Neoadjuvant chemotherapy with cisplatin, aclacinomycin A, and mitomycin C for cervical adenocarcinoma – a preliminary study

Between 1989 and 2002, 28 patients with locally advanced cervical adenocarcinoma (bulky IB-IIIB) were recruited for a pilot study aimed at evaluation of the effectiveness of neoadjuvant chemotherapy with cisplatin, aclacinomycin-A, and mitomycin-C (PAM), followed by radical surgery. This regimen was administrated intra-arterially or intravenously. In addition to patients treated with PAM, we retrospectively analyzed the prognoses of 26 patients in stage I and II, who had been treated between 1975 and 1981 with radical surgery with/without radiation therapy. Twenty-eight patients received PAM therapy as neoadjuvant chemotherapy, and 75.0% of the 16 intra-arterially infused patients showed a response, as did 66.7% of the 12 intravenously infused patients. There was a significant difference in the 5-year prognosis of stage II (PAM group, 72.9%; without-PAM group, 36.4%). The results suggest that, as the free space in the parametrium is widened by neoadjuvant chemotherapy with PAM, it is possible that the tumor could be completely resected by radical hysterectomy. Thus, neoadjuvant chemotherapy with PAM is expected to improve the survival rate of patients with advanced cervical adenocarcinoma by the preliminary study. However, the survival rates of stage II with lymph node metastasis in the without-PAM group seem low, and we must also consider that the various technologies to evaluate and treat the cervical adenocarcinomas, e.g. computed tomography, magnetic resonance imaging, and surgical equipments, had improved during 1989-2002 than was the scenario during 1975-1981, and these improvements contributed to better prognosis. A prospective-randomized study is needed to assess the value of this approach compared with standard management.     

Case report: Two successful pregnancies following the transfer of re-vitrified human day 7 blastocysts developed from vitrified cleaved embryos

PURPOSE: To report successful pregnancies after the transfer of re-vitrified human day 7 blastocysts developed from vitrified cleaved embryos. METHODS AND RESULTS: A total of five day 7 blastocysts developed from vitrified cleaved embryos were re-vitrified and re-warmed. All of five re-vitrified day 7 blastocysts (100%) survived after warming and were transferred to three patients. Two of the women became clinically pregnant. Of these women, one woman delivered a healthy baby and the other pregnancy is ongoing at 26 weeks of gestation. CONCLUSIONS: This is the first report of successful pregnancies after the transfer of re-vitrified human day 7 blastocysts developed from vitrified cleaved embryos.     

Precise immunological evaluation rationalizes the design of a self-adjuvanting vaccine composed of glycan antigen,TLR1/2 ligand,and T-helper cell epitope

Sialyl-Tn (STn), overexpressed on various tumors, has been investigated for its application in anti-cancer vaccine therapy. However, Theratope, an STn-based vaccine, failed in the phase III clinical trial due to poor immunogenicity and epitope suppression by the foreign carrier protein. We therefore developed a self-adjuvanting STn based-vaccine, a conjugate of clustered STn (triSTn) antigen, TLR1/2 ligand (Pam₃CSK₄), and T-helper (Th) cell epitope, and found that this three-component self-adjuvanting vaccine effectively resulted in the production of anti-triSTn IgG antibodies. We herein analyzed immune responses induced by this self-adjuvanting vaccine in detail. We newly synthesized two-component vaccines, i.e., Pam₃CSK₄- or Th epitope-conjugated triSTn, as references to evaluate the immune-stimulating functions of Pam₃CSK₄ and Th epitope. Immunological evaluation of the synthesized vaccine candidates revealed that Pam₃CSK₄ was essential for antibody production, indicating that the uptake of triSTn antigen by antigen-presenting cells (APCs) was promoted by the recognition of Pam₃CSK₄ by TLR1/2. The function of the Th epitope was also confirmed. Th cell activation was important for boosting antibody production and IgG subclass switching. Furthermore, flow cytometric analyses of immune cells, including T cells, B cells, dendritic cells, and other monocytes, were first employed in the evaluation of self-adjuvanting vaccines and revealed that the three-component vaccine was able to induce antigen-specific immune responses for efficient antibody production without excessive inflammatory responses. Importantly, the co-administration of Freund''s adjuvants was suggested to cause excessive myeloid cell accumulation and decreased plasma cell differentiation. These results demonstrate that vaccines can be designed to achieve the desired immune responses via the bottom-up construction of each immune element.

Detailed analysis of a three-component self-adjuvanting vaccine revealed that conjugate vaccines can be designed to achieve the desired immune responses via bottom-up construction of the necessary immune elements.     

Transposon-like sequences in extrachromosomal circular DNA from mouse thymocytes.

Small polydisperse circular (spc) DNA was isolated from mouse thymocytes and cloned into the HindIII site of lambda vector Charon 7. Fifty-six recombinants from this spc DNA library were analyzed. R repeats, which were originally found near immunoglobulin genes, were enriched in spc DNA clones relative to their representation in the chromosome. In one clone, the R sequence was linked to Bam and MIF sequences and the contiguous arrangement was truncated from both ends. In another clone, composite Bam/R and R repeats existed as a pair in inverted repeat orientation. Truncation occurred from the 5' side without affecting the 3' ends. In both clones, short direct repeats flanked the repeated sequences. The possible role of R sequences in transposition and circular formation is discussed.     

Anomalous systemic arterial supply to normal basal segments of the left lower lobe.

BACKGROUND: Anomalous arterial supply to the normal basal segments of the lower lobe without sequestration is a rare congenital abnormality, and whether it belongs to the broad spectrum of sequestration disorders remains controversial. METHODS: The cases of all 4 patients who were treated surgically by us were reviewed together with 8 previously reported cases. RESULTS: The anomalous artery originated from the descending thoracic aorta, distributed to the basal segments of the left lower lobe, and drained to a normal inferior pulmonary vein in each case. The anomalous artery was thick and elastic walled. From the review of all 12 cases, male gender, left side, descending thoracic aorta as the aberrant arterial origin, absence of pulmonary blood flow to the basal segments, and normal pulmonary venous drainage were predominant. Despite some differences, the findings seemed closely related to intralobar sequestration. Surgical treatments were lung resection, anastomosis, and ligation of the anomalous artery. CONCLUSIONS: This anomaly is probably one type of sequestration complex. Both aortic and pulmonary arterial angiographic studies are needed to plan the definitive surgical procedure.     

Glomerular hypertrophy in preeclamptic patients with focal segmental glomerulosclerosis. A morphometric analysis

BACKGROUND: Focal segmental glomerulosclerotic lesion (FSGS lesion) is frequently observed in preeclamptic patients with nephrotic syndrome. PATIENTS AND METHODS: We performed a morphometric analysis of renal biopsies from 20 patients with severe preeclampsia to evaluate the pathogenetic role of glomerular hypertrophy in preeclamptic nephropathy associated with FSGS lesion. We also analyzed biopsies obtained from 6 preeclamptic patients without FSGS lesion and 10 patients with isolated hematuria. Nonsclerotic glomeruli were examined. RESULTS: The mean glomerular tuft area (GTA), the whole glomerular area (WGA), and the extracellular matrix area (EMA) were significantly and negatively correlated with the postpartum day at biopsy in preeclamptic patients with FSGS lesion who underwent renal biopsy within 40 days after delivery. The mean GTA, WGA, EMA and number of mesangial cells (MN) were significantly increased in preeclamptic patients with FSGS lesion compared with patients with isolated hematuria and compared with those without FSGS lesion when the biopsy time was matched between patients with and without FSGS lesion. The GTA and WGA were not different between preeclamptic patients without FSGS lesion and patients with isolated hematuria. CONCLUSION: These results support the assumption that glomerular hypertrophy that develops during severe toxemic pregnancy plays an important role in the pathogenesis of FSGS lesion and is reversible about 40 days after delivery.