A change from gonadotropin releasing hormone antagonist to gonadotropin releasing hormone agonist therapy does not affect the oncological outcomes in hormone sensitive prostate cancer

Background

The aim of our retrospective study was to evaluate the 5-year survival and time to castration resistant prostate cancer in patients with hormone sensitive prostate cancer treated with the gonadotropin releasing hormone antagonist, degarelix. Another aim was to evaluate the effects of changing the treatment from degarelix to a gonadotropin releasing hormone agonist after achieving stable disease control, on the clinical and oncological outcomes.

Results

Our analysis was based on the data of 108 patients with prostate cancer who were treated with degarelix. Of these, the treatment was changed from degarelix to a gonadotropin releasing hormone agonist in 57 patients (changed group), and the treatment with degarelix was continued in the other 51 (continued group). The overall 5-year survival was statistically superior in the changed (96.6%) group than that in the continued (74.1%) group (p?=?0.006). The 5-year cancer-specific survival was also superior in the changed (100%) group than that in the continued (84.6%) group (p?=?0.027). The average time to castration resistant prostate cancer was comparable in both the changed (43.3 months) and continued (35.2 months) groups (p?=?0.117). Lower serum levels of prostate specific antigen and alkaline phosphatase were maintained after changing the therapy from degarelix to a gonadotropin releasing hormone agonist.

Conclusions

Degarelix is effective in the treatment of prostate cancer. Degarelix therapy can also be safely changed to a gonadotropin releasing hormone agonist without any adverse clinical or oncological effects.

     

Analysis of the positive feedback effect of estrogen on the release of gonadotropin in women

In order to elucidate the positive feedback mechanism of estrogen on gonadotropin release in women, the responses of plasma LH and FSH to the constant infusion of estradiol-17 beta for a prolonged period were studied. The infusion was initiated on various days of the follicular phase and maintained for 36-66 hr at a constant rate of 500 or 1,000 microgram/24 hr. When the stimulus of estradiol was sustained for more than 30 hr in the women of the middle or late follicular phase, a positive feedback effect to elicit gonadotropin surges was observed during the maintenance of the infusion. In contrast, the stimulus of estrogen was ineffective in the early follicular phase, even if sustained for a longer period up to 66 hr. Gonadotropin levels, also, increased after the end of infusion. The magnitude of the responses, however, was much smaller, as compared to spontaneous preovulatory gonadotropin surges. In all cases, the effect of estradiol was greater for LH than for FSH. It is suggested that: 1) Preovulatory gonadotropin surges are triggered by estrogen increments rather than the withdrawal of the negative feedback effect of estrogen. 2) Low levels of estrogen for a certain period of the early follicular phase may play an important role in priming the control system which responds to the positive feedback effect of estrogen.     

Role of Suspending and Recovery Media in the Survival of Frozen Shigella sonnei

Shigella sonnei was frozen at -20 C in saline, nutrient broth, and milk, and plated, after thawing, upon synthetic medium, nutrient agar, and blood heart infusion agar. There was a difference in the numbers of cells recovered when the frozen and thawed cells were grown on different media. The synthetic medium was unable to recover cells injured by freezing or did so only poorly compared to the complex media. The addition of meat extract, peptone, or Casamino acids to the synthetic medium improved its ability to recover injured cells as measured by bacterial colony counts. This is suggestive of metabolic injury caused by the freezing processes since the cells which survived freezing required an enriched medium for growth. In this paper the term metabolic injury is used to express a change in the nutritional requirements of the organisms which resulted in an increase in growth factor requirements. Freezing the cells in saline resulted in greater injury compared to cells frozen in nutrient broth or milk; this suggested that these suspending agents possessed some protective quality. The metabolic injury increased with an increase in the length of time the cells were held in the frozen state.     

Electron microscopic study of spermatogenesis in the lung fluke (Paragonimus miyazakii)

Summary The characteristics of spermatogenesis in a type of pulmonary parasite, Paragonimus miyazakii have been observed using the electron microscope. Groups of several spermatocytes revealed mutual cytoplasmic connection. That degree of this fusion increased as spermatogenesis progressed, and finally developed into a so-called cytophore. Then, this cytophore remained joined with a spermatid by a short stalk until the spermatid changed into a sperm. The nucleus of the spermatid became elongated with a string-like arrangement of the chromatin, which, in turn, showed increased electron density. At the pole of the spermatid, linearly arranged microtubules developed just below the plasma membrane. Close to an elongated portion at the pole, two separate flagella start growing and later fuse with the sperm itself. In the sperm tail a couple of tail filament complexes, longitudinally oriented slender mitochondria, and a tubular structure were present.     

Phylogenetic characterization of a new thermoacidophilic bacterium isolated from hot springs in Japan

Three strains of thermophilic-acidophilic bacteria isolated previously from different hot springs in Japan were characterized by molecular genetic methods. The strategy taken involved PCR amplification, sequencing and restriction pattern analysis of 16S rDNA, 16S-23S rDNA spacer polymorphism analysis and genomic DNA-DNA hybridization. A phylogenetic analysis based on 16S rDNA sequences showed that the new thermoacidophilic isolates formed a genetically coherent group at the species level and fell into a major cluster together with members of the genera Alicyclobacillus and Sulfobacillus with A. acidocaldarius and A. acidoterrestris as their closest relatives. The levels of binary sequence similarity between the isolates and the two Alicyclobacillus species were 97.6 to 97.9%, values considered low enough to warrant placement of the isolates in a distinct species of the genus Alicyclobacillus. The 16S rDNA restriction pattern analysis, but not 16S-23S rDNA spacer polymorphism analysis, was useful for differentiating the isolates from the established Alicyclobacillus species. DNA-DNA hybridization assays demonstrated a distinct phylogenetic position of our isolates as a genospecies within the genus Alicyclobacillus. On the basis of these results, the thermoacidophilic isolates should be classified into a new species of Alicyclobacillus. The results of this study suggest that this new genospecies of Alicyclobacillus is widely distributed in hot springs in Japan.     

Classification of amino acid spin systems using PFG HCC(CO)NH-TOCSY with constant-time aliphatic 13C frequency labeling

Summary We have developed a useful strategy for identifying amino acid spin systems and side-chain carbon resonance assignments in small ¹⁵N-, ¹³C-enriched proteins. Multidimensional constant-time pulsed field gradient (PFG) HCC(CO)NH-TOCSY experiments provide side-chain resonance frequency information and establish connectivities between sequential amino acid spin systems. In PFG HCC(CO)NH-TOCSY experiments recorded with a properly tuned constant-time period for frequency labeling of aliphatic ¹³C resonances, phases of cross peaks provide information that is useful for identifying spin system types. When combined with ¹³C chemical shift information, these patterns allow identification of the following spin system types: Gly, Ala, Thr, Val, Leu, Ile, Lys, Arg, Pro, long-type (i.e., Gln, Glu and Met), Ser, and AMX-type (i.e., Asp, Asn, Cys, His, Phe, Trp and Tyr).     

The influence of various plant hormones on the stimulatory action of red light on greening in excised etiolated cotyledons of cucumber

In etiolated cotyledons of cucumber (Cucumis sativus L. cv.Aonagajibai), preillumination with a short pulse of red lighteliminated the lag phase and stimulated Chl formation in thelinear phase during subsequent continuous illumination. Thistwofold effect was clearly distinguishable by varying the lengthsof the dark periods after preillumination. Pretreatment of excisedcotyledons with BA, GA₃ ethylene, or IAA stimulated Chl formationduring subsequent illumination. The effects of BA and GA₃ seemedindependent of both kinds of red light effects. However, ethyleneand IAA interacted with red light in increasing the rate ofChl formation during the linear phase. This may provide someclue to the red light action on Chl formation through its probablestimulation of ethylene production. (Received June 7, 1978; )