Vaccination with irradiated autologous tumor cells engineered to secrete granulocyte-macrophage colony-stimulating factor augments antitumor immunity in some patients with metastatic non-small-cell lung carcinoma.

PURPOSE: We demonstrated that vaccination with irradiated tumor cells engineered to secrete granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulates potent, specific, and long-lasting antitumor immunity in multiple murine models and patients with metastatic melanoma. To test whether this vaccination strategy enhances antitumor immunity in patients with metastatic non-small-cell lung cancer (NSCLC), we conducted a phase I clinical trial. PATIENTS AND METHODS: Resected metastases were processed to single-cell suspension, infected with a replication-defective adenoviral vector encoding GM-CSF, irradiated, and cryopreserved. Individual vaccines consisted of 1 x 10(6), 4 x 10(6), or 1 x 10(7) cells, depending on overall yield, and were administered intradermally and subcutaneously at weekly and biweekly intervals. RESULTS: Vaccines were successfully manufactured for 34 (97%) of 35 patients. The average GM-CSF secretion was 513 ng/10(6) cells/24 h. Toxicities were restricted to grade 1 to 2 local skin reactions. Nine patients were withdrawn early because of rapid disease progression. Vaccination elicited dendritic cell, macrophage, granulocyte, and lymphocyte infiltrates in 18 of 25 assessable patients. Immunization stimulated the development of delayed-type hypersensitivity reactions to irradiated, dissociated, autologous, nontransfected tumor cells in 18 of 22 patients. Metastatic lesions resected after vaccination showed T lymphocyte and plasma cell infiltrates with tumor necrosis in three of six patients. Two patients surgically rendered as having no evidence of disease at enrollment remain free of disease at 43 and 42 months. Five patients showed stable disease durations of 33, 19, 12, 10, and 3 months. One mixed response was observed. CONCLUSION: Vaccination with irradiated autologous NSCLC cells engineered to secrete GM-CSF enhances antitumor immunity in some patients with metastatic NSCLC.     

Depression in women--issues in evaluation and management

Depression is probably the most common psychiatric disorder in women. Women are a vulnerable group of depression due to psychological, social and biological factors. Marital relationships, social support, roles and self esteem are factors that contribute to depression. In addition, several periods in women's life relating to the reproductive cycle are periods of increased vulnerability. Management of depression in women should consist of detailed assessment of all the above factors. Drug treatment of depression in women requires an in depth understanding of pharmacokinetics of the drugs used and possible drug interactions. Treatment of depression in women should integrate both psychosocial and biological treatment modalities.     

Angiogenesis during tumor progression in the oral cavity is related to reduced apoptosis and high tumor cell proliferation

Angiogenesis, the growth of new blood vessels, is believed to aid tumor progression and metastasis. Tumor progression is also influenced by the extent of proliferation and apoptosis. This study, therefore, analyzed in lesions of the oral cavity, the significance of angiogenesis in relation to apoptosis, expression of apoptosis regulatory p53, bax and bcl-2 proteins as well as tissue proliferation defined by cyclin D1 expression. Results from this study suggest that angiogenesis increases as histological abnormality increases in the oral mucosa. The expression of apoptosis regulatory proteins also appears to be altered in a histologically dependent manner. The correlation seen between CD34 expression, cyclin D1 and TUNEL reactive cells suggests that increased angiogenesis, decreased apoptosis and deregulated proliferation occur simultaneously during tumor progression in the oral mucosa. Presence of a mutant p53, increased bcl-2 expression and altered bax expression are also involved in this complex process.     

Antihyperlipidemic effect of Eugenia jambolana seed kernel on streptozotocin-induced diabetes in rats.

Abnormalities in lipid profile are one of the most common complications in diabetes mellitus, which is found in about 40% of diabetics. In the present study, anti-hyperlipidemic efficacy of Eugenia jambolana seed kernel (EJs-kernel) was evaluated in streptozotocin (STZ)-induced diabetic rats and the efficacy was compared with standard hypoglycemic drug, glibenclamide. The effect of oral administration of ethanolic extract of EJs-kernel (100 mg/kg body weight) was examined on the levels of cholesterol, phospholipids, triglycerides and free fatty acids in the plasma, liver and kidney tissues of STZ (55 mg/kg body weight)-induced diabetic rats. The plasma lipoproteins and tissues fatty acid composition were also monitored. STZ-induced diabetic rats, showed significant increase in the levels of cholesterol, phospholipids, triglycerides and free fatty acids which were considerably restored to near normal in EJs-kernel or glibenclamide treated animals. The plasma lipoproteins (HDL, LDL, VLDL-cholesterol) and fatty acid composition were altered in STZ-induced diabetic rats and these levels were also reverted back to near normalcy by EJs-kernel or glibenclamide treatment. It may be concluded that, EJs-kernel possesses hypolipidemic effect, which may be due to the presence of flavonoids, saponins, glycosides and triterpenoids in the extract. The hypolipidemic effect mediated by EJs-kernel may also be anticipated to have biological significance and provide a scientific rationale for the use of EJs-kernel as an anti-diabetic plant.     

Resistance of tumor interstitial pressure to the penetration of intraperitoneally delivered antibodies into metastatic ovarian tumors.

PURPOSE: Despite evidence that regional chemotherapy improves the treatment of metastatic peritoneal ovarian carcinoma, monoclonal antibodies have not shown significant success in i.p. delivery. The present study was designed to address the hypothesis that convective penetration of macromolecular antineoplastic agents depends on a positive pressure difference between the i.p. therapeutic solution and the tumor. EXPERIMENTAL DESIGN: Nude rats with human ovarian xenografts implanted in the abdominal wall were used in experiments to facilitate in vivo measurement of tumor pressure and the treatment of the tumor with i.p. solutions at high pressures. Penetration of (125)I-labeled trastuzumab was measured with quantitative autoradiography. RESULTS: Tumor pressure profiles showed peak pressures of 32 mm Hg with mean pressures (+/- SD, mm Hg) in 12 SKOV3 tumors of 9.7 +/- 8.3 and in 15 OVCAR3 tumors of 12.5 +/- 7.0. I.p. therapeutic dwells at 6 to 8 mm Hg (maximum feasible pressure) showed significantly less penetration of trastuzumab than in adjacent normal muscle. To establish a driving force for convection into the tumor, various maneuvers were attempted to reduce tumor pressure, including treatment with taxanes or prostaglandin E(1), elimination of tumor circulation, and removal of the tumor capsule. Tumor decapsulation decreased the pressure to zero but did not enhance the penetration of antibody. Binding to specific trastuzumab receptors on each tumor was shown to be not a significant barrier to antibody penetration. CONCLUSIONS: The results only partially support our hypothesis and imply that the microenvironment of the tumor is in itself a major barrier to delivery of charged macromolecules.     

CT-Cephalometry—A study in Indian population

Determination of obstructive site in obstructive sleep apnoea (OSA) is of paramount importance is planning the management. Cephalometric evaluation of lateral X-rays when combined with clinical assessment and fibreoptic examination of the airway helps in locating the site of obstruction. The usual technique of cephalometry has been modified so as to give a better delineation of the soft tissues. Holding a 2mm card board in the mouth and using barium paste helped in more accurate calculations. Using our technique, various parameters have been quantified and a number of controls were studied and normal range derived. Further improvement in cephalometry has been done by using C.T. cephlometry topogram technique. A topogram is a scan done on a running table top cranio-caudally. Using the topogram technique 38 OSA patients were evaluated for all the parameters. The technique, its advantages over traditional cephalometry and the values obtained in the study are discussed in this paper.     

Synthesis and Structure-Activity Relationships of Vasicine Analogues as Bronchodilatory Agents

The series of vasicine (1) analogues, an alkaloid from Adhatoda vasica Nees., were synthesized with changes in A, B or C rings. Compounds 13-19 were evaluated for in vitro bronchodilatory activity using isolated guinea pig tracheal chain. Compounds 3-8 were also synthesized in good yields using microwave-mediated synthesis under solvent free conditions. Compounds 5 and 8 with seven-member C ring were more active than etofylline and caused 100% relaxation of both the histamine and acetycholine pre-contracted guinea pig tracheal chain. The structure-activity relationship studies showed that the quinazoline and oxo functionalities were essential for activity. The compounds without C ring and instead having aliphatic and phenyl substitutions in B ring showed relaxation against histamine pre-contracted tracheal chain only, 2-methyl substituted analogues, 12 and 13, being most active with 100% relaxation effect.     

Statin-induced necrotizing autoimmune myopathy: a systematic review

Statins are a class of lipid-lowering medications used worldwide by millions of people and are safe for frequent use in most patients. However, they cause necrotizing autoimmune myopathy in some patients. We reviewed case reports of 80 patients from 2010 to present diagnosed with statin-induced necrotizing autoimmune myopathy (SINAM), aiming to analyze the clinical, physiological, serologic characteristics and outcomes of SINAM. The mean age of these patients was 66 ±9.4, the majority being male (61.3%). All patients reported proximal muscle weakness, and a few had myalgias, extra muscular symptoms such as dysphagia, and pulmonary complications. Most of the patients were on atorvastatin, simvastatin, or rosuvastatin. The mean creatine kinase was 10,094.2 ±7,351.7 U/l, and anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase enzyme was positive for 93.8% of patients. The majority of patients were started on steroids; other treatments were also used. Prompt cessation of statins and initiation of immunosuppressants reduced morbidity and mortality.     

Pure Sertoli cell tumor of the ovary: A case report

Pure Sertoli cell tumors are an uncommon variant of rare ovarian Sertoli‐Leydig cell tumors. Due to nonspecific clinical and imaging features, diagnosis is often made after histopathological examination. The prognosis is excellent as most are detected in the early stages and surgical resection is often curative in most cases.