Expression of occ1 mRNA in the visual cortex during postnatal development in macaques

We previously reported that the occ1 gene is specifically expressed in the primary visual cortex of adult monkeys in an activity-dependent manner (Tochitani et al., Eur. J. Neurosci., 3, 297-307, 2001). In this report, we compared occ1 mRNA expression in the primary visual cortex during the development of newborn, 3-month-old and adult monkeys. occ1 mRNA was already expressed preferentially in the primary visual cortex of newborn monkeys, but the laminar pattern of occ1 expression in the visual cortex changed as development proceeded. This suggests the possible importance of experience-dependent developmental regulations of occ1 in the developing primary visual cortex.     

Optimal scanning timing by use of multi-detector row computed tomography during thoracic aortography for depiction of arteries causing hemoptysis

Scanning timing for multi-detector row computed tomography during thoracic aortography (MDCT-TA) was explored for depiction of arteries responsible for hemoptysis. The mean time (MT) from contrast medium (CM) injection to peak enhancement (PE) in the descending aorta at the level of the diaphragm on thoracic aortography was investigated. The MT to PE of the descending aorta at the level of diaphragm was 4.86 ± 0.42 s, with 30 mL CM at an injection rate of 10 mL/s. CM injection was completed 1.86 s before the final slice was obtained. The CM injection duration can be calculated as follows: 4.86 s + scan time ? 1.86 s. The optimal scanning timing is a scan delay of approximately 5 s from the start of CM injection, and the CM injection duration is expressed as scan time plus 3 s. MDCT-TA depicted the branching sites of the bronchial arteries in all cases.     

Prostate-supplying arteriogram created by multidetector-row CT during pelvic arteriography: contribution to the treatment strategy of prostatic artery embolization for prostatic hyperplasia

We describe an 85-year-old man suffering lower urinary tract symptoms, who underwent prostatic artery embolization (PAE) based on a prostate-supplying arteriogram created with multidetector-row computed tomography during pelvic arteriography. This arteriogram was synthesized from a background bone volume-rendered (VR) image, an aorta–pelvic artery VR image, and a prostate-supplying artery VR image. Because the bone background VR image is combined with the aorta–pelvic artery VR image, the prostate-supplying arteriogram can simultaneously show the pelvic branch arteries present on the ventral side, inside, and the dorsal side of the pelvic bone. It showed that the left prostatic artery supplied the urethra at the outlet of the urinary bladder. PAE of the left prostatic artery was performed with catheter navigation based on the prostate-supplying arteriogram. There was marked relief of the lower urinary tract symptoms at the 12-month follow-up.     

Arterial stiffness in predialysis patients with uremia

BACKGROUND: Hemodialysis patients have advanced arterial wall stiffening as shown by increased aortic pulse wave velocity (PWV), an independent predictor of cardiovascular mortality. We compared aortic PWV of uremic patients before starting hemodialysis treatment with that of patients on maintenance hemodialysis. METHODS: The subjects were 71 patients with end-stage renal disease (ESRD) before starting hemodialysis (predialysis group), 144 patients on maintenance hemodialysis, and 140 healthy control subjects. These three groups were all nondiabetic and comparable in age and gender. RESULTS: The hemodialysis group had greater aortic PWV than the healthy subjects, and the predialysis patients showed a still higher value than the hemodialysis group. Multiple regression analysis in the total subjects revealed that the presence of renal failure was significantly associated with increased aortic PWV independent of age, gender, blood pressure, body mass index, smoking, high-density lipoprotein (HDL) and nonhigh-density lipoprotein (non-HDL) cholesterol levels. In contrast, hemodialysis was associated with decreased aortic PWV independent of renal failure and the other factors. Further analyses in the combined uremic patients again indicated the favorable impact of hemodialysis on aortic PWV independent of the classical risk factors, use of antihypertensive medications, including angiotensin-converting enzyme inhibitors and calcium channel blockers, hematocrit, serum calcium, phosphorus, parathyroid hormone levels, and the use of calcium carbonate. Insulin resistance using homeostasis model assessment (HOMA-IR) was associated with increased aortic PWV. CONCLUSION: Aortic stiffening was present in uremic patients before starting hemodialysis treatment and no adverse effect of hemodialysis was observed, suggesting the important roles of renal failure and/or metabolic alterations secondary to renal failure in arterial stiffness in patients with uremia.     

Feasibility of extended-field irradiation and intracavitary brachytherapy combined with weekly cisplatin chemosensitization for IB2–IIIB cervical cancer with positive paraaortic or high common iliac lymph nodes: a retrospective review

Background

The aim of this retrospective study was to investigate the feasibility of primary treatment with extended-field irradiation and weekly cisplatin (extended-field concurrent chemoradiotherapy, EFCCRT) as initial therapy in patients with International Federation of Gynecology and Obstetrics IB1 to IIIB cervical cancer with paraaortic or high common iliac lymph node metastases.

Methods

Participants comprised patients with confirmed cervical cancer, showing paraaortic or high common iliac lymph node metastases on diagnostic imaging, treated with EFCCRT. Total external radiation doses were 50.4 Gy to the whole pelvis and 45.0 Gy to the lumbar paraaortic region. High-dose-rate intracavitary brachytherapy was performed to deliver a total dose of 18–24 Gy in 6-Gy fractions prescribed at point A. Weekly cisplatin (30–40 mg/m²) was given concurrently with radiotherapy.

Results

Twenty-four patients were treated. Median follow-up interval was 34 months. The dose of cisplatin was 30 mg/m² in 2 cases, 35 mg/m² in 8 cases, and 40 mg/m² in 14 cases. Twenty-two cases (92 %) received more than 160 mg/m² cisplatin. Ten cases (42 %) experienced acute grade 3/4 hematological toxicity, and 9 cases (38 %) experienced acute grade 3 nonhematological toxicity. No case presented late grade 3/4 toxicity. Three-year progression-free and overall survival rates were 54 % and 72 %, respectively. Eleven cases recurred during follow-up. Sites of recurrence were within the irradiation field in 4 cases, outside the field in 6 cases, and in both fields in 1 case.

Conclusion

EFCCRT and high-dose-rate intracavitary brachytherapy for patients with paraaortic or high common iliac lymph node metastases from cervical cancer is feasible.     

Novel retinoblastoma mutation abrogating the interaction to E2F2/3, but not E2F1, led to selective suppression of thyroid tumors

Mutant mouse models are indispensable tools for clarifying gene functions and elucidating the pathogenic mechanisms of human diseases. Here, we describe novel cancer models bearing point mutations in the retinoblastoma gene (Rb1) generated by N‐ethyl‐N‐nitrosourea mutagenesis. Two mutations in splice sites reduced Rb1 expression and led to a tumor spectrum and incidence similar to those observed in the conventional Rb1 knockout mice. The missense mutant, Rb1^D326V/+, developed pituitary tumors, but thyroid tumors were completely suppressed. Immunohistochemical analyses of thyroid tissue revealed that E2F1, but not E2F2/3, was selectively inactivated, indicating that the mutant Rb protein (pRb) suppressed thyroid tumors by inactivating E2F1. Interestingly, Rb1^D326V/+ mice developed pituitary tumors that originated from the intermediate lobe of the pituitary, despite selective inactivation of E2F1. Furthermore, in the anterior lobe of the pituitary, other E2F were also inactivated. These observations show that pRb mediates the inactivation of E2F function and its contribution to tumorigenesis is highly dependent on the cell type. Last, by using a reconstitution assay of synthesized proteins, we showed that the D326V missense pRb bound to E2F1 but failed to interact with E2F2/3. These results reveal the effect of the pRb N‐terminal domain on E2F function and the impact of the protein on tumorigenesis. Thus, this mutant mouse model can be used to investigate human Rb family‐bearing mutations at the N‐terminal region.     

High antitumor activity of pladienolide B and its derivative in gastric cancer

The antitumor activity of pladienolide B, a novel splicing inhibitor, against gastric cancer is totally unknown and no predictive biomarker of pladienolide B efficacy has been reported. We investigated the antitumor activity of pladienolide B and its derivative on gastric cancer cell lines and primary cultured cancer cells from carcinomatous ascites of gastric cancer patients. The effect of pladienolide B and its derivative on six gastric cancer cell lines was investigated using a MTT assay and the mean IC₅₀ values determined to be 1.6 ± 1.2 (range, 0.6–4.0) and 1.2 ± 1.1 (range, 0.4–3.4) nM, respectively, suggesting strong antitumor activity against gastric cancer. The mean IC₅₀ value of pladienolide B derivative against primary cultured cells from 12 gastric cancer patients was 4.9 ± 4.7 nM, indicative of high antitumor activity. When 18 SCID mice xenografted with primary cultured cells from three patients were administered the pladienolide B derivative intraperitoneally, all tumors completely disappeared within 2 weeks after treatment. Histological examination revealed a pathological complete response for all tumors. In the xenograft tumors after treatment with pladienolide B derivative, immature mRNA were detected and apoptotic cells were observed. When the expressions of cell‐cycle proteins p16 and cyclin E in biopsied gastric cancer specimens were examined using immunohisctochemistry, positivities for p16 and cyclin E were significantly and marginally higher, respectively, in the low‐IC₅₀ group compared with the high‐IC₅₀ group, suggesting the possibility that they might be useful as predictive biomarkers for pladienolide B. In conclusion, pladienolide B was very active against gastric cancer via a mechanism involving splicing impairment and apoptosis induction.