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Prasad S Adusumilli

Publications and source records attributed to Prasad S Adusumilli.

34 records · Page 2Linked to original sources
PubMed2004

Angiogenesis inhibition by an oncolytic herpes virus expressing interleukin 12.

PURPOSE: Oncolytic herpes simplex viruses (HSVs) may have significant antitumor effects resulting from the direct lysis of cancer cells. HSVs may also be used to express inserted transgenes to exploit additional therapeutic strategies. The ability of an interleukin (IL)-12-expressing HSV to treat squamous cell carcinoma (SCC) by inhibition of tumor angiogenesis is investigated in this study. EXPERIMENTAL DESIGN: A replication-competent, attenuated, oncolytic HSV carrying the murine IL-12 gene (NV1042), its non-cytokine-carrying analog (NV1023), or saline was used to treat established murine SCC flank tumors by intratumoral injection. The expression of secondary antiangiogenic mediators was measured. Angiogenesis inhibition was assessed by in vivo Matrigel plug assays, flank tumor subdermal vascularity, and in vitro endothelial cell tubule formation assay. RESULTS: Intratumoral injections of NV1042 (2 x 10(7) plaque-forming units) into murine SCC VII flank tumors resulted in smaller tumor volumes as compared with NV1023 or saline. IL-12 and IFN-gamma expression in tumors was 440 and 2.2 pg/mg, respectively, at 24 h after NV1042 injection, but both IL-12 and IFN-gamma were undetectable (<0.2 pg/mg) after NV1023 or saline injections. Expression of two antiangiogenesis mediators, monokine induced by IFN-gamma and IFN-inducible protein 10, was elevated after NV1042 treatment. Matrigel plug assays of NV1042-transfected SCC VII tumor cells demonstrated significantly decreased hemoglobin content and microvessel density as compared with NV1023 and PBS. Excised murine flank tumors treated with NV1042 had decreased subdermal vascularity as compared with NV1023 and PBS. Both splenocytes and IL-12 expression by NV1042 were required for in vitro inhibition of endothelial tubule formation. CONCLUSIONS: IL-12 expression by an oncolytic herpes virus enhances therapy of SCC through antiangiogenic mechanisms. Strategies combining HSV oncolysis with angiogenesis inhibition merit further investigation for potential clinical application.

Animals↗
PubMed2004

Infection with oncolytic herpes simplex virus-1 induces apoptosis in neighboring human cancer cells: a potential target to increase anticancer activity.

PURPOSE: The antitumor efficacy of a herpes simplex virus (HSV)-1 oncolytic virus depends on the cytotoxic effect of the virus, but also on viral replication and spread within the tumor. Apoptosis is considered a defense mechanism of infected cells that minimizes the spread of viral progeny by limiting cellular production of virus. We sought to determine whether oncolytic HSV-1 infection induces apoptosis in neighboring, uninfected cells and whether manipulation of apoptosis can increase viral replication and cytotoxicity. EXPERIMENTAL DESIGN: NV1066 is an oncolytic HSV-1 mutant that contains the marker gene for enhanced green fluorescent protein. OCUM human gastric cancer cells were infected with NV1066 in vitro and inspected for apoptosis by Hoechst and terminal deoxynucleotidyltransferase-mediated nick end labeling staining and for infection by expression of green fluorescence. RESULTS: A significant increase in apoptosis was seen in cells infected by NV1066. More interestingly, a significant percentage (10%) of uninfected cells also proceeded to apoptosis. After NV1066 infection, cells were also treated with N-acetylcysteine (NAC), an inhibitor of apoptosis. By day 4 after infection, 2.7x more NV1066 was produced in cells exposed to NAC than in those not exposed to NV1066 (P = 0.04). NAC also increased tumor kill when administered with virus. CONCLUSIONS: These data suggest that NV1066 induces apoptosis in uninfected cocultured cells, potentially hindering propagation of viral progeny and concomitant tumor kill. Inhibition of apoptosis may improve the efficacy of oncolytic HSV-1 therapy.

Acetylcysteine↗
PubMed2004

The prevalence and predictors of herbal medicine use in surgical patients.

BACKGROUND: Despite the rapid rise in herbal medicine consumption, explicitly eliciting and documenting herbal medicine usage among surgical patients is poor. STUDY DESIGN: A survey by means of a self-administered questionnaire was conducted among patients undergoing elective surgery inquiring into the self-health perceptions, herbal medicine use, and communication of such usage to surgical health-care staff. RESULTS: Sixty-five percent (n =2,186) of all the patients undergoing elective surgery completed the survey during a 10-week period. Fifty-seven percent of respondents admitted to using herbal medicine at some point in their life, 38% in the past 2 years (eg, echinacea [48%], aloe vera [30%], ginseng [28%], garlic [27%], and ginkgo biloba [22%] were the most common). One in six respondents continued the use of herbal medicine during the month of surgery. Herbal medicine usage was significantly higher among patients undergoing a gynecologic procedure (odds ratio [OR] 1.68; 95% confidence interval [CI] 1.29 to 2.18) and patients with a self-perception of good health (OR 1.32; 95% CI 1.04 to 1.69); it was lower among patients with a history of pulmonary symptoms (OR 0.77; 95% CI 0.62 to 0.94), African Americans (OR 0.69; 95% CI 0.51 to 0.95), in patients having a primary care physician (OR 0.71; 95% CI 0.52 to 0.98), in patients with a history of diabetes mellitus (OR 0.46; 95% CI 0.32 to 0.68), and in patients undergoing vascular surgery (OR 0.19; 95% CI 0.07 to 0.48). CONCLUSIONS: Herbal medicine use is common among surgical patients and is consistent with the substantial increase in the use of alternative medical therapies. Awareness of this rising herbal medicine usage and documentation of the use of herbal medicines by surgical health-care staff is important to prevent, recognize, and treat potential problems that may arise from herbal medications taken alone or in conjunction with conventional medications during the perioperative period.

Adult↗
PubMed2003

The replication-competent oncolytic herpes simplex mutant virus NV1066 is effective in the treatment of esophageal cancer.

BACKGROUND: The oncolytic herpes simplex-1 virus, NV1066, is a replication-competent virus that has been engineered to infect and lyse tumor cells selectively and to carry a transgene for enhanced green fluorescent protein (EGFP). The purpose of this study was to determine viral cytotoxicity in an esophageal cancer cell line and to determine whether EGFP expression could be used as a marker of viral infection. METHODS: BE3 esophageal adenocarcinoma cells were infected with NV1066 in vitro to determine cell kill and viral replication. EGFP expression was assessed by flow cytometry. The in vivo anti-tumor activity of NV1066 was tested in subcutaneous and intraperitoneal xenograft models. EGFP expression was localized in vivo by fluorescent microscopy and fluorescent laparoscopy. RESULTS: NV1066 effectively replicated within and killed BE3 cells in vitro and in vivo. EGFP expression identified infected tumor cells. After NV1066 treatment in vivo, EGFP expression localized to the tumor. In an intraperitoneal tumor model, EGFP could be visualized endoscopically using a laparoscope with a fluorescent filter. CONCLUSIONS: NV1066 has oncolytic activity against the BE3 cell line and may be a useful therapy against esophageal cancer. EGFP expression localizes the virus and may help to identify tumor deposits in vivo. Oncolytic activity with NV1066 against gastrointestinal cancers may potentially be tracked by endoscopy.

Adenocarcinoma↗
PubMed2002

Hemoperitoneum from spontaneous rupture of a liver cell adenoma in a male with hyperthyroidism.

Spontaneous liver rupture is uncommon, is difficult to diagnose, and carries a high mortality. Liver cell adenoma is a rare benign liver tumor with increasing incidence in women on oral contraceptive pills, and they have been reported to rupture spontaneously. In men such a phenomenon is an extreme rarity. In animal experiments thyroid hormone is proven to play a role in the growth of liver cell-derived neoplasms as they do in normal hepatocyte proliferation. An association of liver cell adenoma and hyperthyroidism in humans has not been previously reported. We present the successful management of an unusual case of spontaneous hemoperitoneum from rupture of a liver cell adenoma in a young man with hyperthyroidism.

Adenoma, Liver Cell↗
PubMedDate not supplied

Use of positron emission tomography to target prostate cancer gene therapy by oncolytic herpes simplex virus.

Herpes simplex virus (HSV) oncolytic gene therapy is a promising treatment modality against cancer. We have demonstrated that androgen-induced cellular changes enhance oncolytic viral replication and improve efficacy in the treatment of androgen-dependent prostate cancer cell line. Imaging of changes in 2-deoxy-2-[F-18]fluoro-D-glucose (FDG) uptake by positron emission tomography (PET) is a sensitive method of detecting altered cellular metabolism involved in cancer therapy. We therefore hypothesized that FDG-PET can predict tumor response to oncolytic HSV therapy. In this study, androgen increased cell kill (74%) in vitro and enhanced viral yield (2.4-fold) in vivo following HSV therapy. This enhanced efficacy was predicted by high FDG accumulation in intact animals compared to low FDG uptake following orchiectomy (p = 0.002). This proof-of-concept study provides the mechanistic basis for selecting patients for targeted oncolytic viral therapy by means of a noninvasive molecular imaging method in the treatment of prostate cancer.

Animals↗
PubMedDate not supplied

Left-handed surgeons: are they left out?

BACKGROUND: Left-handedness has been considered a simple inconvenience by some or something as convoluted as "the sinister," the Latin word for the left, by others. One in ten medical personnel is left-handed. The perceptions of left-handed surgeons regarding their laterality related inconveniences are unknown. OBJECTIVES: To determine the perceptions of left-handed surgeons and the way it has affected their surgical training and career. DESIGN AND SETTING: Web-based survey of left-handed surgeons. PARTICIPANTS: Left-handed surgeons in 2 boroughs of New York City, Manhattan and Brooklyn. METHODS: Distribution and completion of the survey. MAIN OUTCOME MEASURE: Career-oriented concerns of left-handed surgeons. RESULTS: Three percent of left-handed surgeons received laterality related mentoring during medical school. Ten percent of the programs mentored left-handed surgical residents, and 13% of the programs provided left-handed instruments during surgical residency. Laparoscopy and laparoscopic instruments did not eliminate the problems associated with instrument handling to left-handed surgeons. Ten percent of the left-handed surgeons expressed concerns when asked whether they would be comfortable being treated by another left-handed surgeon when they are the patients themselves. CONCLUSIONS: This study reveals the perceptions of left-handed surgeons in adapting to a right-handed world. Early laterality related mentoring in medical school and during surgical residency with provision of left-handed instruments might reduce the inconveniences of left-handed surgeons learning.

Attitude of Health Personnel↗