Development of a new coordinate calibration phantom for a light-section-based optical surface monitoring system.

A calibration phantom made of Derlin requires manual translational and rotational adjustments when calibrating a light-section-based optical surface monitoring system (VOXELAN) with a phantom material that insufficiently reflects the red-slit laser of the system. This study aimed to develop a new calibration phantom using different materials and to propose a procedure that minimizes setup errors. The new phantom, primarily made of PET100, which exhibits good reflectivity without scattering or attenuating the red-slit laser at the phantom surface, was shaped in a manner similar to that of previous designs. The detection accuracy and stability were evaluated using six different regions of interest (ROIs) and compared with previous phantom designs. The coordinate coincidence between the machine and VOXELAN was compared for both phantom designs. The detection accuracy and stability of the new phantom in the reference ROI setting were found to be better than those of previous phantoms. In the lateral, longitudinal, and vertical directions, the coordinate coincidences in translational directions for the previous phantom were obtained at 1.07 ± 0.66, 1.46 ± 0.47, and 0.26 ± 0.83 mm, whereas those for the new phantom were obtained at 0.28 ± 0.21, 0.18 ± 0.30, and - 0.30 ± 0.29 mm, respectively. The rotational errors of the two phantoms were identical. The new phantom exhibited improved detection stability because of its good reflectivity. Additionally, the new placement procedure was linked to the six-degrees-of-freedom couch. A combination of the new phantom and its new placement procedure is suitable for coordinate calibration of VOXELAN.

The efficacy of a third-generation oncolytic herpes simplex viral therapy for an HPV-related uterine cervical cancer model.

PURPOSE: Cervical cancer is the fourth most common cancer in women and the seventh most common of all human cancers. Development of new treatments is mandatory to improve the outcome of this disease. Replication-selective oncolytic herpes simplex viruses (HSVs) have emerged as a new platform for cancer therapy. The therapeutic potential of a triple-mutated oncolytic HSV (T-01) for human papillomavirus (HPV)-related cervical cancer was evaluated with immunodeficient and immune-complete models. METHODS: (1) The in vitro efficacy of T-01 on human cervical cancer cell lines, TC-1, HeLa, CaSki, and SKG IIIa was evaluated. (2) The in vivo efficacy of T-01 was examined in human HeLa xenograft and TC-1 syngeneic models of human cervical cancer. After flank tumors reached 5 mm in diameter, the first intratumoral (i.t.) administration of T-01 was performed. Intratumoral administration of T-01 was performed with a 5 day interval a total of 6 times. RESULTS: In the in vitro study, T-01 was highly cytotoxic for all cell lines (48 h after infection with T-01 at 1 × 105 PFU, T-01 killing HeLa: 67.5%, Caski: 62.8%, SKG IIIa: 43.2%). Furthermore, in the human HeLa xenograft and TC-1 syngeneic models, T-01 resulted in a significant reduction of tumor growth. In addition, tumor-bearing mice treated with T-01 showed significantly increased numbers of CD8 + T-cells precursors than the control mice (p = 0.03). CONCLUSIONS: These results demonstrate that T-01 has cytotoxic efficacy and inhibited against HPV-related cervical cancer cells. These findings indicate that T-01 has therapeutic potential for HPV-related cervical cancer.

A case of primary ovarian signet-ring cell carcinoma treated with S-1/CDDP therapy.

BACKGROUND: Primary ovarian signet-ring cell carcinoma is extremely rare, with only five recent case reports. Almost all reported cases of ovarian signet-ring cell carcinoma have been treated with TC therapy and none have reported regarding the use of S-1/CDDP therapy. We report a case of primary ovarian signet-ring cell carcinoma treated postoperatively with S-1/CDDP therapy. CASE PRESENTATION: We describe a 55-year-old woman diagnosed with stage IB primary ovarian signet-ring cell carcinoma that was treated with S-1/CDDP therapy. Preoperative transvaginal ultrasonography and contrast-enhanced computed tomography (CT) revealed a solid tumor measuring 10 cm in diameter in the pelvis. The tumor marker levels were as follows: CA125, 41.6 U/mL; CA19-9, < 2.0 U/mL; and CEA, 2.2 ng/mL. Ovarian cancer was suspected, and total abdominal hysterectomy, bilateral salpingo-oophorectomy, and omentectomy were performed. The left ovary was enlarged to greater than fist-sized, and there was a small amount of clear yellow ascites. Histological examination of the left ovary led to the diagnosis of signet-ring cell carcinoma. Histological examination of the right ovary also showed the presence of a signet-ring cell carcinoma. After surgery, upper and lower gastrointestinal endoscopy and positron-emission tomography-CT were performed to search for a possible primary lesion, but none was found. The patient was diagnosed with primary ovarian signet-ring cell carcinoma with FIGO Stage IB (PT1b, NX, M0). As postoperative adjuvant chemotherapy, S-1/CDDP therapy (S-1120 mg/day/body × 14 days, CDDP 50 mg/m2 day 8, q 21 days) was administered for six cycles. There was no recurrence 27 months after the initial treatment. CONCLUSIONS: We considered S-1/CDDP therapy was effective for primary ovarian signet-ring cell carcinoma. This is the first case report of primary ovarian signet-ring cell carcinoma treated with S-1/CDDP therapy in the world.

The Responses of Arabidopsis Early Light-Induced Protein2 to Ultraviolet B, High Light, and Cold Stress Are Regulated by a Transcriptional Regulatory Unit Composed of Two Elements.

The Arabidopsis (Arabidopsis thaliana) Early Light-Induced Protein (ELIP) is thought to act as a photoprotectant, reducing the damaging effects of high light (HL). Expression of ELIP2 is activated by multiple environmental stresses related to photoinhibition. We have identified putative regulatory elements in an ELIP2 promoter using an octamer-based frequency comparison method, analyzed the role of these elements using synthetic promoters, and revealed a key transcriptional regulatory unit for ultraviolet B (UV-B) radiation, HL, and cold stress responses. The unit is composed of two elements, designated as Elements A (TACACACC) and B (GGCCACGCCA), and shows functionality only when paired. Our genome-wide correlation analysis between possession of these elements in the promoter region and expression profiles in response to UV-B, HL, and cold suggests that Element B receives and integrates these multiple stress signals. In vitro protein-DNA binding assays revealed that LONG HYPOCOTYL5 (HY5), a basic domain-Leucine zipper transcription factor, directly binds to Element B. In addition, mutant analysis of HY5 showed partial involvement in the UV-B and HL responses but not in the cold stress response. These results suggest that signals for UV-B, HL, and cold stress join at Element B, which recognizes the signals of multiple transcription factors, including HY5.

SENSITIVE TO PROTON RHIZOTOXICITY1, CALMODULIN BINDING TRANSCRIPTION ACTIVATOR2, and other transcription factors are involved in ALUMINUM-ACTIVATED MALATE TRANSPORTER1 expression.

In Arabidopsis (Arabidopsis thaliana) the root apex is protected from aluminum (Al) rhizotoxicity by excretion of malate, an Al chelator, by ALUMINUM-ACTIVATED MALATE TRANSPORTER1 (AtALMT1). AtALMT1 expression is fundamentally regulated by the SENSITIVE TO PROTON RHIZOTOXICITY1 (STOP1) zinc finger protein, but other transcription factors have roles that enable Al-inducible expression with a broad dynamic range. In this study, we characterized multiple cis-elements in the AtALMT1 promoter that interact with transcription factors. In planta complementation assays of AtALMT1 driven by 5' truncated promoters of different lengths showed that the promoter region between -540 and 0 (the first ATG) restored the Al-sensitive phenotype of atalm1 and thus contains cis-elements essential for AtALMT1 expression for Al tolerance. Computation of overrepresented octamers showed that eight regions in this promoter region contained potential cis-elements involved in Al induction and STOP1 regulation. Mutation in a position around -297 from the first ATG completely inactivated AtALMT1 expression and Al response. In vitro binding assays showed that this region contained the STOP1 binding site, which accounted for the recognition by four zinc finger domains of the protein. Other positions were characterized as cis-elements that regulated expression by repressors and activators and a transcription factor that determines root tip expression of AtALMT1. From the consensus of known cis-elements, we identified CALMODULIN-BINDING TRANSCRIPTION ACTIVATOR2 to be an activator of AtALMT1 expression. Al-inducible expression of AtALMT1 changed transcription starting sites, which increased the abundance of transcripts with a shortened 5' untranslated region. The present analyses identified multiple mechanisms that regulate AtALMT1 expression.

Neoadjuvant chemotherapy using platinum- and taxane-based regimens for bulky stage Ib2 to IIb non-squamous cell carcinoma of the uterine cervix.

PURPOSE: There are no reports on the use of neoadjuvant chemotherapy (NAC) in non-squamous cell cervical carcinoma. We examined the effectiveness and safety of paclitaxel/carboplatin (TC) and docetaxel/carboplatin (DC). METHODS: Stage Ib2 to IIb disease was present in 23 patients scheduled for radical hysterectomy. We administered 1-3 courses of either the TC or the DC regimen. Anti-tumor effects were found superior by Response Evaluation Criteria in Solid Tumors. Safety was assessed with National Cancer Institute Common Terminology Criteria for Adverse Events. RESULTS: Median age was 50 years (range 32-63 years), with stage Ib2 in 6 cases (26.1%) and IIb in 17 cases (73.9%). Complete response was achieved in 5 cases (21.7%), partial response in 13 (56.5%), stable disease in 5 (21.7%); the response rate was 78.3%, and surgery completion rate was 78.3%. Leukopenia or neutropenia ≥grade 3 was seen in 12 (52.2%) and 21 (91.3%) cases, respectively, with grade 3 febrile neutropenia in 2 cases (8.7%) and no anemia or thrombocytopenia ≥grade 3. Median progression-free survival was 26 months (95% Cl, 13.5-38.5 months); median overall survival was 35 months (95% Cl, 20.9-49.1 months). CONCLUSION: NAC for non-squamous cell cervical carcinoma showed potent anti-tumor effects and manageable adverse events.

Skin advanced glycation end product accumulation and muscle strength among adult men.

Aging is associated with decreased skeletal muscle function. Increased levels of advanced glycation end products (AGEs) in skeletal muscle tissue are observed with advancing age and in diabetes. Although serum AGE level is negatively associated with grip strength in elderly people, it is unknown whether this association is present in adult males. To determine the relationship between AGE accumulation in tissue and muscle strength and power among Japanese adult men. Skin autofluorescence (AF) (a noninvasive method for measuring tissue AGEs), grip strength (n = 232), and leg extension power (n = 138) were measured in Japanese adult men [median (interquartile range) age, 46.0 (37.0, 56.0) years]. After adjustment for potential confounders, the adjusted means [95% confidence interval (CI)] for grip strength across the tertiles of skin AF were 44.5 (43.2, 45.9) kg for the lowest tertile, 42.0 (40.6, 43.3) kg for the middle tertile, and 41.7 (40.3, 43.1) kg for the highest tertile (P for trend < 0.01). Moreover, the adjusted geometric means (95% CI) of leg extension power across the tertiles of skin AF were 17.8 (16.6, 19.1) W/kg for the lowest tertile, 17.5 (16.4, 18.7) W/kg for the middle tertile, and 16.0 (14.9, 17.1) W/kg for the highest tertile (P for trend = 0.04). Among Japanese adult men, participants with higher skin AF had lower muscle strength and power, indicating a relationship between AGE accumulation and muscle strength and power. A long-term prospective study is required to clarify the causality.