A long-term survival case of local recurrence of breast cancer treated with combined modality therapy

The case was a 70-year-old woman. In 1997, the patient underwent pectoral muscle-preserving mastectomy and axillary/subclavicular lymph node dissection for the treatment of right breast cancer. Histological diagnosis was invasive ductal carcinoma (T2, N2, M0, Stage IIIA). She received a combination therapy with TAM and UFT for 5 years postoperatively. Because tumor recurrence occurred in right axillary lymph nodes in the 9th postoperative year, the patient underwent resection of these lymph nodes followed by 6 cycles of AC-based chemotherapy. Multiple lung metastases occurred in the 10th postoperative year, and then, the patient received 8 cycles of DOC-based chemotherapy. In the 11th postoperative year, a mass appeared again in the right axilla, and 6 cycles of capecitabine-based chemotherapy was administered. In the 12th postoperative year, pulmonary metastasis was in progression and an increased right axillary mass were noted. Thus, the specimen extirpated in 2006 was examined again, revealing negative ER, negative PgR and positive HER2. Six cycles of combined trastuzumab+PTX therapy were administered. Lung metastasis decreased in size, allowing a judgment of partial response. Because the right axillary mass had grown to 10 cm, and the patient's QOL was reduced, it was extirpated. The patient is scheduled to receive a postoperative radiotherapy, followed by resumption of chemotherapy.     

Epithelial–mesenchymal transition in cancer development and its clinical significance

The epithelial–mesenchymal transition (EMT) plays a critical role in embryonic development. EMT is also involved in cancer progression and metastasis and it is probable that a common molecular mechanism is shared by these processes. Cancer cells undergoing EMT can acquire invasive properties and enter the surrounding stroma, resulting in the creation of a favorable microenvironment for cancer progression and metastasis. Furthermore, the acquisition of EMT features has been associated with chemoresistance which could give rise to recurrence and metastasis after standard chemotherapeutic treatment. Thus, EMT could be closely involved in carcinogenesis, invasion, metastasis, recurrence, and chemoresistance. Research into EMT and its role in cancer pathogenesis has progressed rapidly and it is now hypothesized that novel concepts such as cancer stem cells and microRNA could be involved in EMT. However, the involvement of EMT varies greatly among cancer types, and much remains to be learned. In this review, we present recent findings regarding the involvement of EMT in cancer progression and metastasis and provide a perspective from clinical and translational viewpoints. (Cancer Sci 2009)     

Polycomb group molecule PHC3 regulates polycomb complex composition and prognosis of osteosarcoma

Polyhomeotic homolog 3 (PHC 3) is a member of the human polycomb complex and has been regarded as a candidate tumor suppressor of osteosarcoma. In the present paper, we performed a mutation survey and PHC3 expression analysis by quantitative real‐time PCR using 10 osteosarcoma cell lines and 42 primary osteosarcoma samples. Relative PHC3 expression values of clinical samples were analyzed with clinical outcomes, and it was suggested that lower PHC3‐expressing patients had significantly worse overall survival. Relative PHC3 values of clinical samples were less than those of normal bone tissues, whereas they were greater than those of cell lines. By denaturing high performance liquid chromatography analysis and direct sequencing, we found a PHC3 missense mutation in U2OS cells, which resulted in arginine56 to proline substitution. The same point mutation existed in four of 42 primary osteosarcoma samples. Regarding functional analysis, PHC3 expression significantly suppressed the colony formation of tumor cells. Intriguingly, polycomb repressive complex 1 members, Bmi1 and Ring1b proteins, were reduced in PHC3‐expressing osteosarcoma cells. Deletion mutant PHC3 expression suggested that the carboxyl terminus of PHC3 has a role in suppression; the above‐mentioned point mutation of PHC3 also lost inhibitory activities. Conversely, Bmi1 expression reduced PHC3 at the mRNA level and induced the proliferation of osteosarcoma cells. Taken together, we confirmed the role of PHC3 as a tumor suppressor in osteosarcoma cells and found that PHC3‐dependent tumor suppression may be caused by modification of the composition of polycomb repressive complex 1 in cancer cells. (Cancer Sci 2010)     

Rare Influenza A (H3N2) Variants with Reduced Sensitivity to Antiviral Drugs

In 2007 and 2008 in Myanmar, we detected influenza viruses A (H3N2) that exhibited reduced sensitivity to both zanamivir and amantadine. These rare and naturally occurring viruses harbored a novel Q136K mutation in neuraminidase and S31N mutation in M2.     

Implications of greater short-term PSA recurrence with laparoscopic as compared to retropubic radical prostatectomy for Japanese clinically localized prostate carcinomas

Purpose: There is ongoing discussion as to the necessity for certain surgical procedures being limited to high through-put institutions. To cast light on this question regarding use of open as compared to laparoscopic radical prostatectomy (LRP) the present study was conducted focusing on biochemical (PSA) recurrence-free survival of Japanese patients with clinically localized prostate carcinomas. Materials and Methods: From April 2004 to December 2010 we identified 579 patients undergoing LRP (n=245) and retropubic radical prostatectomy (RRP) (n=334) who did not undergo immediate adjuvant therapy (radiation and/or hormonal) and whose PSA levels were lower than 25 ng/ml. Preoperative prostate specific antigen (PSA) level, clinical stage, biopsy Gleason score and pathological features were assessed and Kaplan-Meier estimates of biochemical recurrence (BCR)-free survival were compared. A Cox regression model analysis was performed to determine predictors of biochemical recurrence. Results: Median follow up was 35 months(2- 115). On univariate analysis the LRP group had a slightly lower pathological T stage (p<0.001), higher biopsy Gleason score (p<0.001), but much more organ confined disease (p=0.001) than the RRP group. BCR-free survival did not significantly differ between LRP and RRP groups with preoperative PSA <6, clinical stage T1c,T2a, pathological stage T3 or more, biopsy Gleason score of 8 or more, pathological Gleason score of 6 or less and 8 or more, extra-capsular extension and negative surgical margin. The 3-year BCR-free survival rates were 91.0%(RRP) and 82.2%(LRP) (p<0.001). Conclusion: We conclude that in general LRP may be associated with a less positive outcome than BCR for resection of low risk prostate cancers. Therefore indications for LRP should be very carefully monitored.     

Role of estrogen receptors and aromatase on brain protein synthesis rates in ovariectomized female rats fed genistein

We have reported that the dietary addition of genistein, a phytoestrogen found abundantly in soy products, stimulates brain protein synthesis rates of ovariectomized female rats. In the present study, we determine whether stimulation of brain protein synthesis rates in ovariectomized female rats by the dietary addition of genistein was conducted via estrogen receptors and aromatase-mediating actions. After ovariectomy, Wistar female rats were treated with genistein, the estrogen receptor antagonist ICI 182,780, and/or fadrozole a systemic aromatase inhibitor. In the cerebral cortex, the cerebellum and the hypothalamus, the fractional (Ks) rates of protein synthesis were increased by the dietary addition of genistein. These effects of genistein were inhibited by the administration of ICI 182,780 and fadrozole. However, the degrees to which ICI 182,780 and fadrozole inhibited the effects of genistein differed depending on the brain region. This result suggests that dietary genistein elevates the rate of protein synthesis in the brain of ovariectomized female rats. In addition, the estrogen receptors of the brain and the aromatase of the peripheral tissue and brain are, at least partly, related to the rate of brain protein synthesis caused by genistein.