The antitumor efficiency of combined electrochemotherapy and single dose irradiation on a breast cancer tumor model

Background

The aim of this study was to investigate the antitumor effectiveness of electrochemotherapy with cisplatin combined with suboptimal radiotherapy doses. Tumor radiosensitization was evaluated on large invasive ductal carcinoma tumors in Balb/C mice.

Materials and methods

Tumors of an average volume of 630 mm³ were treated with cisplatin, electric pulses, radiotherapy, electrochemotherapy, alone as well as in appropriate combinations. Tumors were irradiated with Cobalt-60 γ-rays at doses 3 Gy and 5 Gy in combination with electrochemotherapy using cisplatin. Controls included each of the treatments alone as well as the combination of the radiotherapy with electric pulses alone or with cisplatin alone. Antitumor effectiveness was evaluated by tumor growth delay, tumor-doubling time, inhibition ratio and the objective response rates.

Results

As anticipated, electrochemotherapy was more effective than the treatment with cisplatin alone or the application of the electric pulses alone. When treatments were combined with tumor irradiation at either 3 or 5 Gy, the combination with electrochemotherapy was more effective: at 5 Gy, 2 animals out of 8 were in complete remission 100 days later. In general the higher 5 Gy dose of γ-radiation was more effective than the lower one of 3 Gy.

Conclusions

The results of our study demonstrate that irradiation doses, 3 Gy or 5 Gy, increase the antitumor effectiveness of electrochemotherapy with cisplatin on invasive ductal carcinoma tumors. Good antitumor results were achieved in experimental tumors with a size comparable to clinical lesions, demonstrating that this three-modality combined treatment is useful for the treatment of large lesions even at sub-optimal radiotherapy doses.     

Increased frequency of α-synuclein in the substantia nigra in human immunodeficiency virus infection

The frequency of neurodegenerative markers among long surviving human immunodeficiency virus (HIV)-infected individuals is unknown, therefore, the present study investigated the frequency of α-synuclein, β-amyloid, and HIV-associated brain pathology in the brains of older HIV-infected individuals. We examined the substantia nigra of 73 clinically well-characterized HIV-infected individuals aged 50 to 76 years from the National NeuroAIDS Tissue Consortium. We also examined the frontal and temporal cortical regions of a subset of 36 individuals. Neuritic α-synuclein expression was found in 16% (12/73) of the substantia nigra of the HIV+cases and none of the older control cases (0/18). β-Amyloid deposits were prevalent and found in nearly all of the HIV+ cases (35/36). Despite these increases of degenerative pathology, HIV-associated brain pathology was present in only 10% of cases. Among older HIV+adults, HIV-associated brain pathology does not appear elevated; however, the frequency of both α-synuclein and β-amyloid is higher than that found in older healthy persons. The increased prevalence of α-synuclein and β-amyloid in the brains of older HIV-infected individuals may predict an increased risk of developing neurodegenerative disease.     

Functional brain imaging alterations in acne patients treated with isotretinoin

OBJECTIVE: Although there have been case reports suggesting a relationship between treatment with the acne medication isotretinoin and the development of depression and suicide, this topic remains controversial. In order for isotretinoin to cause depression, it must have an effect on the brain; however, the effects of isotretinoin on brain functioning in acne patients have not been established. The purpose of this study was to assess the effects of isotretinoin on brain functioning in acne patients. METHOD: Brain functioning in adults was measured with [(18)F]fluorodeoxyglucose positron emission tomography before and after 4 months of treatment with isotretinoin (N=13) or an antibiotic (N=15). RESULTS: Isotretinoin but not antibiotic treatment was associated with decreased brain metabolism in the orbitofrontal cortex (-21% change versus 2% change for antibiotic), a brain area known to mediate symptoms of depression. There were no differences in the severity of depressive symptoms between the isotretinoin and antibiotic treatment groups before or after treatment. CONCLUSIONS: This study suggests that isotretinoin treatment is associated with changes in brain functioning.     

A model for studying epithelial attachment and morphology at the interface between skin and percutaneous devices

Percutaneous devices are indispensable in modern medicine, yet complications from their use result in significant morbidity, mortality, and cost. Bacterial biofilm at the device exit site accounts for most infections in short-term devices. We hypothesize that advanced biomaterials can be developed that facilitate attachment of skin cells to percutaneous devices, forming a seal to preclude bacterial invasion. To study the skin/biomaterial interface systematically, we first identified biomaterials with physical properties compatible with histological processing of skin. Second, we developed an organ culture system to study skin response to implants. Organ cultures implanted with porous poly(2-hydroxyethyl methacrylate) [poly(HEMA)] or polytetrafluoroethylene (PTFE) could easily be evaluated histologically with preservation of the skin/biomaterial interface. Epithelial cells migrated down the cut edges of the biomaterial in a pattern seen in marsupialization of percutaneous devices in vivo. This in vitro model maintains skin viability and allows histologic evaluation of the skin/biomaterial interface, making this a useful, inexpensive test-bed for studies of epidermal attachment to modified biomaterials.     

Urinary 5-hydroxy indole acetic acid as a test for early diagnosis of acute appendicitis

OBJECTIVES: Acute appendicitis (AA) is the most common abdominal emergency. The appendix has abundant serotonin containing cells. Upon inflammation, serotonin is released in the blood and converted into 5-HIAA (5-hydroxy indole acetic acid). Measurement of the urine 5-HIAA (U-5-HIAA) could be a reliable marker of inflammation of the appendix. We have compared the powers of test performance of spot U-5-HIAA and spot U-5-HIAA/creatinin with other routine laboratory tests used for the diagnosis of acute appendicitis. DESIGN AND METHODS: Urine, serum, and blood samples of 110 patients who were admitted and observed in the emergency units of two university hospitals were studied. 5-HIAA was measured using HPLC, C-reactive protein by immunoturbidometry, WBC by electronic cell counting, and urine creatinine by the Jaffe method. Diagnostic accuracy of the various tests was evaluated by receiver operating characteristic (ROC) analysis. FINDINGS: The mean of spot U-5-HIAA in 39 patients with AA (nongangrenous) was 32 +/- 2.6 micromol/L, which was much higher than the mean of 40 non-appendicitis patients (NA) (5.5 +/- 0.6), 10 follicular hyperplasia (7.5 +/- 2.1), and 50 healthy control cases (4.1 +/- 0.5) with P < 0.001. The concentration of U-5-HIAA in 21 patients with gangrenous appendicitis (GA) (13.8 +/- 2.1) was also higher than NA patients and healthy individuals but lower than AA cases (P < 0.05). Considering 10 micromol/L as the cutoff point, this test shows 84% sensitivity and 88% specificity, with 90% and 81% positive and negative predictive values, respectively. The area under ROC curve (AUC) of U-5-HIAA in the diagnosis of AA (AUC = 0.903) was much larger than AUCs of U-5-HIAA/Cr (0.787), WBC (0.703), and CRP (0.660). CONCLUSION:: Urinary secretion of 5-HIAA increases significantly in acute appendicitis and measurement of spot U-5-HIAA gives higher diagnostic accuracy than other routine laboratory tests. While the inflammation progresses to necrosis of the appendix, the concentration of 5-HIAA decreases. This decrease could be a warning sign of perforation of the appendix.     

Synthesis and in vitro anti-Helicobacter pylori activity of 2-[(chlorobenzyl)thio]-5-(5-nitro-2-furyl)-1,3,4-thiadiazoles

A new series of 2-[(chlorobenzyl)thio]-5-(5-nitro-2-furyl)-1,3,4-thiadiazoles (6a–h) were synthesized and evaluated by the disc diffusion method against Helicobacter pylori. Four compounds which exhibited strong anti-H. pylori activity at concentration of 8–32 μg/disc (average of inhibition zone >20 mm) were further tested against 20 clinical isolates of H. pylori at lower concentrations. The averages of inhibition zone diameters indicated that all selected compounds exhibit better anti-H. pylori activity profile against clinical isolates of H. pylori with respect to standard drug metronidazole. Compound 6c, containing the 3-chlorobenzylthio moiety, was the most potent compound tested.