Oncolytic herpes viral therapy is effective in the treatment of hepatocellular carcinoma cell lines

The rising incidence of hepatocellular carcinoma (HCC) in western countries, along with the poor prognosis offered by present-day treatment modalities, makes novel therapies for this disease necessary. Oncolytic herpes simplex viruses (HSV) are replication-competent viruses that are highly effective in the treatment of a wide variety of experimental models of human malignancies. This study seeks to investigate the effectiveness of oncolytic herpes viruses in the treatment of primary HCC cell lines. Sixteen commercially available human HCC cell lines were studied. G207 is an attenuated, replication-competent, oncolytic HSV engineered to selectively replicate within cancer cells. Cell lines were tested for viral sensitivity to G207 and their ability to support viral replication using standard cytotoxicity and viral replication assays. Eleven of 16 cell lines were moderately to highly sensitive to G207 viral oncolysis. HCC cell lines additionally demonstrated the ability to support viral replication in vitro with as high as 800-fold amplification of the administered viral dose observed. G207 is cytotoxic to, and efficiently replicates within, HCC cell lines in vitro. From these data, we suggest that oncolytic HSV therapy may have a role in the treatment of HCC, and in vivo studies are warranted. Presented in part at the 2005 American Hepato-Pancreato-Biliary Association Congress, Hollywood, Florida, April 14–17, 2005. Supported by grants R01CA75461 and R01CA72632 from the National Institutes of Health, and by grant MBC-99366 from the American Cancer Society (Yuman Fong).     

Distraction Osteogenesis of Ankylosed Front Teeth with Subsequent Orthodontic Fine Adjustment

OBJECTIVE: Conventional therapeutic approaches to correct ankylosed anterior teeth in infraposition require compromises involving esthetics and function. The combined approach of distraction and early orthodontic fine adjustment, not yet established as a routine, promises better results concerning the bone conditions and gingival development. CASE HISTORIES: Both female patients had suffered a trauma to the front teeth during early mixed dentition resulting in ankylosed central incisors in infraposition. At the ages of 14 years and 2 months and 15 years and 2 months, respectively, we carried out segment distraction by means of a bone-supported internal distractor followed by orthodontic fine adjustment after having shortened the consolidation phase. Both ankylosed front teeth could be successfully aligned, leading to an increase in bone and harmonization of the gingival margin in the dental arch. At ten and 14 months after the conclusion of treatment, we observed only few deviations in the dental situation compared to posttherapeutic findings. CONCLUSION: From a functional and esthetic point of view, therapy involving combined orthodontics and surgery is superior to conventional therapy. Orthodontic fine adjustment should be considered as a continuation of the distraction procedure.     

Comparative assesment of gingival thickness using transgingival probing and ultrasonographic method.

A decided attitude of expectation among many patients has given a new perspective to regenerative and plastic periodonta surgery. With authors emphasizing on the importance of gingival thickness, attempts are being made to obtain necessary information atraumatically and rapidly. Hence in the present study an attempt has been made to compare the two methods of assessing gingival thickness i.e transgingival probing and ultrasonographic method and also assess the gingival thickness in relation to central incisor lateral incisor and canine in Indian population. The gingival thickness was assessed in patients with healthy gingiva by both the methods. It was observed that transgingival probing method significantly over estimated the thickness of gingiva than the ultrasonographic method and the thickness of gingiva varies with morphology of the crown. It was concluded that compared to transgingival probing ultrasonographic method assesses gingiva thickness more accurately, rapidly and atraumatically.     

Phospho-akt expression is associated with a favorable outcome in non-small cell lung cancer.

Akt, a Serine/Threonine protein kinase, mediates growth factor-associated cell survival. Constitutive activation of Akt (phosphorylated Akt, P-Akt) has been observed in several human cancers, including lung cancer and may be associated with poor prognosis and chemotherapy and radiotherapy resistance. The clinical relevance of P-Akt in non-small cell lung cancer (NSCLC) is not well described. In the present study, we examined 82 surgically resected snap-frozen and paraffin-embedded stage I to IIIA NSCLC samples for P-Akt and Akt by Western blotting and for P-Akt by immunohistochemistry. P-Akt protein levels above the median, measured using reproducible semiquantitative band densitometry, correlated with a favorable outcome (P = 0.007). Multivariate analysis identified P-Akt as a significant independent favorable prognostic factor (P = 0.004). Although associated with a favorable prognosis, high P-Akt levels correlated with high tumor grade (P = 0.02). Adenocarcinomas were associated with low P-Akt levels (P = 0.039). Akt was not associated with either outcome or clinicopathologic variables.Cytoplasmic (CP-Akt) and nuclear (NP-Akt) P-Akt tumor cell staining was detected in 96% and 42% of cases, respectively. Both CP-Akt and NP-Akt correlated with well-differentiated tumors (P = 0.008 and 0.017, respectively). NP-Akt also correlated with nodal metastases (P = 0.022) and squamous histology (P = 0.037).These results suggest P-Akt expression is a favorable prognostic factor in NSCLC. Immunolocalization of P-Akt, however, may be relevant as NP-Akt was associated with nodal metastases, a known poor prognostic feature in this disease. P-Akt may be a potential novel therapeutic target for the management of NSCLC.     

Dehiscent temporomandibular joint

The appearance of an acute effusion in a well-pneumatized temporal bone directs attention to the nasopharynx and skull base. Two patients are described in whom dehiscence of the temporomandibular joint allowed herniation of the contents of the joint posteromedically, where they obstructed the middle ear entrance of the eustachian tube, the protympanum. This is, to the authors' knowledge, a previously unreported cause of an acute middle ear and mastoid effusion.     

Deep venous thrombosis in the surgical intensive care unit

The ICU patient population is at a high risk for the development of deep venous thrombosis leading to a potentially fatal pulmonary embolism. It is vital to appreciate this risk and apply appropriate prophylaxis. Constant vigilance is required, as deep venous thrombosis and pulmonary emboli can develop and progress despite standard prophylactic measures. In unstable patients, more aggressive prophylaxis may be warranted, including the use of inferior vena cava filters. A high index of suspicion and a low threshold for screening and diagnostic testing will allow earlier recognition and treatment of this lifethreatening condition. Treatment decisions are based on clinical suspicion, diagnostic examination results, and the potential complications of difficult treatment modalities.     

Olfactory bulb DA receptors may be located on terminals of the olfactory nerve.

The glomerular layer of the olfactory bulb contains a substantial population of dopaminergic neurons. We determined the quantity and location of D1 and D2 dopamine receptors which are the presumed targets of these neurons. Binding of the D1 selective ligand [3H]SCH23390 was slightly above background and was distributed through all layers of the bulb except the olfactory nerve layer. In contrast there were relatively high levels of [3H]spiperone binding to D2 DA receptors in the glomerular and olfactory nerve layers. The presence of relatively high concentrations of D2 DA receptors in both the nerve layer and glomerular layer suggests the novel hypothesis that these receptors may be localized on terminals of the olfactory nerve.     

Thyroid stimulating hormone response to thyrotropin in prepubertal depression

In an effort to evaluate whether differences exist in the hypothalamic-pituitary-thyroid axis of depressed children, a thyrotropin releasing hormone (TRH) stimulation test was administered to 55 prepubertal subjects who were divided into three groups matched for age and sex: a depressed group (endogenous N = 15, nonendogenous N = 15), a psychiatric nondepressed control group (N = 16), and a normal control group (N = 9). Each subject was tested at two dosages of TRH, 2 micrograms/kg and 7 micrograms/kg. Increasing age and female sex were positively correlated with a greater thyroid stimulating hormone (TSH) response. TSH response to TRH was examined with subjects reclassified by severe suicidal ideation, severe aggression, and parental history of alcoholism. Results of this study are contrasted with the adult psychiatric literature.     

Tachykinin receptor cross-talk. Immunological cross-reactivity between the external domains of the substance K and substance P receptors.

In the present study, we have chemically synthesized peptides which correspond to the four putative extracellular domains of the predicted substance K (SK) receptor protein and raised specific polyclonal antibodies against these peptides. These antibodies were then tested for both structural and functional recognition of epitopes on the substance P (SP) receptor on rat AR42J pancreatic cells and human IM9 lymphoblasts, which express the SP receptor, but not the SK receptor. Antibodies directed against the first, second, and fourth external domains of the predicted SK receptor recognized a 58-kDa protein on AR42J cells. This protein has a molecular weight similar to the previously demonstrated SP receptor on both AR42J cells and IM9 cells. Furthermore, antibodies against the second and fourth extracellular domains significantly inhibited specific 125I-SP binding on both AR42J and IM9 cells, and also significantly inhibited SP-induced mobilization of [Ca2+]i on AR42J cells. These data suggest that the second and fourth extracellular domains of the SK and SP receptors may share common structural motifs for ligand binding and signaling mechanism.