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S Tanda

Publications and source records attributed to S Tanda.

41 records · Page 3Linked to original sources

[A new drug delivery system in metastatic foci of cancer].

To improve the cancer chemotherapeutic effects on metastatic foci, we have developed a new drug delivery system based on two functional characteristics of the tumor vessels. Two functional characteristics of tumor vessel are summarized as follows: 1) A several-fold increase in tumor blood flow was brought about by angiotensin II-induced hypertension. The increase was selective and universal to the tumor vessels as long as the mean arterial blood pressure was kept under 150 mmHg. Such characterization was observed in micrometastatic foci. The concentration of anticancer drugs in tumor tissue could be increased by this function. Angiotensin-induced hypertension chemotherapy has been developed based on this characterization of tumor vessels. 2) Tumor blood flow almost decreased to zero when the mean arterial blood pressure was decreased to 60-65 mmHg by infusion of sodium nitroprusside. The stasis of tumor blood flow was also selective for the tumor tissues. The stasis suppressed a drug efflux from tumor tissues. By utilizing combination of these functional characteristics, we were able to enhance drug concentration X retention time in tumors remarkably. We named this drug delivery system "Flooding-the-castle chemotherapy". In these experiments, optimum blood pressures were kept under control by a computer system.

Angiotensin II↗

Retrovirus-like features and site specific insertions of a transposable element, tom, in Drosophila ananassae.

The tom element, putatively associated with optic morphology (Om) mutations in Drosophila ananassae, was identified as a retrovirus-like transposable element. The tom element was found to terminate with 475 (or 474) base pair direct repeats which are identical in sequence to each other. Southern blot and heteroduplex analyses showed the tom element to have high homology to 297 and 17.6, two retrotransposons found in D. melanogaster. As in the cases of 297 and 17.6, tom includes nucleotide sequences coding for a presumptive protease and reverse transcriptase, similar in amino acid sequence to those of the Moloney murine leukaemia virus. At the tom insertion site of the sn9g locus, a host DNA sequence (T)ATAT was found to be duplicated on each side of the tom insertion and all other tom elements examined were also flanked by (T)ATAT. In each of six cases, the 5' flanking host sequence was TATAT. These results indicate that the target sequence of the tom element may be TATAT and that the entire region or a part of this sequence was duplicated on insertion of the tom element.

Animals↗

Increased intratumor concentration of fluorescein-isothiocyanate-labeled neocarzinostatin in rats under angiotensin-induced hypertension.

On the basis of the observation that the tumor tissue blood flow selectively increases under angiotensin (AT)-induced hypertension, the change of the drug concentration in the tumor and normal tissues was examined in male Donryu rats. The intratumor concentration of fluorescein isothiocyanate-labeled neocarzinostatin was about 2-fold higher in the AT-induced hypertension group than in the control up to 20 min after the drug injection. In the normal organs or the uninvolved organs of the tumor-bearing rats, however, no clear increase was seen in the experimental group compared with the control, as anticipated from the observation of the tissue blood flow. The present study supports the hypothesis that the enhanced anticancer effect in chemotherapy under AT-induced hypertension formerly reported is due to the tumor-selective enhancement of the drug delivery.

Angiotensin II↗

[Intravital observations on the development of the tumor vascular system in rats].

By using transparent chambers in rats, it proved possible to observe directly the normal vascular pattern and early neovascular response to solid tumor growth at high magnification. Morphologic studies of the vascularization patterns were performed daily by construction of photomontages from color instant film taken with a Polaroid camera. Noteworthy results obtained in this study were: In the normal subcutaneous tissue within the chamber, the main vascular pattern was similar to that described by Nicoll and Webb, showing the so-called "arcuate arteriolar pattern". The thoroughfare channel reported by Chambers and Zweifach was also observed. The establishment of new functional capillaries was observed within 2 weeks following the implantation of AH109A and AH272 tumors. The sprouts of newly formed vessels were seen originating at the arterial ends of the host capillaries, where the blood velocity was relatively high. The formation of intricate networks in the tumor occurred easily in a haphazard way; the three modes of network formation observed were sprouting, cross-connection and splitting. Progressive dilatation and tortuosity were observed in the preexisting vessels, especially capillaries and venules, in the neighborhood of the tumor implant. The arterioles, however, remained little altered and in a location almost identical to that at the time of tumor implantation. The vascular systems in the tumors were proved to parallel those in the normal organs from which they originated, from the microfocus stage to the large tumor stage. An understanding of the differences in the vascular architecture between normal and tumor tissue seems to be essential in order to elucidate the mechanism of enhancement of therapeutic effect by angiotensin II induced hypertension chemotherapy.

Animals↗

Are entrenched characters developmentally constrained? Creating biramous limbs in an insect.

Are evolutionarily entrenched phenotypes highly constrained developmentally? We explored this question in the case of the uniramous appendages of fruit flies. We created bi- and polyramous antenna/leg combinations in four different genotypes. Each genotype consisted of two relevant mutations. We suggest that not all entrenched characters are strongly constrained by developmental processes and that there exists sufficient natural genetic variation to alter highly conserved phenotypes.

Animals↗