure through effects on chemo-receptors in the carotid and aortic bodies; • Increased number of blood cells; erythrocytes, Hct, Hb and platelets; • Antibacterial and antiviral effect, especially on anaerobic bacteria; • Cytotoxic effect on camphylobactor pylori, plus other gastric and intestinal mucosa improvements; • Neutralization of the stomach acids secreted by the parietal cells and transformation into water; • Acceleration of the wound-healing process (washing and cleansing of open wounds).

Combinatorial strategy has been used in therapeutic angiogenesis in animal models of peripheral arterial disease (PAD) and coronary artery disease for decades. Previous studies have shown that basic fibroblast growth factor (FGF-2) and platelet-derived growth factor BB (PDGF-BB) proteins together establish functional and stable vascular networks on mouse corneal and also in animal model of hindlimb ischemia. However, the short half life of protein by single injection is not sufficient to achieve effective dosage, repeated and prolonged injection causes systemic toxicity. Here we study the synergistic effects of FGF-2 and PDGF-BB by intramuscular injection of naked plasmid DNA on therapeutic angiogenesis in rabbit model of hindlimb ischemia. We found that transient delivery of FGF-2 and PDGF-BB naked DNA together resulted in greater increases in capillary growth, collateral formation and popliteal blood flow compared with control and single gene delivery. Our data provided novel evidence of beneficial effects of DNA-based FGF-2 and PDFG-BB on muscle repair after ischemic injury. These findings reveal an alternative therapeutic approach in the treatment of ischemic diseases and even in muscular disorders.

A chronic continuous or intermittent gastrointestinal tract dysfunction, the irritable bowel syndrome (IBS), appears to be due to dysregulation of brain-gut-microbiota communication. Furthermore, the "microbiota" greatly impacts the bi-directional brain-gut axis communication. This article describes IBS in relation to similar diseases, presents the background to osteopathy, and proposes osteopathic manipulative treatment (OMT) to manage IBS. In IBS, OMT focuses on the nervous and circulatory systems, spine, viscera, and thoracic and pelvic diaphragms in order to restore homeostatic balance, normalize autonomic activity in the intestine, promote lymphatic flow, and address somatic dysfunction. Lymphatic and venous congestion are treated by the lymphatic pump techniques and stimulation of Chapman's reflex points. A simple treatment plan designed to lessen chronic pain and inflammation in IBS is presented based on current evidence-based literature. Since food itself, food allergies, and intolerance could contribute to symptom onset or even cause IBS, this article also provides dietary modifications to consider for patients.

Tumor microenvironment (TME) is a host for a complex network of heterogeneous stromal cells with overlapping or opposing functions depending on the dominant signals within this milieu. Reciprocal paracrine interactions between cancer cells with cells within the tumor stroma often reshape the TME in favor of the promotion of tumor. These complex interactions require more sophisticated approaches for cancer therapy, and, therefore, advancing knowledge about dominant drivers of cancer within the TME is critical for designing therapeutic schemes. This review will provide knowledge about TME architecture, multiple signaling, and cross communications between cells within this milieu, and its targeting for immunotherapy of cancer.

Prostate cancer characteristically induces osteoblastic bone metastasis, for which no therapies are available. A dual kinase inhibitor of c-Met and VEGFR-2 (cabozantinib) was shown to reduce prostate cancer growth in bone, with evidence for suppressing osteoblastic activity. However, c-Met and VEGFR2 signaling in osteoblasts in the context of bone metastasis remain unclear. Here we show using cultured osteoblasts that hepatocyte growth factor (HGF) and VEGF-A increased receptor activator of NFkB ligand (RANKL) and M-CSF, two essential factors for osteoclastogenesis. Insulin-like growth factor-1 (IGF1) also increased RANKL and M-CSF via c-Met transactivation. The conditioned media from IGF1-, HGF-, or VEGFA-treated osteoblasts promoted osteoclastogenesis that was reversed by inhibiting c-Met and/or VEGFR2 in osteoblasts. In vivo experiments used cabozantinib-resistant prostate cancer cells (PC-3 and C4-2B) to test the effects of c-Met/VEGFR2 inhibition specifically in osteoblasts. Cabozantinib (60 mg/kg, 3 weeks) suppressed tumor growth in bone and reduced expression of RANKL and M-CSF and subsequent tumor-induced osteolysis. Collectively, inhibition of c-Met and VEGFR2 in osteoblasts reduced RANKL and M-CSF expression, and associated with reduction of tumor-induced osteolysis, suggesting that c-Met and VEGFR2 are promising therapeutic targets in bone metastasis.

Ilmiah Divisi Neuro-Onkologi Departemen Bedah Saraf RSUD Dr. Soetomo-FK UNAIR 2 28.1 Introduction & Epidemiology  Medulloblastoma (MB) & atypical teratoid/rhabdoid tumors (AT/RT)  1 st children < 4 yo & 2 nd adolescents up to 19 yo.  Characteristics : malignant, undifferentiated cell morphology and disseminate throughout the CNS.  The most embryonal brain tumor, 10% of all pediatric brain tumor & the most common malignant childhood posterior fossa tumor.

To evaluate the difference between pre- and post-menopausal breast cancer regarding menstrual and reproductive risk factors The case-control study was conducted in Mayo Hospital, Lahore, between October 2008 and April 2009. Cases were breast cancer patients admitted in the surgical and oncology floors of the hospital. Controls were hospital patients without breast cancer. The study enrolled 150 cases and 300 controls. Menstrual and reproductive history was taken from both the cases and the controls. For every risk factor age-adjusted odds ratio (OR) and 95% confidence interval (CI) was calculated by logistic regression analysis, separate for pre- and post-menopausal women. Among the breast cancer patients, 42.7% were pre-menopausal and 57.3% were post-menopausal. Age at menarche had no association with breast cancer for both pre- and post-menopausal women. Nulliparity was a risk factor for both pre-menopausal (OR 4.1, 95% CI 1.4-12.6) and post-menopausal breast cancer (OR 8.2, 95% C...

Diarrhea is a common side effect of chemotherapy regimens. Diarrhea can cause depletion of fluids and electrolytes, malnutrition, and dehydration. Chemotherapy-induced diarrhea (CID) can occur in as many as 50-80 percent of patients receiving chemotherapy. Probiotics have been shown effective at preventing diarrhea in inflammatory bowel disease and may prove useful in the oncology setting, Clinical research indicates that probiotics promote a healthy balance of intestinal flora and has immunomodulatory effects in cancer patients and may help minimize some of the negative gastrointestinal side effects associated with treatment. This article reviews the current available scientific literature regarding the effect of Floralite capsules in promoting immune function & As supportive therapy for chemotherapy induced diarrhea.

Nimotuzumab (h-R3) is a humanized anti-epidermal growth factor receptor monoclonal antibody (mAb) registered for treating head and neck tumours. The present study was designed to evaluate the systemic and skin toxicity of chronic intravenous administration of the h-R3 in a relevant species demonstrated by comparing the h-R3 binding affinity constants (Kd) in microsomal placental fractions from Homo sapiens and Cercopithecus aethiops monkeys using an EGF-Receptor radioligand competition assay. The Kd obtained for Nimotuzumab were 9.1 x 10 -8 M for monkeys and 4.5 x 10 -8 M for humans. Monkeys (n = 18) were distributed into three groups with three animals of each sex in each group. Group I received saline; group II received 2.85 mg/kg of h-R3; and group III received 28.57 mg/kg of the h-R3, which represent 1 and 10 times the human dose, and they were weekly intravenously treated during 26 weeks. During the study there were no deaths. Electroneurophysiological, sanguine chemistry and haematological results did not evidence alterations. Areas of haematomas, probably related with the administration procedure, were observed at the administration zones of all animals. The electrocardiography study showed at the end of the study a slight increase in the cardiac frequency of four treated animals without other signs. Unexpectedly, skin biopsies and a detailed clinical inspection of the animals did not detect the presence of cutaneous rash or any other skin toxicity sign reported for the majority of the anti-EGF-R monoclonal antibodies. It is concluded that doses up to 28.5 mg/kg of h-R3, intravenously administered during 26 weeks to Cercopithecus aethiops monkeys, do not produce considerable toxic effects. © 2 0 0 8 L A N D E S B I O S C I E N C E .

Oral submucous fibrosis (OSMF) is a potentially malignant disease that results in progressive juxtaepithelial fibrosis of the oral soft tissues, resulting in increasing loss of tissue mobility , marked rigidity and an eventual inability to open the mouth. The treatment of oral submucous fibrosis includes iron, multivitamins including lycopene, spirulina, pentoxifyl-line, local submucosal injections of steroids, hyaluronidase and chylomicrons, aqueous extract of healthy human placenta, and surgical excision of the fibrous bands.

The purpose of this study was to understand the perception of oncology nurses and how it is related to cancer rehabilitation in Korea. A qualitative study with three focus groups consisting of 6-8 Korean oncology nurses (n = 21) was conducted. The interviews were thematically analyzed. Two main themes for the attributes of cancer rehabilitation were "comprehensive activities of nurses" and "active involvement of survivors." Six subthemes from the oncology nurses' care experiences were identified:"incorporating partnership and sharing feelings," "fulfilling individualized needs," "providing timely and practical support," "enhancing internal strength with optimistic mindset," "regaining functional independence," and "getting family members in." The findings suggest that oncology nurses can play a key role in rehabilitation for cancer survivors. Nursing interventions focused on comprehensive activities of nurses as well as active involvement of survivors can be effective in enhancing cancer survivors' strength and resilience in order to lead a healthy life. Oncology nurses need to be taught a psychosocial intervention based on individualized assessment and family partnership for cancer survivors.

A series of novel pyridazinone derivatives bearing benzenesulfonamide moiety (2aeh) has been synthesized by the condensation of appropriate aroylacrylic acid and 4-hydrazinobenzenesulfonamide hydrochloride in ethanol. Five derivatives (2a, 2b, 2d, 2g and 2h) were evaluated for their anticancer activity toward human cancer cell lines by the National Cancer Institute. The 2h showed remarkable activity against SR (leukemia) and NCI-H522 (non-small cell lung) with a GI 50 value of less than 0.1 mM. It also displayed good activity against leukemia (CCRF-CEM, HL-60 (TB), K-562, MOLT-4, RPMI-8226), nonsmall cell lung cancer (NCI-H460), colon (HCT-116, HCT-15, HT29, KMI2, SW-620), CNS (SF-295), melanoma (MALME-3M, M14, MDA-MB-435 SK-MEL-5), ovarian (OVCAR-3, NCI/ADR-RES) and breast (MCF7) cancer cell lines with a GI 50 less than 1.0 mM. The acute toxicity study of 2h indicated that it is well tolerated intra-peritoneally (400 mg/kg) by athymic nude mice. The 2h may possibly be used as lead compound for developing new anticancer agents.

The global burden of cancer as a public health problem cannot be overemphasized. In the developed countries, Cancer is fast growing out of the reach of trained oncologists and other experts. The burden of the problem is not limited to the developed countries; but recent reports showed that cancer is now a leading cause of morbidity and mortality in resource-constrained developing countries thus making it a major health priority. There is growing need to itemize these challenges to cancer care delivery in such resource-limited settings as a matter of urgency, with the view to particularly emphasize the creation of cost-effective, rational algorithms utilizing affordable chemotherapeutics to treat curable disease. The delivery of comprehensive cancer care in resource-poor settings demands a concerted effort by a team of multidisciplinary care providers, even if they are not trained oncologists. This article seeks to highlight such challenges in managing cancers in the developing world using Banso Baptist Hospital experience as an example. The communique also suggests ways of improving the care of cancer patients in such settings.

World Cancer Day is an annual occasion on the global calendar that the entire world bands together in the fight against the global cancer epidemic. It takes place every year on 4 February. The day aims to save millions of preventable deaths each year by raising awareness and education about cancer, and pressing governments and individuals across the world to take action against the disease. In Ghana, though the statistics of cancers varies due to lack of well-defined national cancer registry to collate national figures. The few statistics available which is made public appears alarming with a high mortality rate. Though tremendous progress has been made with breast cancer, the mortality rate is not something to take away. The number of men dying from prostate cancer is outrageous based on figures available. Though advances in the diagnosis and treatment of breast cancer are paying off, increased funding could benefit prostate cancer. Recently, the Ghana News Agency

117 Mapping of tp 53 mutations in bone cancers present in COSMIC database to its secondary and tertiary structure with in silico prediction of newly formed HLA binding epitopes as candidates for synthetic peptide vaccine. Mutations in bone cancers present in COSMIC database were listed and manually induced in wt p53 FASTA sequence. Wt p53 secondary structure was predicted. Template identified and tertiary structure of wt p53 was modelled in Cn3D followed by individual mutations mapping onto this model. HLA class I binding affinity was determined for mutated sequences to determine any newly binding peptide sequences. 62 missense mutations were identified. After predicting secondary structure, template was identified as PDB ID 1MZR for tertiary structure modelling. Mutations were highlighted that showed most of mutations in DNA binding region of tp 53 tetramer. Wt p53 had 19 HLA class I binders whereas in 62 mutated sequences we identified 18 neobinders not present in wt sequence. Neoepitopes identified serve as candidates for individualized anti-cancer peptide vaccine therapy.

Cadmium(Cd) is one of the most dangerous occupational and environmental toxins. The objective of the present
study is to examine the potential prophylactic effects of phytic acid (PA) on thyroid hormones of male rats
intoxicated with Cd. The male albino rats were divided into five groups: group I (control) was fed with the basal
diet, group II was intoxicated with Cd in drinking water, groups III, IV, and V were intoxicated with Cd in drinking
water and fed with the diet containing 3.5, 7, and 10 g of PA/kg, respectively. The results indicated that the serum
calcium, iron (Fe), and total Fe binding capacity levels and serum T3 and T4 in Cd-treated rats of group II were
decreased when compared with the control group, while PA-administered groups with Cd showed a significant
improvement when compared with the Cd-treated rats only. Serumthyroid stimulating hormone (TSH) level was
significantly increased in Cd-treated rats compared with the control group, while the addition of PA in diet
decreased the high levels of TSH. These results indicated a prophylactic effect of PA against Cd-induced toxicity
in rats.
Keywords
Cadmium, phytic acid, thyroid, T3, T4, TSH, toxicity

The chemokine stromal cell-derived factor (SDF-1; also known as chemokine ligand 12 [CXCL12]) regulates many essential biological processes, including cardiac and neuronal development, stem cell motility, neovascularization, angiogenesis, apoptosis, and tumorigenesis. It is generally believed that SDF-1 mediates these many disparate processes via a single cell surface receptor known as chemokine receptor 4 (CXCR4). This paper characterizes an alternate receptor, CXCR7, which binds with high affi nity to SDF-1 and to a second chemokine, interferon-inducible T cell chemoattractant (I-TAC; also known as CXCL11). Membrane-associated CXCR7 is expressed on many tumor cell lines, on activated endothelial cells, and on fetal liver cells, but on few other cell types. Unlike many other chemokine receptors, ligand activation of CXCR7 does not cause Ca 2+ mobilization or cell migration. However, expression of CXCR7 provides cells with a growth and survival advantage and increased adhesion properties. Consistent with a role for CXCR7 in cell survival and adhesion, a specifi c, high affi nity small molecule antagonist to CXCR7 impedes in vivo tumor growth in animal models, validating this new receptor as a target for development of novel cancer therapeutics. CORRESPONDENCE Thomas J. Schall: tschall@chemocentryx.com Abbreviations used: CXCL, chemokine ligand; CXCR, chemokine receptor; GPCR, G protein-coupled receptor; HUVEC, human umbilical vein endothelial cell; I-TAC, interferon-inducible T cell α chemoattractant; SDF-1, stromal cell-derived factor.

Abstract
Gastric cancer is the 2nd most common cause of death among all cancers and is the 4th most common cancer
in the world. The number of deaths due to gastric cancer is about 800,000 annually. Gastric cancer is more
common in men as compared to women and is 3rd most common cancer after colorectal and breast cancers in
women. A progressive rise in the incidence rate has been observed in females over the last 5 years. The highest
incidence of stomach cancer is in China, South America and Eastern Europe. The incidence of gastric cancer has
20 fold variation worldwide. Global variation is linked by two factors which play important role in developing
gastric cancer. One is infection with Helicobacter pylori and the 2nd is diet. South Asia is a region with low risk,
despite a high prevalence of H.pylori. Gastric carcinoma is common in southern region of India. Gastric cancer
is more readily treated if diagnosed early. This study aims to provide awareness about gastric cancer as well as
an updated knowledge about risk factors and epidemiology of gastric cancer in Pakistan.

We present a study on whether and to what extent subcellular localization may compete favorably with photosensitization efficiency with respect to the overall efficiency of photoinduced cell death. We have compared the efficiency with which two cationic photosensitizers, namely methylene blue (MB) and crystal violet (CV), induce the photoinduced death of human cervical adenocarcinoma (HeLa) cells. Whereas MB is well known to generate singlet oxygen and related triplet excited species with high quantum yields in a variety of biological and chemical environments (i.e., acting as a typical type II photosensitizer), the highly mitochondria-specific CV produces triplet species and singlet oxygen with low yields, acting mostly via the classical type I mechanism (e.g., via free radicals). The findings described here indicate that the presumably more phototoxic type II photosensitizer (MB) does not lead to higher degrees of cell death compared to the type I (CV) photosensitizer. In fact, CV kills cells with the same efficiency as MB, generating at least 10 times fewer photoinduced reactive species. Therefore, subcellular localization is indeed more important than photochemical reactivity in terms of overall cell killing, with mitochondrial localization representing a highly desirable property for the development of more specific/efficient photosensitizers for photodynamic therapy applications.

With growing advances in the field of science and research, extensive work is being carried out in the area of cancer. A lot of anti-cancer drugs have surfaced over the years. These drugs are evaluated on the basis of their effectivity to adverse effect ratio. In the present study, we have performed docking studies of an Anthraquinone antibiotic, Mitoxantrone (MTX) with its possible targets such as DNA, Human serum albumin (HAS) and Signal transducer and activator of transcription (STAT4) using Autodock 4.2 and Schrodinger software suit. The interaction of MTX with DNA and HSA reveal its affinitive binding to these targets in the nucleus and blood respectively. It was found that partial intercalation of MTX occurs in the major as well as minor groove of the DNA with high preference for the former. Binding energy and docking score of Mitoxantrone to DNA was found to be-2.19 and-9.773 respectively. Docking studies reveal that MTX binds with HSA to a non-classical high affinity site in the domain 1, site III via hydrophobic, electrostatic and hydrogen bonds with a docking score and binding energy of-7.179 and-1.84 respectively. Mitoxantrone binds STAT4 with a high docking score of-5.373 and binding energy of-3.38.

The current review presents an update of drug delivery using poly(ethylene glycol) (PEG), that focuses on recent developments in both protein and organic drugs. Certainly the past 10 years has resulted in a renaissance of the field of PEG drug conjugates, initiated by the use of higher molecular weight PEGs (M . 20,000), especially 40,000 which is estimated w to have a plasma circulating t of approximately 10 h in mice. This recent resuscitation of small organic molecule delivery 1 / 2 by high molecular weight PEG conjugates was founded on meaningful in vivo testing using established tumor models, and  has led to a clinical candidate, PEG-camptothecin (PROTHECAN ), an ester based prodrug currently in phase II trials. Additional applications of high molecular weight PEG prodrug strategies to amino containing drugs are presented: similar tripartate systems based on lower M PEG and their use with proteins is expounded on. The modification of a benzyl w elimination tripartate prodrug specific for mercaptans is presented, and its successful application to 6-mercaptopurine giving a water soluble formulation is discussed. Recent novel PEG oligonucleotides and immunoconjugates are also covered. Clinical results of FDA approved PEGylated proteins are also presented. 

Microspheres are characteristically free flowing powders having particle size ranging from 1-1000 μm consisting of proteins or synthetic polymers. The range of Techniques for the preparation of microspheres offers a Variety of opportunities to control aspects of drug administration and enhance the therapeutic efficacy of a given drug. There are various approaches in delivering a therapeutic substance to the target site in a sustained controlled release fashion. It is the reliable means to deliver the drug to the target site with specificity, if modified, and to maintain the desired concentration at the site of interest. Moreover the microspheres are of micron size so they can easily fit into various capillary beds which are also having micron size. Microspheres received much attention not only for prolonged release, but also for targeting of anticancer drugs. There are various departments of medicine like cancer, pulmonary, cardiology, radiology, gynecology, and oncology etc., numerous drugs are used and they are delivered by various types of drug delivery system. Among them microspheric drug delivery system has gained enormous attention. The purpose of the review is to compile various types of microspheres, different methods to preparation, its applications and also various parameters to evaluate their efficiency.

It has been demonstrated for the first time that a wheat germ extract prevents colonic cancer in laboratory animals. Four-week-old inbred male F-344 rats were used in the study. Colon carcinogenesis has been induced by azoxymethane (AOM). Ten rats served as untreated controls (group 1). For the treatment of the animals in group 2, AOM was dissolved in physiologic saline and the animals were given three subcutaneous injections 1 week apart, 15 mg/kg body weight (b/w) each. In two additional groups Avemar (MSC), a fermented wheat germ extract standardized to 2,6-dimethoxy-p-benzoquinone was administered as a tentative chemo-preventive agent. MSC was dissolved in water and was given by gavage at a dose of 3 g/kg b/w once a day. In group 3, animals started to receive MSC 2 weeks prior to the first injection of AOM daily and continuously thereafter until they were killed 32 weeks later. In group 4 the basal diet and MSC were administered only. At the end of the experiment all the rats were killed by exsanguination, the abdominal large vessels were cut under a light ether anesthesia and a complete autopsy was performed. Percentage of animals developing colon tumors and number of tumors per animals: group 1 -0 and 0; group 2-83.0 and 2.3; group 3 -44.8 (P < 0.001) and 1.3 (P < 0.004), group 4 -0 and 0. All the tumors were of neoplastic nature also histologically. The numbers of the aberrant crypt foci (ACF) per area (cm 2 ) in group 2 were 4.85 while in group 3 the ACF numbers were 2.03 only (P < 0.0001).

Ophiocordyceps sinensis (Berk.) Sung et al. is popularly known as Yarsagumba (winter worm summer grass) in Nepal. It is a well-known entomogenous fungus distributed in alpine nival zone of trans-Himalayas and Tibetan Plateau. Its occurrence in extreme biological niche and cohabitation with insect [Thitarodes (Hepialus)] larvae has led to unique assemblage of metabolites including proteins and nitrogenous compounds, polysaccharides, sterols, nucleosides, fatty acids and their derivatives, vitamins and inorganics. In traditional Chinese medicine, it is one of the most trusted main ingredients for several preparations of remedy from wide range of human health conditions. Several biological activities from O. sinensis have been reported that include anti-inflammatory, antioxidant, antitumor, anti-metastatic, immunomodulatory, antimicrobial, insecticidal, hypolipidaemic, hypoglycemic, anti-ageing, lipolytic, neuroprotective, renoprotective effects, etc. The chemical constituents and their pharmacological uses are reviewed here highlighting the potentiality of this highly esteemed traditional Himalayan medicine.

Therese Schroeder-Sheker founded the palliative medical field of music-thanatology, is an artist and clinician in residence at The Catholic University of America, and directs the Chalice of Repose Project in Oregon. She publishes frequently and may be reached via email at phoebe51@chaliceofrepose.org.

CRISPR / Cas9 is an effective gene-editing technique for treating breast cancer. An estimated 60% of cancer deaths are related to breast cancer. Breast cancer is progressive and aggressive, causing fatalities of one in nine women globally. Treatment is limited, with long-term, harmful side effects. Chemotherapy and radiation therapy are among the treatments currently used. CRISPR / Cas9 is an option for cancer treatments and therapies. It can correct genomic sequences and cut the DNA molecule at specific regions. This review article will discuss various aspects of CRISPR and its role in cancer therapies and treatments. These new tools should replace current treatments used to combat the disease, minimizing side effects and providing a better quality of life for cancer survivors.

Cervical lymphadenopathy is one of the common clinical condition which may be due to various causes like infection(especially tuberculosis in our country), inflammation and malignant conditions. The aim of our study is to evaluate the role and diagnostic utility of ultrasonogram and elastography to differentiate the benign and malignant causes of cervical lymphadenopathy as well as differentiating between various benign causes. Materials & Methods: It is a prospective study of 85 patients having cervical lymphadenopathy using Ultrasonogramand Elastography. Biopsy/ FNAC was done for all cases and the results were compared. Results:The sensitivity and specificity for diagnostic value of sonography in differentiating the malignant nodes from benign nodes were 88.9% and 98.0% respectively and for elastography they were 88.9% and 89.8% respectively. Tuberculous nodes could not be identified separately by elastography due to overlapping features. Conclusion: The real time strain Elastography can distinguish benign and malignant cervical lymph nodes with high sensitivity and specificity, but it is not much useful in differentiating various etiologies in benign or malignant nodes. It can be used as an adjunct tool with sonography in characterising the lymph node and can be included in the initial workup of the patients with cervical lymphadenopathy, so that more malignancy can be brought into light.

Background/Aim: Altered fractionation is an area of intense clinical research in radiation oncology. Estimation of the α/β ratio of individual carcinomas after establishment of primary cell cultures from tumor biopsies may prove of importance in the individualization of radiotherapy schemes. Materials and Methods: Here we proposed a simple method to estimate the α/β ratio in cultured cell lines (two lung carcinomas: A549 and H1299; one lung fibroblast cell line: MRC5), using viability assays. Results: For the A549 cell line, the α/β ratio ranged from 14-25 Gy, for H1299 from 11-43 Gy and for the MRC5 fibroblast cell line this was far lower, ranging from 0.69 to 6 Gy. The α/β ratio decreased when extracted from comparisons of lower dose per fraction schemes. Conclusion: The α/β ratio of a cell line can be easily defined after simple viability/dose fractionation experiments. The molecular biology of radiation-induced cell death remains poorly elucidated. Apoptosis and mitotic catastrophe are the two identified patterns of death after irradiation (1). According to the linear-quadratic model, radiation death results as the contribution of two different components (2). The first one is the direct creation of non-reparable lethal DNA damage (the α/linear component) and the second is the accumulation of non-lethal events (β/exponential component) that become lethal when more than one are combined. Which of the two components is more important strongly depends not only upon the cell and tissue type, but also upon the radiation dose and the quality of the beam. An α/β ratio characterizes each cell type, and reflects the dose in Grays where both components contribute equally to the overall cell lethality. Low α/β values characterize normal cells and tissues (such as fibroblasts and endothelial cells) which are less sensitive to small radiation fractions, while the damage suffered increases rapidly with the increase of the dose per fraction. In contrast, high α/β values are typical of highly proliferating normal cells (such as mucosa and skin epithelium) and the damage induced depends strongly on the total physical dose applied and weakly on the fractionation of the radiation dose (3). Cancer cells and tissues have long been considered to behave like highly proliferating normal cells, therefore being credited with high α/β ratios. This assumption, however, has proven to be incorrect, as radiobiological analysis of clinical data in prostate and breast cancer have shown low α/β values for these common tumors (4, 5). Assays that could provide the α/β values of carcinomas in patients before irradiation would allow the individualization of the fractionation scheme, providing schedules that would be the most appropriate for each patient. In the current study, we sought to characterize the α/β ratio in two human lung cancer cell lines and a fibroblast cell line using simple dose–response experiments and radiobiological analysis of the biological isoeffect dose. This would provide a model for subsequent application in primary cell lines established from patients with cancer.

PURPOSE: The p.P347Q RHO mutation is responsible for almost 30% of the autosomal dominant Retinitis Pigmentosa (adRP) in Minas Gerais (MG) – Brazil. The purpose of this study was to describe: the segregation of the p.P347Q RHO mutation in 6 unrelated families from the small isolated city of Tabuleiro-MG; the haplotype reconstruction; and the clinical characteristics of the p.P347Q allele. METHODS: Visual acuity, retinography, autofluorescense and OCT were performed on 23 patients, and full-field ERG on 6 patients. Blood samples were collected on 23 patients (17 affected and 6 non-affected, ranging from 2 to 61 years old). Three probands were sequenced using a targeted capture panel including 224 known retinal disease genes. Next-generation sequencing (NGS) data was then aligned, processed and filtered against control datasets using an in-house custom pipeline. Identification of p.P347Q from NGS data in each of the unrelated probands was validated through Sanger sequencing. DNA samples of the probands' parents and additional unrelated individuals linked to Tabuleiro were then collected and Sanger sequenced for the presence of p.P347Q. Informative captured SNPs were used to infer haplotypes across each of these individuals. RESULTS: A C to A transversion at position 1040 (p.P347Q) of the cDNA has been identified in all 12 RP individuals currently sequenced for the variant. All individuals with this mutation had early-onset night blindness and substantial visual field losses as teenagers. All patients who underwent full field ERG testing demonstrated non-recordable ERGs. Autofluorescence retinography showed maculopathy and a hipoautofluorescent ring around the optic disc in all patients. Lastly, on the basis of conserved haplotypes linked to this pathogenic variant, we propose that p.P347Q spread through a cohort of geographically isolated families by a preceding founder effect. CONCLUSIONS: The p.P347Q allele represents a founder mutation causing a rapidly progressive form of adRP in our distinct population. The identification of this founder effect and subsequent mutation may greatly simplify the molecular diagnosis of