Pilot study of Panax quinquefolius (American ginseng) to improve cancer-related fatigue: a randomized, double-blind, dose-finding evaluation: NCCTG trial N03CA

Purpose

This pilot trial sought to investigate whether any of three doses of American ginseng (Panax quinquefolius) might help cancer-related fatigue. A secondary aim was to evaluate toxicity.

Methods

Eligible adults with cancer were randomized in a double-blind manner, to receive American ginseng in doses of 750, 1,000, or 2,000 mg/day or placebo given in twice daily dosing over 8 weeks. Outcome measures included the Brief Fatigue Inventory, vitality subscale of the Medical Outcome Scale Short Form-36 (SF-36), and the Global Impression of Benefit Scale at 4 and 8 weeks.

Results

Two hundred ninety patients were accrued to this trial. Nonsignificant trends for all outcomes were seen in favor of the 1,000- and 2,000-mg/day doses of American ginseng. Area under the curve analysis of activity interference from the Brief Fatigue Inventory was 460–467 in the placebo group and 750 mg/day group versus 480–551 in the 1,000- and 2,000-mg/day arms, respectively. Change from baseline in the vitality subscale of the SF-36 was 7.3–7.8 in the placebo and the 750-mg/day arm, versus 10.5–14.6 in the 1,000- and 2,000-mg/day arms. Over twice as many patients on ginseng perceived a benefit and were satisfied with treatment over those on placebo. There were no significant differences in any measured toxicities between any of the arms.

Conclusion

There appears to be some activity and tolerable toxicity at 1,000–2,000 mg/day doses of American ginseng with regard to cancer-related fatigue. Thus, further study of American ginseng is warranted.     

Acquired tracheoesophageal fistula following blunt trauma to the chest

Tracheoesophageal fistula following blunt chest trauma is rare. Typically the patient is a young male with an elastic chest wall who is involved in a motor vehicle accident. In this case the victim was a motorcyclist who collided with a stationary lorry. He underwent surgery 4 weeks after the injury made an uncomplicated recovery.     

Rapid detection of codon 460 mutations in the UL97 gene of ganciclovir-resistant cytomegalovirus clinical isolates by real-time PCR using molecular beacons

A rapid real-time polymerase chain reaction (PCR) assay using molecular beacons has been developed for the simultaneous detection of wild-type and mutant strains of cytomegaloviruses (CMV) with respect to codon 460 of the UL97 gene has been developed. The molecular beacons were designed to complement the wild-type codon 460 or the mutant sequence arising from a single base-pair difference (point mutation). Discrimination between wild-type and mutant templates was demonstrated as the beacons did not generate fluorescence with their respective mismatch targets but only with those that they were designed to perfectly anneal with. Samples that harbor mixed populations of CMV could also be readily recognized. Applied to a small number of clinical samples, the retrospective screening by this assay are in general concordance with that obtained by PCR-RFLP. Using molecular beacons strategy, codon 460 mutation was detected in ten out o the total number of 40 samples, whereas the latter method identified nine samples as containing the mutation. The discrepant result arose from the genotyping of one clinical sample as mixed (containing both wild-type and mutant CMV strains) by molecular beacons but as wild-type by PCR-RFLP, suggesting that this real-time strategy is possibly more sensitive for mutation analysis.     

Implementing the donor–acceptor approach in electronically conducting copolymers via electropolymerization

Electropolymerization has become a convenient method for synthesizing and characterizing complex organic copolymers having intrinsic electronic conductivity, including the donor (D)–acceptor (A) class of electronically conducting polymers (ECPs). This review begins with an introduction to the electrosynthesis of common second-generation ECPs. The information obtainable from electroanalytical studies, charge carriers such as polarons (positive and negative) and bipolarons (positive and negative) and doping will be discussed. The evolutionary chain of ECPs is then presented. ECPs comprising electron-rich D and electron-deficient A moieties have been shown to possess intrinsic electronic conductivity and unique optical and electronic properties. They are third generation ECPs and electropolymerization of mixtures of D and A leads to stoichiometrically controlled block copolymers. These D–A type ECPs are discussed on the basis of selected representative materials. Since the discovery of electropolymerization as a powerful tool to synthesize copolymers of conjugated monomers with a pre-determined ratio of D and A repeat units present in the polymer, the field of D–A type ECPs has grown considerably and the literature available since 2004 to 2021 is summarized and tabulated. Electronic and optical properties of the materials determined by computational chemistry are presented. The data obtained from electrochemical and optical methods are compared with those obtained from computational methods and reasons for discrepancies are given. The literature on the concept of electropolymerization extended to synthesizing triblock and many-block copolymers is reviewed. Finally, applications of D–A polymers in optoelectronic devices (organic solar cells and field-effect transistors) and in bio-imaging are explained quoting appropriate examples.

Electropolymerization has become a convenient method for synthesizing and characterizing complex organic copolymers having intrinsic electronic conductivity, including the donor (D)–acceptor (A) class of electronically conducting polymers (ECPs).     

Further data supporting that paclitaxel-associated acute pain syndrome is associated with development of peripheral neuropathy: North Central Cancer Treatment Group trial N08C1

BACKGROUND:

Paclitaxel causes an acute pain syndrome (P‐APS), occurring within days after each dose and usually abating within days. Paclitaxel also causes a more classic peripheral neuropathy, which steadily increases in severity with increasing paclitaxel total doses. Little detail is available regarding the natural history of these 2 syndromes, or any relationship between them, although a recent publication does provide natural history data about weekly paclitaxel, supporting an association between the severity of P‐APS and eventual peripheral neuropathy symptoms.

METHODS:

Patients entering this study were about to receive paclitaxel and carboplatin every 3 weeks. Daily questionnaires were completed for the first week after every chemotherapy dose, and European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire, Chemotherapy‐Induced Peripheral Neuropathy 20‐item instruments were completed weekly.

RESULTS:

The P‐APS severity peaked on day 4 after the initial chemotherapy dose, with 12%, 29%, 23%, and 36% of patients having maximal pain scores of 0, 1 to 4, 5 or 6, or 7 to 10 during the first week after the first dose of therapy, respectively. Patients with P‐APS scores of 0 to 4 with the first dose of chemotherapy had less eventual sensory neuropathy than did patients with P‐APS scores of 5 to 10 (P = 0.001). With regard to the more peripheral neuropathy, sensory neuropathy was more problematic than was either motor or autonomic neuropathy. Numbness and tingling were more common components of the sensory neuropathy than was pain.

CONCLUSIONS:

Patients with worse P‐APS severities appear to have more eventual chemotherapy‐induced peripheral neuropathy. This provides support for the concept that P‐APS is a form of nerve pathology. Cancer 2012. © 2012 American Cancer Society.     

Antagonism of endogenous growth hormone-releasing hormone (GHRH) leads to reduced proliferation and apoptosis in MDA231 breast cancer cells

GHRH, in addition to stimulating the release of growth hormone (GH) from the pituitary, is a trophic factor for pituitary somatotrophs. Growth hormone-releasing hormone is also expressed in the gonads, gastrointestinal tract, pancreas, thymus, and lymphocytes, as well as in tumors of the pancreas, lung, central nervous system, and breast. Since GHRH has mitogenic effects, we examined the hypothesis that GHRH is an autocrine/paracrine growth factor in neoplastic breast tissue. The effect of disrupting endogenous GHRH on cell growth and apoptosis of MDA231 cells was examined through the use of a competitive GHRH antagonist, [N-acetyl-Tyr1, D-Arg2] fragment 1–29Amide (GHRHa). Cell proliferation was determined by direct cell counting and tritiated thymidine incorporation. Apoptosis was analyzed by examination of DNA laddering and nuclear condensation. GHRHa resulted in a dose-dependent, transient, and reversible decrease in cell number, proliferation rate, and tritiated thymidine uptake. Conversely, GHRHa led to a marked and dose-dependent increase in both DNA laddering and nuclear condensation. These results indicate that disruption of endogenous GHRH action in MDA231 cells results in both decreased cellular proliferation and increased apoptosis. Taken together, the findings suggest that endogenous GHRH acts as an autocrine/paracrine factor in the regulation of growth of at least some breast cancer cell types.