Muscle structural changes during typical mountaineering expeditions to the Himalayas were assessed by taking muscle biopsies from 14 mountaineers before and after their sojourn at high altitude (greater than 5000 m for over 8 weeks). M. vastus lateralis samples were analyzed morphometrically from electron micrographs. A significant reduction (-10%) of muscle cross-sectional area was found on CT scans of the thigh. Morphologically this loss in muscle mass appeared as a decrease in muscle fiber size mainly due to a loss of myofibrillar proteins. A loss of muscle oxidative capacity was also evident, as indicated by a decrease in the volume of muscle mitochondria (-25%). In contrast, the capillary network was mostly spared from catabolism. It is therefore concluded that oxygen availability to muscle mitochondria after prolonged high-altitude exposure in humans is improved due to an unchanged capillary network, supplying a reduced muscle oxidative capacity.

This paper describes the synthesis of alpha-aminoisobutyric acid-11C (11C-AIB) and studies its body distribution in healthy and tumor-bearing animals. High tissue levels of 11C-AIB were found in organs with high metabolic activity (pancreas, liver, kidney). The prostate tumor 11C-AIB concentrations are significantly lower than that of pancreas, liver, and kidney, but increased when compared with normal prostate levels. Effective chemotherapy, which reduces tumor growth of two different prostate adenocarcinoma cell lines (R-3327-H, R-3327-G) also decreases 11C-AIB levels and the 11C-AIB prostate to tumor ratio.

Inhibitors of polyamine synthesis were tested for therapeutic effectiveness on transplantable prostate cancer. Inhibition of either ornithine decarboxylase or S-adenosyl-L-methionine decarboxylase (AMDC) by α-difluormethylornithine (DFMO) or methylglyoxal-bis[guanylhydrazone] (MGBG), respectively, was associated with significant antitumor effect. The combination of DFMO with MGBG was not only more effective but no more toxic than MGBG alone. Combination of MGBG with 9-B-D-arabinofuranosyladenine, an indirect effector of SAMDC, failed to increase therapeutic effectiveness of MGBG.

No abstract

alpha-Difluoromethylornithine (DFMO) and methylglyoxal-bis-guanylhydrazone (MGBG), when administered simultaneously, inhibited growth and were highly toxic to the Dunning R 3327-G hormone-resistant prostatic adenocarcinoma transplanted into Copenhagen rats. Neither DFMO (2%) nor MGBG at a nontoxic dose (15 mg/kg) inhibited tumor growth, but total (47% early cure rate) or near total suppression of growth of established tumors was observed in rats receiving both treatments.

The polyamines, putrescine, spermidine, and spermine, are fundamentally related to both normal and neoplastic cell proliferation. The prostate gland and prostatic tumors in man and rodents contain large amounts of polyamines. This suggests that inhibition of polyamine biosynthetic enzymes, ornithine decarboxylase (ODC) and S‐adenosyl‐methionine decarboxylase (SAMDC) may retard the growth of prostatic cancer. Since alpha‐difluoromethylornithine (DFMO) and methylglyoxal‐bis‐guanylhydrazone (MGBG) are irreversible and competitive inhibitors of ODC and SAMDC, respectively, they were tested as single agents and in combination on a transplantable rapidly growing and hormone‐resistant G subline of the Dunning R‐3327 rat prostatic adenocarcinoma. Groups of rats bearing tumors were treated with various regimens of DFMO, MGBG, and DFMO plus MGBG, daily for 21 days. Analysis of differences in tumor growth between treatment groups and controls showed DFMO had no antitumor effect but was well tolerated, MGBG retarded growth rate significantly but resulted in drug deaths in over 50% of the animals, and the combination of DFMO and MGBG resulted in rapid decline in tumor growth rates after 5 to 9 days of treatment with reduced toxicity. At 21 days, or death, 38 of 60 (63%) rats had no viable tumor on histologic study, whereas tumor was present in each of the animals in the other groups. Alpha‐difluoromethylornithine increased the intracellular uptake of MGBG and potentiated the antigrowth activity of MGBG on a hormone refractory rat prostatic tumor with less toxicity than MGBG alone. Cancer 53:1294‐1298, 1984.

This study was undertaken to determine whether hormonal stimulation followed by chemotherapy with a cell-cycle specific agent would improve the effectiveness of the chemotherapy in a prostatic adenocarcinoma model. One hundred Copenhagen rats were randomised into 5 equal groups and injected subcutaneously with 2 x 10(7) cells of Dunning G strain prostatic adenocarcinoma. The groups were treated in the following fashion: 1. sham operated controls, 2. castration, 3. castration and methotrexate, 4. castration, testosterone and methotrexate and 5. castration and testosterone. When the tumours became palpable, all animals received the surgery to which they were randomised. Subsequent hormonal and chemotherapy was started 1 week thereafter. Therapy was given for 5 consecutive days followed by a 16-day recovery period and then continued in a cyclical fashion. Serial measurements of animal weights and tumour size were obtained. Analysis of tumour growth was restricted to the first 29 days of therapy because of a rapid decline in animal survival beyond that point. The group treated with castration, testosterone, and methotrexate inhibited tumour growth more than any other group and was the only group that was significantly different from control (P less than 0.05).

Administration of the nephrotoxic agent, bichloride of mercury (HgCl2), to BALB/c mice bearing subcapsular renal tumor transplants induced early preferential necrosis of the tumor cells compared with mercury‐treated normal kidney tubular cells and untreated control tumors. The principle is established that a selective proximal tubular poison is also toxic for a tumor of the same cellular origin.