Immunolocalization of notch signaling protein molecules in a maxillary chondrosarcoma and its recurrent tumor

Background

Notch receptors are critical determinants of cell fate in a variety of organisms. Notch signaling is involved in the chondrogenic specification of neural crest cells. Aberrant Notch activity has been implicated in numerous human diseases including cancers; however its role in chondrogenic tumors has not been clarified.

Method

Tissue samples from a case of primary chondrosarcoma of the maxilla and its recurrent tumor were examined immunohistochemically for Notch1-4 and their ligands (Jagged1, Jagged2 and Delta1) expression.

Results

Both primary and recurrent tumors were histopathologically diagnosed as conventional hyaline chondrosarcoma (WHO Grade I). Hypercellular tumor areas strongly expressed Notch3 and Jagged1 in spindle and pleomorphic cells suggesting up-regulation of these protein molecules at sites of tumor proliferation. Expression patterns were distinct with some overlap. Differentiated malignant and atypical chondrocytes demonstrated variable expression levels of Jagged1, and weak to absent staining for Notch1, 4 and Delta1. Protein immunolocalization was largely membranous and cytoplasmic, sometimes outlining the lacunae of malignant chondrocytes. Hyaline cartilage demonstrated a diffuse or granular precipitation of Jagged1 suggesting presence of soluble Jagged1 activity at sites of abnormal chondrogenesis. No immunoreactivity for the other Notch members was observed. Calcified cartilage was consistently Notch-negative indicating down-regulation of Notch with cartilage maturation. Stromal components namely endothelial cells and fibroblasts variably expressed Notch1, 3 and Jagged1 but were mildly or non-reactive for the other members.

Conclusions

Results indicate that Notch signaling pathway may participate in cellular differentiation and proliferation in chondrosarcoma. Findings implicate Notch3 and Jagged1 as key molecules that influence the differentiation and maturation of cells of chondrogenic lineage.     

Valuable Radiographic Tool for Odontogenic Jaw Keratocyst Diagnosis and Surgical Planning

Objective:

To investigate the clinical use of cone beam computed tomography in the diagnosis of patients with odontogenic jaw keratocyst and to guide computer-aided surgical treatment planning.

Methods:

Imaging, image processing, and visualization technologies were used to produce clear diagnosis, provide proper treatment, and formulate favourable prognosis. Cone beam computed tomography was used to collect medical information including site, extent, shape, and other characteristic features of a patient with large odontogenic jaw keratocyst.

Results:

The imaging technique produced excellent results in imaging, image processing and threedimensional (3D) visualization.

Conclusion:

The 3D digital reconstruction model of the odontogenic jaw keratocyst was shown intuitively.     

Brucine Inhibits Bone Metastasis of Breast Cancer Cells by Suppressing Jagged1/Notch1 Signaling Pathways

Objective: To examine the effects of brucine on the invasion, migration and bone resorption of receptor activator of nuclear factor-kappa B ligand(RANKL)-induced osteoclastogenesis. Methods: The osteoclastogenesis model was builded by co-culturing human breast tumor MDA-MB-231 and mouse RAW264.7 macrophages cells. RANKL(50 ng/m L) and macrophage-colony stimulating factor(50 ng/m L) were added to this system, followed by treatment with brucine(0.02, 0.04 and 0.08 mmol/L), or 10 μmol/L zoledronic acid as positive control. The migration and bone resorption were measured by transwell assay and in vitro bone resorption assay. The protein expressions of Jagged1 and Notch1 were investigated by Western blot. The expressions of transforming growth factor-β1(TGF-β1), nuclear factor-kappa B(NF-κB) and Hes1 were determined by enzyme-linked immunosorbent assay. Results: Compared with the model group, brucine led to a dose-dependent decrease on migration of MDA-MB-231 cells, inhibited RANKL-induced osteoclastogenesis and bone resorption of RAW264.7 cells(P 0.01). Furthermore, brucine decreased the protein levels of Jagged1 and Notch1 in MDA-MB-231 cells and RAW264.7 cells co-cultured system as well as the expressions of TGF-β1, NF-κB and Hes1(P0.05 or P0.01). Conclusion: Brucine may inhibit osteoclastogenesis by suppressing Jagged1/Notch1 signaling pathways.     

Notch signaling and ghost cell fate in the calcifying cystig odontogenic tumor

Notch signaling is an evolutionarily conserved mechanism that enables adjacent cells to adopt different fates. Ghost cells (GCs) are anucleate cells with homogeneous pale eosinophilic cytoplasm and very pale to clear central areas (previous nucleus sites). Although GCs are present in a variety of odontogenic lesions notably the calcifying cystic odontogenic tumor (CCOT), their nature and process of formation remains elusive. The aim of this study was to investigate the role of Notch signaling in the cell fate specification of GCs in CCOT. Immunohistochemical staining for four Notch receptors (Notch1, Notch2, Notch3 and Notch4) and three ligands (Jagged1, Jagged2 and Delta1) was performed on archival tissues of five CCOT cases. Level of positivity was quantified as negative (0), mild (+), moderate (2+) and strong (3+). Results revealed that GCs demonstrated overexpression for Notch1 and Jagged1 suggesting that Notch1-Jagged1 signaling might serve as the main transduction mechanism in cell fate decision for GCs in CCOT. Protein localizations were largely membranous and/or cytoplasmic. Mineralized GCs also stained positive implicating that the calcification process might be associated with upregulation of these molecules. The other Notch receptors and ligands were weak to absent in GCs and tumoral epithelium. Stromal endothelium and fibroblasts were stained variably positive.     

Hormone Receptors,Her-2/Neu and Chromosomal Aberrations in Breast Cancer

Background

There is a great deal of disparity in the incidence of breast cancer in rural and urban India on one hand and between India and Western population on the other.

Methods

We analysed steroid receptor status in cases of breast cancer in a small sample of patients in armed forces. Infiltrating duct carcinomas of breast recorded histologically in mastectomy specimens in last two years were accessioned in the present study with reference to patient and tumour characteristics.

Result

In contrast to the higher rates reported in western literature, only 33 % of the tumours expressed estrogen receptors (ER) and progesterone receptors (PR), of which 24% were ER positive and 30% PR positive. Negative steroid receptor status did not correlate with presence or absence of metastatic nodes, however it was predominant amongst the high grade infiltrating duct carcinomas in this study. Necrosis and lymphovascular invasion demonstrated an inverse relationship with the ER/ PR reactivity. 70% of the node positive cases expressed Her –2/ Neu, reflecting a higher immunoreactivity in this subset of patients. Aneusomy for chromosomes 1, 11 and 17 was common in node positive cases.

Conclusion

Evaluation of chromosomal aberrations by Fluorescent In Situ Hybridization (FISH) technique correlates well with traditional histological parameters.Key Words: Breast carcinoma, Hormone receptors, Her –2/ Neu     

Common polymorphisms in GSTM1, GSTT1, GSTP1, GSTA1 and susceptibility to colorectal cancer in the Central European population

Background

Central Europe presents with the highest incidence of sporadic colorectal cancer (CRC) worldwide. As sporadic CRC represents a typical multifactorial disease, it is characterized by intense interaction of the genetic background with the environment. Glutathione S-transferases could act as attractive susceptibility genes for CRC, as they are directly involved in conjugation between glutathione and chemotherapeutics, environmental pollutants and a wide spectrum of xenobiotics.

Methods

In this study, we investigated associations of polymorphisms in glutathione S-transferases (GSTs) genes, that is GSTA1, GSTT1, GSTM1 and GSTP1, with CRC in a total of 197 cases and 218 controls originating from the Czech Central European population. Polymorphisms were assessed by polymerase chain reaction/restriction fragment length polymorphism-based methods, allele-specific multiplex and allelic discrimination by real-time polymerase chain reaction.

Results

None of investigated polymorphisms showed any associations with CRC, with the exception of GSTP1; where the heterozygote genotype Ile105Val was associated with decreased risk of CRC (P = 0.043).

Conclusions

The frequencies observed in our study are in accordance with those from other European Caucasian populations. Based on our studies, examined variability in GST genes is not a major determinant of CRC susceptibility in the Central European population.     

A study on traditional medicinal plants of Uthapuram,Madurai District,Tamilnadu, South India

Objective

To record the medicinal plants of Uthapuram Village, Madurai district, Tamilnadu, South India for the first time and the usage of these medicinal plants to remediate the diseases among the peoples.

Methods

Explorative field trips were made to the village for about twelve months from April 2012 to May 2013 to survey the medicinal plants and collect the information from the villagers.

Results

From this study 52 species of valuable medicinal plants belonging to 36 families were recorded and their ethnomedicinal values were collected from the village peoples.

Conclusion

This study focuses the importance, utilization and conservation of the medicinal plants among the people.     

Glutathione S-Transferase M1 and T1 Gene Polymorphisms Are Not Associated with Increased Risk of Gestational Diabetes Mellitus Development

Aim:

The aim of this study was to investigate whether the glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) gene polymorphisms contributed to development of gestational diabetes mellitus (GDM).

Subjects and Methods:

Fifty women with diagnosis of GDM and 50 control individuals without GDM or altered glucose intolerance during their pregnancy were enrolled in the study. Multiplex polymerase chain reaction-restriction fragment length polymorphism method was applied to determine the GSTM1 and GSTT1 gene polymorphisms. Genotypes were determined according to bands detected with the agarose gel electrophoresis.

Results:

The difference in the frequencies of GSTM1 null genotypes between GDM and control groups was not statistically significant (60% and 54%, respectively). There was no statistically significant difference between GDM and control groups with respect to GSTT1 null genotype rates (22% and 20%, respectively).

Conclusion:

This study shows no association between GST gene polymorphisms and GDM.     

Time of foaling in Arabian mares raised in Tiaret,Algeria

Objective

To enhance effectiveness of reproduction management in Arabian mares, factors influencing the time of foaling were investigated in this study.

Methods

Data were collected at the National Haras of Tiaret in Algeria from 2003 to 2010. The foaling time of 255 Arabian pure bred mares, aged from 3 to 20 years were used for this study.

Results

A total of 78.07% of foaling happens between 7 pm and 6 am.

Conclusions

The influence of the month of foaling and the sex of the foal, on the time of foaling was statically significant.     

Long survival of primary diffuse leptomeningeal gliomatosis following radiotherapy and temozolomide: case report and literature review

Objective

Primary diffuse leptomeningeal gliomatosis (PDLG) is a rare neoplasm with a short survival time of a few months. there is currently no standardized therapeutic approach for PDLG.

Materials and methods

We report on a 53-year-old male patient who presented with epileptic seizures, gait disturbance, paraparesis and sensory deficits in the dermatomes T8-10.

Results

Magnetic resonance imaging (MRI) revealing numerous spinal and cranial gadolinium-enhancing nodules in the meninges and histopathology led us to diagnose primary diffuse leptomeningeal gliomatosis with WHO grade III astrocytic cells. Consecutively, the patient underwent craniospinal radiotherapy (30 Gy) and 11 sequential cycles of temozolomide. This regimen led to partial tumor regression. Thirteen months later, spinal MRI revealed tumor progression. Second-line chemotherapy with 5 cycles of irinotecan and bevacizumab did not prevent further clinical deterioration. The patient died twenty-two months after diagnosis, being the longest survival time described thus far with respect to PDLG consisting of astrocytic tumor cells.

Conclusions

Radiochemotherapy including temozolomide, as established standard therapy for brain malignant astrocytomas, might be valid as a basic therapeutic strategy for this PDLG subtype.     

Ethnomedicinal plants used in the treatment of skin diseases in Hyderabad Karnataka region,Karnataka, India

Objective

To document traditional medicinal plants knowledge used in treating skin diseases at Hyderabad Karnataka Region.

Methods

The information on the use of medicinal plants in the treatment of skin diseases was gathered from traditional herbal healers and other villagers through interviews.

Results

A total of 60 plants species belonging to 57 genera and 34 families were found useful and herewith described them along with the method of drug preparation, mode of administration, probable dosage and duration of treatment. Several new findings on the traditional rural practices were reported.

Conclusions

The present study revealed that the Hyderabad Karnataka rural people is primarily dependent on medicinal plants for treating skin diseases.     

Neurocognitive sequelae of cerebral malaria in adults: A pilot study in Benguela Central Hospital,Angola

Objective

To characterize the neurocognitive sequelae of cerebral malaria (CM) in an adult sample of the city of Benguela, Angola.

Methods

A neuropsychological assessment was carried out in 22 subjects with prior history of CM ranging from 6 to 12 months after the infection. The obtained results were compared to a control group with no previous history of cerebral malaria. The study was conducted in Benguela Central Hospital, Angola in 2011.

Results

CM group obtained lower results on the two last trials of a verbal learning task and on an abstract reasoning test.

Conclusions

CM is associated to a slower verbal learning rate and to difficulties in the ability to discriminate and perceive relations between new elements.     

Renin,endothelial no synthase and endothelin gene expression in the 2Kidney-1clip goldblatt model of long-term renovascular hypertension

Objective

Numerous reports have shown the influence of renin, nitric oxide (NO) and the endothelin (ET) systems for regulation of blood pressure and renal function. Furthermore, interactions between these peptides have been reported. Aim of our study was to investigate the relative contribution of these compounds in long-term renovascular hypertension/renal ischemia.

Methods

Hypertension/left-sided renal ischemia was induced using the 2K1C-Goldblatt rat model. Renal renin, ET-1, ET-3 and endothelial NO synthase (eNOS) gene expression was measured by means of RNAse protection assay at different timepoints up to 10 weeks after induction of renal artery stenosis.

Results

Plasma renin activity and renal renin gene expression in the left kidney were increased in the clipped animals while eNOS expression was unchanged. Furthermore, an increase in ET-1 expression and a decrease of ET-3 expression was detected in early stenosis.

Conclusions

While renin is obviously involved in regulation of blood pressure and renal function in unilateral renal artery stenosis, ET-1, ET-3 and endothelium derived NO do not appear to play an important role in renal adaptation processes in long-term renal artery stenosis, although ET-1 and ET-3 might be involved in short-term adaptation processes.     

The aflatoxin B1 isolating potential of two lactic acid bacteria

Objective

To determine lactic acid bacteria''s capability to enhance the process of binding and isolating aflatoxin B1 and to utilize such lactic acid bacteria as a food supplement or probiotic products for preventing absorption of aflatoxin B1 in human and animal bodies.

Methods

In the present research, the bacteria were isolated from five different sources. For surveying the capability of the bacteria in isolating aflatoxin B1, ELISA method was implemented, and for identifying the resultant strains through 16S rRNA sequencing method, universal primers were applied.

Results

Among the strains which were isolated, two strains of Lactobacillus pentosus and Lactobacillus beveris exhibited the capability of absorbing and isolating aflatoxin B1 by respectively absorbing and discharging 17.4% and 34.7% of the aforementioned toxin existing in the experiment solution.

Conclusions

Strains of Lactobacillus pentosus and Lactobacillus beveris were isolated from human feces and local milk samples, respectively. And both strains has the ability to isolate or bind with aflatoxin B1.     

Parathyroid Neoplasms: The Army Hospital (Research & Referral) Experience

Background

Neoplasms of the parathyroid are common but parathyroid carcinoma is exceptionally rare. In contrast to most other malignant endocrine tumours that are usually less hormonally active, malignant parathyroid tumours are hyper functional. Malignant parathyroid tumours pose a diagnostic dilemma for the pathologist.

Objective

To study the clinicopathological profile of a case series of parathyroid neoplasms and determine features which facilitate a malignant diagnosis.

Methods

A retrospective analysis of seven cases of surgically treated parathyroid tumours over a three-year period at a single centre was done. Clinical, haematological, biochemical, and radiological data was accrued from medical records. The histopathology slides were reviewed along with the clinicopathological profile in an attempt to delineate markers of malignancy.

Results

Patients ranged from 30 to 58 years of age. Males and females were approximately equal. Weakness and bone pain were the commonest presenting symptoms. Over 50% had significant hypercalcaemia and all had elevated serum parathormone. Clinically apparent mass was seen in only one. All tumours were successfully localised using CT scan and MRI. Thick fibrous capsule and broad septal fibrosis was seen in both the carcinomas; these were thin in the adenomas. Mitotic counts of 1-3 per high power field (HPF), capsular invasion and nodal metastasis were noted in the malignant tumours.

Conclusion

Elevated serum calcium and parathormone values point to a parathyroid neoplasm. Current imaging modalities are successful in localising the tumour preoperatively. Markedly elevated serum calcium, broad fibrous bands, mitotic counts and capsular invasion are indicators of malignancy.Key Words: Parathyroid, Adenoma, Carcinoma     

Twenty-seven years follow-up of a patient with congenital retinocephalofacial vascular malformation syndrome and additional congenital malformations (Bonnet-Dechaume-Blanc syndrome or Wyburn-Mason syndrome)

Purpose

Follow-up of vascular changes in a patient with congenital retinocephalofacial vascular malformation syndrome.

Methods

MRI and cerebral angiography.

Results

In a 36-year-old man, magnetic resonance im aging of the skull and cerebral angiography revealed left intracranial arteriovenous malformations. Follow-up observation of 27 years revealed no essential change of retinal and cerebral arteriovenous malformations. Additional congenital deficits in this patient were described.

Conclusion

Patients with retinal arteriovenous malformations should be early examined with neuroradiological methods.