Improved Immunohistochemical Detection of Type 1 Insulin-Like Growth Factor Receptor in Human Tumors

The contribution of insulin-like growth factors (IGFs) to cancer biology has been extensively studied in cell lines, revealing that IGFs activate type 1 IGF receptors (IGF-1Rs) to promote cell cycle progression, cell survival, motility and invasion. These findings provoked interest in studying IGF-1R expression in clinical cancers, and in development of drugs that block IGF signaling.

However, there has been striking variation in reported IGF-1R expression in tumors and normal tissues when detected by immunohistochemistry. For example IGF-1R was reported to be unchanged or down -regulated in prostate cancer compared with benign prostate, although since our report of IGF-1R up-regulation at the mRNA and protein level most publications support up-regulation.

This lack of consensus also confounds attempts to interpret results of clinical trials of novel IGF inhibitory drugs. Early trials reported striking clinical responses to IGF-1R inhibition but later trials showed very limited activity in unselected patients. This raises the question as to whether tumor IGF-1R expression correlates with sensitivity to IGF-1R inhibition. Preclinical reports supporting such a link include studies in non-small cell lung cancer.

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Dermatological Aspects of a Humanitarian Mission

Patients with dermatological patholgies represent an important population, especially in developing countries. The cosmetological aspects are important. Objective: To determine the incidence and epidemiology of skin diseases during a humanitarian mission. Methods: 679 patients who presented to our general medical consultations were examined.

Patient data was registered to be analyzed retrospectively. The rare and difficult cases were systematically discussed during the consultation. The patient charts were correlated by the corresponding photos.The ethnic origin of the patients was different. The majority of our patients were younger than 50 years old.

The dermatological problems represented a major motivation to consult, namely itching and skin lesions. The incidence was higher when secondary findings and complaints were also considered. Besides scabies, mycosis and tropical pathologies, the problems of scarring represented a major cosmetological demand.

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Rationales for a Multi-Epitope Approach in an Autologous Renal Cell Cancer Tumor Vaccine

Renal cell carcinoma is an orphan disease with an incidence of less than 1.6:10.000. The median age of patients at primary diagnosis is 60 years and the male to female ratio is 3:2. Until now only a 1997 initiated prospective randomized phase-III trial showed a significant effect in overall survival after radical nephrectomy accompanied by treatment with an autologous renal tumor cell vaccine.

Furthermore, by comparing data from a compassionate use program with a historical group of patients observed for more than 10 years and treated by radical nephrectomy, May et al. demonstrated the same significant effect on the overall survival (42.3 months) for T3 tumors.

Discussions on common tumor markers or tumor associated antigens (TAA) as potential targets for immunotherapy are ongoing especially since authorities like the EMA and the FDA request additional information about the potency and potential risks of these autologous applied antigens.

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Eph/Ephrin-mediated Mesenchymal Stem Cell Regulation of T-cell Activation and Function

Mesenchymal stem cells (MSC) are self-renewing stem cells identified in rodent and human bone marrow aspirates based on their ability to form adherent clonogenic clusters (CFU-F; colony forming units-fibroblastic) in vitro, and by their capacity to differentiate into multiple specialized mesodermal cell lineages.

Similar MSC-like populations have been described in various tissues with different growth and differentiation potentials. These MSC-like populations share a common immunophenotype based on the cell surface expression of various markers, but not limited, to STRO-1, CD73, CD105, CD106, CD90, CD146 and CD166, while lacking expression of CD34, CD3, CD14, CD19, CD31, CD34, CD45, Glycophorin-A and HLA-DR.

In the last few decades, MSC have generated considerable interest due to their production of cytokines and growth factors, which act as potent mediators of angiogenesis, regeneration of damaged tissues, hematopoiesis and immune cell responses. In particular, the paracrine properties of MSC, makes them highly desirable as potential cellular therapies to treat a variety of immune/inflammatory based diseases and conditions.

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Jatropha Curcas Linn can Reduce the Expression of Hsp70 that will Result in Reduced Errors in Protein Folding and Promotion of Normal Protein Function in Proliferation and Apoptosis

Jatropha curcas Linn as a local plant have phytochemical contents, like anti-inflammatory and cytotoxicity properties of phenolic extract. Leaf of J.curcas contents higher phenolic compound, flavonoid and saponin. Application of different varieties of J.curcas in traditional medicine had been reported.

However, information regarding the bioactive compounds and the therapeutic activities is still lacking. These studies suggest that components from J.curcas may have anticancer function and potentially be useful for prevention and treatment strategies.All organisms respond to heat (heat shock response) by upregulating specific heat shock or stress proteins.

Research over the last decade has shown that increased expression of heat shock protein 70 (Hsp70) plays a role in protein folding errors from denaturised proteins and new protein translation, causing proteins to function abnormally. Multiple hits – multiple steps – multiple stage stressors may experience distress and express Hsp70, among other cellular factors, to inhibit cell proliferation and enhance apoptosis.

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Anti-inflammatory Effects of Kelussia odoratissima in Rats Model of Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease of the joints and other body organs, which 1 % of the human population is affected. RA induced in the fourth and fifth decades of life and in women is more common. Kelussiao doratissima contains compounds such as flavonoids, mainly aggregated in the inflorescence and stems of Kelussia, has anti-inflammatory effects. Present study aimed to investigate the anti-inflammatory effect of Kelussia odoratissima on rheumatoid arthritis induced in Wistar rats.

A total of 30 female Wistar rats using subcutaneous injection of complete Freund's adjuvant has been induced and were randomly divided into five groups containing negative control (no treatment), positive control (receiving indomethacin (3mg/ Kg) and three rheumatoid arthritis group receiving three different doses (100,200and 300mg/kg) of hydroalcoholic Kelussia odoratissima extract. material injection were tested in the animals for 10 days.

The symptoms of Rheumatoid arthritis were evaluated according to standardized scoring method at paw and double-blind for the different categories daily. CRP levels were measured and Data were analyzed using the SPSS statistical program (version 17 for Windows). In all the cases for comparison between different groups, Mann-Whitney U-test was used.

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Solute Carrier Family 6 Member 12 Gene Polymorphisms in Japanese Patients with Aspirin-Exacerbated Respiratory Disease

Aspirin-exacerbated respiratory disease (AERD), so-called aspirinintolerant asthma, is a clinical syndrome characterized by severe asthmatic attacks after ingestion of aspirin and/or nonsteroidal antiinflammatory drugs (NSAIDs). AERD is known to be associated with less atopic tendency, persistent eosinophilic infiltration in the airway mucosa, and a more severe clinical course.

The inhibitory action of aspirin and NSAID on cyclooxygenase activity may cause diversion to the 5-lipoxygenase pathway, leading to the overproduction of cysteinyl leukotrienes (LTs). A general consensus exists that increased levels of cysteinyl LTs are key inflammatory mediators in AERD.

However, a study of Japanese asthmatic patients demonstrated that prostaglandin D2 was overproduced during aspirin-intolerant bronchoconstriction, and the urinary concentrations of LTE4 and metabolites of prostaglandin D2 correlatively increased during the reaction.

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Composition and Variation Analysis of the TCR -Chain CDR3 Repertoire in Systemic Lupus Erythematosus Using High-Throughput Sequencing

Sui et al. used a combination of multiplex-PCR, Illumina sequencing and IMGT/High V-QUEST for a standardized analysis of the characteristics and polymorphisms of the T-cell receptor β chain Complementarity-Determining region 3 (TCRβ CDR3) genes in T cells from Systemic Lupus Erythematosus (SLE) patients and healthy donors (NC). However, there are several issues which warrant further consideration. Herein, we will discuss this topic.

It’s honoured to provide a brief commentary on the brilliant study of Sui et al. concerning the T cell immune repertoire sequencing (IRSEQ). IR-SEQ refers to a method to evaluate the diversity of immune system by amplifying the Complimentary Determining Region (CDR) of B-cell Receptor (BCR) or T-cell Receptor (TCR) using multiple-PCR or 5'RACE methods, followed by high-throughput sequencing, which can be used to investigate the association between immune repertoire and diseases.

The authors found that there were more expanded clones and more restricted T-cell repertoire in the SLE group compared to the NC group. Also, SLE patients showed different usage frequencies of TRBV and TRBJ segments compared to NC group. 

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DFTD | A Contagious Fatal Cancer that Threatens the Tasmanian Devils

The Tasmanian devil (Sarcophilus harrisii), similar to its infamous animated cartoon character, Taz, is a ferocious carnivore with a notoriously short temper and little patience. However, future survival of Tasmanian devils in the wild is endangered by a fatal cancer disease that has wiped out ~60% of Tasmanian devils within just two decades.

The fact that Tasmanian devils are prone to a bizarre type of contagious facial cancer disease was first noted in 1996 in the far north east of Tasmania, and since then, the disease has spread south and west and now affects devils in over 85% of their distribution territory.

The disease, termed devil facial tumor disease (DFTD), is spread by biting, causing the appearance of tumors on the face, jaws and in the oral cavity. The tumors often become very large and in ~60% of the cases, metastasize to internal organs, including regional lymph nodes, lungs, spleen, heart and kidneys. The tumors kill the host within 6 months of the emergence of first lesions, due to starvation, secondary infection and metastases formation.

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Monocyte-Induced Prostate Cancer Cell Invasion is Mediated by Chemokine ligand 2 and Nuclear Factor-?B Activity

Prostate cancer is the most common malignancy in American men and metastases are responsible for most prostate cancer mortality. Cancer metastasis is a multistep process in which the tumor microenvironment plays a role to promote aggressive cancer cell behavior. Inflammatory stimuli, especially involving macrophages and their accompanying cytokines are increasingly recognized factors that can promote cancer progression, but how this occurs is not fully understood.

Tumor-associated macrophages (TAM) and stromal cells may support tumor progression by promoting angiogenesis, immune suppression or direct effects on tumor cells. Co-cultures of breast cancer cells and monocytes have been shown to express cell-secreted factors which cause paracrine stimulation of tumor growth and progression. Several tumor specific cell-secreted factors have been identified that mediate interactions between cancer cells and monocytes. Paracrine stimulation of prostate cancer cells and monocytes has been hypothesized; however, studies are needed to determine precisely how prostate cancer cells and monocytes crosscommunicate to promote prostate cancer growth and progression.

Several cytokines and chemokines are produced by macrophages in the tumor microenvironment including IL-8, stromal-derived factor-1 (SDF-1) and CCL2. Prostate cancer cells express receptors for these and other chemokines and can respond to stimulation with growth, proliferation and metastasis. Interleukin 8 produced at high levels by prostate cancer cells can promote angiogenesis and androgen independent tumor growth. Prostate cancer cells that express CCL2 have been shown to cause monocyte and osteoclast recruitment with resulting cancer cell growth and survival.

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Factors associated with Synchronous Endometrial and Ovarian Cancer

A 54-year-old perimenopausal woman complained of abnormal uterine bleedings and lower abdominal pain for 6 months. Personal antecedents were smoking, hypertension, chronic obstruction pulmonary disease, obstructive sleep apnea, obesity (BMI 42.7 kg/m²) and nulliparity.The first exploration showed high tumor markers (Ca125 890 UI/ml, Ca19.9 960 UI/ml) and an enlarged uterus with thickened endometrium, but the gynecological examination was unreliable.

A diagnostic hysteroscopy showed an abnormal growth on the entire endometrial cavity with atypical vascularization. Biopsy was consistent with low-grade endometrial adenocarcinoma.The pelvic magnetic resonance (MR) showed a large uterus, occupied by an endometrial carcinoma 4 mm close to theArchives of Inflammation welcomes research submissions on all aspects of inflammation which is an open access, peer-reviewed online journal. The intention is that the journal should reflect both the experimental and clinical aspects of inflammation.

We will facilitate article submission, rapid article quality assurance through 'peer review', article formatting and processing to a final product which will allow high visibility, impact and provoke debate.uterine serosa. There was an invasion to the cervix stromal, a left 20 cm heterogeneous and a hypovascular multiloculated adnexal mass adhered to mesosigma. No ascites or carcinomatosis were found.A computerized tomography (CT) was performed finding a 6 cm solid left renal tumor suspicious of malignancy, and unspecific pelvic and paraaortic lymph nodes.

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Aspirin and Melanoma

Aspirin is known to provide a variety of health benefits including pain relief, heart attack prevention, and possible prevention of several forms of cancer including colon, breast, esophagus, stomach, prostate, bladder, ovary and the deadliest form of skin cancer-melanoma. In the largest study to date aimed to explore melanoma prevention, researchers at Stanford University found a significant association between frequent use of aspirin and melanoma, where aspirin users were less likely to develop melanoma compared to those who did not take aspirin.

Results also showed that the longer individuals took aspirin, the lower their risk of developing skin cancer. Melanoma is a less frequently occurring form of skin cancer compared to other varieties, however is it most fatal if not found early, accounting approximately 75% of all deaths related to skin cancer. Inflammation plays a major role in the development of cancer, and it is speculated that aspirin may prevent melanoma is through its anti-inflammatory effects. There are several hypotheses regarding the action of aspirin in melanoma prevention.

Scientists speculate that aspirin prevents cancer by inhibiting the Cox-2 gene, which controls inflammation, while other investigators hypothesize that aspirin reduce the incidence of cancer by inhibiting platelets, which when activated release factors that encourage cancer growth and development. While non-aspirin NSAIDs also reduce inflammation, they don’t utilize the same pathways that aspirin uses for activation in the body. 

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Prophylactic EBV Vaccines and its Development

Epstein-Barr virus (EBV) is an important global human pathogen found in over 90% of the world’s population. EBV infection usually occurs in young children and causes no or only nonspecific symptoms. However, EBV is the major cause of infectious mononucleosis. EBV is an oncogenic virus associated with various human malignancies of both epithelial and lymphoid origin such as nasopharyngeal carcinoma, a subset of gastric carcinoma (GC), Burkitt’s lymphoma (BL), Hodgkin lymphoma and post-transplant lymphoproliferative disorder (PTLD).

Almost 200,000 cases of EBV-associated malignancies occur each year worldwide. Currently, no vaccine has been licensed to prevent EBV infection or EBV-associated diseases. There is an urgent need for the development of EBV vaccines. Although a vaccine to prevent EBV infection was proposed as long ago as 1973, the development of an EBV vaccine has been agonizingly slow.EBV major envelope glycoprotein gp350 has been widely considered as an attractive candidate for a prophylactic EBV vaccine.

The reason for choosing gp350 is that EBV causes infection predominantly by binding gp350 to the CD21 receptor on the surface of B lymphocytes. Numerous studies have demonstrated the efficacy of gp350-based vaccines. Prophylactic EBV vaccines have been evaluated in controlled clinical trials vaccinated adults, children and infants in China with a single dose of vaccinia virus expressing gp350. 

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Prophylactic EBV Vaccines and its Development

Epstein-Barr virus (EBV) is an important global human pathogen found in over 90% of the world’s population. EBV infection usually occurs in young children and causes no or only nonspecific symptoms. However, EBV is the major cause of infectious mononucleosis. EBV is an oncogenic virus associated with various human malignancies of both epithelial and lymphoid origin such as nasopharyngeal carcinoma, a subset of gastric carcinoma (GC), Burkitt’s lymphoma (BL), Hodgkin lymphoma and post-transplant lymphoproliferative disorder (PTLD).

Almost 200,000 cases of EBV-associated malignancies occur each year worldwide. Currently, no vaccine has been licensed to prevent EBV infection or EBV-associated diseases. There is an urgent need for the development of EBV vaccines. Although a vaccine to prevent EBV infection was proposed as long ago as 1973, the development of an EBV vaccine has been agonizingly slow.EBV major envelope glycoprotein gp350 has been widely considered as an attractive candidate for a prophylactic EBV vaccine.

The reason for choosing gp350 is that EBV causes infection predominantly by binding gp350 to the CD21 receptor on the surface of B lymphocytes. Numerous studies have demonstrated the efficacy of gp350-based vaccines. Prophylactic EBV vaccines have been evaluated in controlled clinical trials vaccinated adults, children and infants in China with a single dose of vaccinia virus expressing gp350. 

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Benefits and Limits of Risperidone-Methylphenidate Combination in Child Psychiatry

Methylphenidate (MPH) is the first choice pharmacological drug for the treatment of ADHD because of its well-established activity on hyperactivity and inattention.In child psychiatry, risperidone (RIS) is beneficial in Disruptive Behaviour Disorders (DBD) and Pervasive Developmental Disorders (PDD) among other disorders. These medical indications can effectively treat a number of psychiatric childhood disorders, but the co-morbid forms are, in some cases, resistant to monotherapy.

Thus, although the pharmacological action of psychostimulant and antipsychotic drugs may seem to be the opposite of each other, their combination may be useful in comorbid forms of ADHD, particularly with Conduct Disorders (CD) symptoms or disorder, or PDD and DBD.During the last fifteen years, several publications have reported the benefits observed following associations between psychostimulant and antipsychotic treatment.

Bitherapies seem well-tolerated, and beneficial effects have been even found on appetite and sleep disturbances. However, the offsetting effect of adverse effects are not always obvious and the most recent results show that the psychostimulant does not reduce the effects of antipsychotic medication on sedation, weight and body mass index, metabolic parameters and prolactin levels.

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Tumoricidal Activation of Macrophages using Jatropha curcas Leaf Extract

Biological activities of the methanolic was under study. Leaf extracts that contains methanolic acid of Jatropha curcas showed the highest antioxidant activity. Other research in cytotoxicity assay results indicated the anticancer therapeutic property of the root extract against human colon adenocarcinoma (HT-29) cell line but its cytotoxic effect on human hepatocyte (Chang cell) was high.

Macrophages can be activated to become neoplasticidal by interaction with a substance filled immune modulators. Neoplasticidal macrophages can recognize and destroy neoplastic cells in vitro and in vivo. Although the exact mechanism by which macrophages discriminate between neoplastic and normal cells is unknown, it is independent of neoplastic cell characteristics such as immunogenicity, metastatic potential, and sensitivity to drugs.

Moreover, macrophage destruction of neoplastic cells apparently is not associated with the development of neoplastic cell resistance. Macrophages are found in association with neoplasm in a definable pattern, suggesting that the most direct way to achieve macrophage-mediated neoplasm regression is in situ macrophage activation.

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