Long-term survival in low-grade endometrial stromal sarcoma with childbirth and multidisciplinary treatment: a case report.

INTRODUCTION: Low-grade endometrial stromal sarcoma is very rare and difficult to diagnose in the early stage. A standard treatment has not been established. In this case report of a patient with long-term survival, we describe an effective treatment for advanced low-grade endometrial stromal sarcoma. CASE PRESENTATION: A 24-year-old Japanese woman who presented with prolonged menstruation was diagnosed with leiomyoma on the basis of a specimen resected transvaginally. She underwent ten resections in 10 years without a malignancy diagnosis. During this period, she gave birth. At age 34 years, she visited our hospital, complaining of lower abdominal pain. A 10cm tumor was detected behind her uterus. The disease was diagnosed as an advanced malignant ovarian tumor before surgery. A laparotomy was performed, with many remnants left in the abdominal cavity. The final diagnosis was advanced low-grade endometrial stromal sarcoma. After 12 cycles of gemcitabine and docetaxel combination chemotherapy, the tumor disappeared completely. A retrospective pathological review of the specimens resected transvaginally showed that the tumors included low-grade endometrial stromal sarcoma elements. When the patient was age 42 years, the sarcoma recurred. It was detected around the right diaphragm and liver. Despite administration of gemcitabine and docetaxel, ascites and pleural effusion accumulated. Administration of medroxyprogesterone acetate, leuprorelin acetate, and anastrozole gradually reduced the ascites and pleural effusion. In addition to the three hormone drugs, 18 cycles of paclitaxel and carboplatin were administered. The patient recovered from her critically ill state and is currently alive with reduced tumor at age 45 years. CONCLUSIONS: Our patient with low-grade endometrial stromal sarcoma whose disease began in her youth gave birth and experienced long-term survival with surgery, chemotherapy, and hormone therapy.

Metal ion binding of modified pyrimidine-base pairs in DNA duplexes.

We report the synthesis and metal ion-binding properties of DNA duplexes containing 5-substituted uracil ((X)U) pairs, such as 5-bromouracil, 5-fluorouracil and 5-cyanouracil pairs. Thermal denaturation studies of these modified DNA duplexes revealed that the DNA duplexes were stabilized in the presence of Hg(II) ions in acidic and neutral solutions. On the other hand, the duplexes were stabilized in the presence of Hg(II) and Ag(I) ions. These results indicated that (X)U-Hg(II)-(X)U complex was formed in the acidic and neutral solutions, then, in the basic solutions (X)U-Ag(I)-(X)U complex as well as the (X)U-Hg(II)-(X)U complex were formed. ESI-TOF MS analysis also indicated formation of the metal ion-DNA complexes.

Preparation and metal ion-binding of 4-N-substituted cytosine pairs in DNA duplexes.

We report the synthesis and metal ion-binding properties of DNA duplexes containing 4-N-substituted cytosine base pairs. Thermal denaturation studies of these modified DNA duplexes in the presence of various metal ions revealed that the DNA duplexes containing 4-N-carboxymethylcytosine (1) base pair(s) bound Ag (I), Ni(II), and Cu(II) ions. Moreover, ESI-TOF MS analysis of the DNA duplexes containing 1-1 base pair(s) in the presence of Cu(II) ions was consistent with one 1-1 base pair region binding one equivalent of Cu(II) ions. These results indicate that the DNA duplexes containing 1-1 base pair(s) may be useful as a new metal ion-binding motif.

Preparation of diverse metal binding sites along the helical structure of duplex DNA.

DNA duplexes containing 4-N-carboxymethylcytosine (1) were synthesized: duplex-I (5'-GTGACCA1TGCAG TG-3':3'-CACTGGT1ACGTCAC-5'), duplex-II (5'-GC CCA1TCCA1TGCG-3':3'-CG GGT1AGGT1ACGC-5'), and duplex-III (5'-GCTCCA11TGCACCG-3':3'-CGAG GT11ACGTGGC-5'). In the presence of Cu(II) or Ni(II) ions, duplex-I and duplex-II, which contain isolated 1-1 pair(s), were stabilized. In contrast, duplex-III, which contained consecutive 1-1 pairs, was stabilized significantly in the presence of Cu(II) ions, while the addition of Ni(II) ions had no notable effect on its thermal denaturation profile.

Hybridization-promoted and cytidine-selective activation for cross-linking with the use of 2-amino-6-vinylpurine derivatives.

Recently, we have proposed a new concept for cross-linking agents with inducible reactivity, in which the highly reactive cross-linking agent, the 2-amino-6-vinylpurine nucleoside analogue (1), can be regenerated in situ from its stable precursors, the phenylsulfide (4) and the phenylsulfoxide (3) derivatives, by a hybridization-promoted activation process with selectivity to cytidine. The phenylsulfide precursor (4) exhibited cross-linking ability despite its high stability toward strong nucleophiles such as amines and thiols. In this study, we investigated the substituent effects of the phenylsulfide group on the cross-linking reaction, and determined the 2-carboxy substituent of the phenylsulfide derivative (11k) as an efficient cross-linking agent with inducible reactivity. Detailed investigations have shown that the phenylsulfoxide (3) and phenylsulfide (4) precursors produce the 2-amino-6-vinylpurine nucleoside (1) as the common reactive species. It has been concluded that the nature of the inducible reactivity of the precursors (3 and 4) is acceleration of their elimination to the 2-amino-6-vinylpurine nucleoside (1) through the selective process in the duplex with the ODN having cytidine at the target site.