false-positive results of human chorionic gonadotropin β measurement after high orchiectomy for stage i seminoma: report of a case

A 21-year-old male presented at our hospital with a complaint of left scrotal swelling. The serum human chorionic gonadotropin-β (hCG-β) level was 1.3 ng/ml. A left high orchitectomy was performed, and a histological study demonstrated seminoma. Computerized tomography showed no evidence of metastasis. Adjuvant radiation therapy with 25 Gy was performed for stage I seminoma. Although complete clinical remission was achieved,the hCG-β level remained slightly positive (0.3-0.5 ng/ml). The urine hCG-β-core fragment was determined to be within normal limits. This confirmed that the result of serum hCG-β measurement was false-positive in our case. The patient received no additional treatment, and is free from recurrence 3 years and 1 month after surgery. In the testicular germ cell tumors,the measurement of urine hCG-β-core fragment is useful for differential diagnosis in cases of low level-positive serum hCG-β without clinical evidence of disease.     

Standard therapy for glioblastoma--a review of where we are

Glioblastoma is the most common primary malignant brain tumor in adults and is a challenging disease to treat. The current standard therapy includes maximal safe surgical resection, followed by a combination of radiation and chemotherapy with temozolomide. However, recurrence is quite common, so we continue to search for more effective treatments both for initial therapy and at the time of recurrence. This article will review the current standard of care and recent advances in therapy for newly-diagnosed and recurrent glioblastomas, based on the most authoritative guidelines, the National Cancer Institute's comprehensive cancer database Physician Data Query (PDQ?), and the National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology(TM) for central nervous system cancers (V.1.2010), to elucidate the current position and in what direction we are advancing.     

Correlation and association of plasma interleukin-6 and plasma platelet-derived microparticles, markers of activated platelets, in healthy individuals

Intorduction

The aim of this study was to clarify the correlation and association of plasma IL-6 and PDMPs, both of which are associated with metabolic syndrome, in healthy individuals.

Materials and Methods

We conducted a cross-sectional study of 464 healthy Japanese volunteers (210 men and 254 women, median age 39 and 35 years, respectively) who had no signs, symptoms or history of cardiovascular- or cerebrovascular disease and took no medications. We assayed their IL-6 levels with a conventional ELISA kit and their PDMP levels by ELISA and monoclonal antibodies against CD42b and CD42a (glycoprotein Ib and IX).

Results

By multivariate analysis, the plasma level of PDMP was correlated with diastolic blood pressure (p = 0.015), platelet count (p < 0.001), high sensitivity C-reactive protein, and the plasma level of IL-6 (p < 0.001) in men (R² = 0.454, p < 0.001) and was correlated with platelet count (p < 0.001) and the plasma level of IL-6 (p < 0.001) in women (R² = 0.159, p < 0.001). Quartile range of plasma level of IL-6 was associated with plasma level of PDMP after adjustment for diastolic blood pressure, platelet count, and high sensitivity C-reactive protein in men (p < 0.001) and associated with plasma level of PDMP after adjustment for platelet count in women (p < 0.001).

Conclusions

These results suggest the plasma IL-6 is correlated and associated with the plasma PDMPs, markers of activated platelets in healthy individuals.     

Complete mapping of glomeruli based on sensory nerve branching pattern in the primary olfactory center of the cockroach Periplaneta americana

Glomeruli are structural and functional units in the primary olfactory center in vertebrates and insects. In the cockroach Periplaneta americana, axons of different types of sensory neurons housed in sensilla on antennae form dorsal and ventral antennal nerves and then project to a number of glomeruli. In this study, we identified all antennal lobe (AL) glomeruli based on detailed innervation patterns of sensory tracts in addition to the shape, size, and locations in the cockroach. The number of glomeruli is ∼205, and no sex‐specific difference is observed. Anterograde dye injections into the antennal nerves revealed that axons supplying the AL are divided into 10 sensory tracts (T1–T10). Each of T1–T3 innervates small, oval glomeruli in the anteroventral region of the AL, with sensory afferents invading each glomerulus from multiple directions, whereas each of T4–T10 innervates large glomeruli with various shapes in the posterodorsal region, with a bundle of sensory afferents invading each glomerulus from one direction. The topographic branching patterns of all these tracts are conserved among individuals. Sensory afferents in a sub‐tract of T10 had axon terminals in the dorsal margin of the AL and the protocerebrum, where they form numerous small glomerular structures. Sensory nerve branching pattern should reflect developmental processes to determine spatial arrangement of glomeruli, and thus the complete map of glomeruli based on sensory nerve branching pattern should provide a basis for studying the functional significance of spatial arrangement of glomeruli and its developmental basis. J. Comp. Neurol. 518:3907–3930, 2010. © 2010 Wiley‐Liss, Inc.     

Torsades de Pointes induced by a combination of garenoxacin and disopyramide and other cytochrome P450, family 3, subfamily A polypeptide-4-influencing drugs during hypokalemia due to licorice

We report an 82-year-old man who developed ventricular tachycardia and Torsades de Pointes (TdP) after oral administration of garenoxacin, a novel quinolone antibiotic agent that differs from the third-generation quinolones, for pneumonia. He had hypokalemia (K 2.3 mmol/L) induced by licorice and also had received disopyramide for arrhythmia, bicalutamide for prostate cancer, and silodosin for prostate hypertrophy. After taking him off all drugs and administering spironolactone supplemented with potassium, his low serum potassium level was ameliorated. Therefore, although garenoxacin reportedly causes fewer adverse reactions for cardiac rhythms than third-generation quinolone antibiotics, one must be cautious of the interference of other drugs during hypokalemia in order to prevent TdP.     

The RASSF3 candidate tumor suppressor induces apoptosis and G1-S cell-cycle arrest via p53

RASSF3 is the smallest member of the RASSF family of proteins that function as tumor suppressors. Unlike other members of this important family, the mechanisms through which RASSF3 suppresses tumor formation remain unknown. Here, we show that RASSF3 expression induces p53-dependent apoptosis and its depletion attenuates DNA damage-induced apoptosis. We found that RASSF3-induced apoptosis depended upon p53 expression. Exogenous expression of RASSF3 induced G(1)-S arrest, which was also p53 dependent. In contrast, loss of RASSF3 promoted cell-cycle progression, abrogated UVB- and VP-16-induced G(1)-S arrest, decreased p53 protein and target gene expression, and prevented DNA repair. RASSF3 was shown to directly interact with and facilitate the ubiquitination of MDM2, the E3 ligase that targets p53 for degradation, thereby increasing p53 stabilization. Together, our findings show the tumor suppressor activity of RASSF3, which occurs through p53 stabilization and regulation of apoptosis and the cell cycle.     

A case of breast adenocarcinoma changed to squamous cell carcinoma after neoadjuvant chemotherapy

Squamous cell carcinoma(SCC)of the breast is a rare pathological-type cancer with an unclear origin. It has been suggested that breast SCC may originate from squamous metaplasia of the ductal epithelium. We report a case of SCC of the breast which histological carcinoma type changed after neoadjuvant chemotherapy. A 66-year-old woman visited our hospital for a tumor of the left breast. Mammography indicated breast cancer. On CT scan the tumor was 40mm in diameter, and was located in the upper lateral quadrant of the left breast. Because she requested breast-conserving surgery, core needle biopsy(CNB)was performed. The histological findings showed solid-tubular adenocarcinoma, PgR(-), ER(-), HER2(-), cT2cN1cM0, cStage II B. She received neoadjuvant chemotherapy consisting of 4 courses of CEF(cyclophosphamide, epirubicin, 5-fluorouracil)and 3 courses of paclitaxel. After chemotherapy, she was considered to have progressive disease, and a modified radical mastectomy was performed. The resected tumor was cystic and 60mm in diameter, containing muddy fluid. Histopathological examination showed pure squamous cell carcinoma, PgR(-), ER(-), HER2(-), pT3pN0pM0, pStage II B. The cancer metastasized with the light axillary lymph nodes at the 6th month after the operation, and she underwent chemo-radiation therapy. She died 6 years after the operation from brain metastasis.     

Significance of IDH mutations varies with tumor histology, grade, and genetics in Japanese glioma patients

Mutations in isocitrate dehydrogenase 1 (IDH1) and IDH2 are found frequently in malignant gliomas and are likely involved in early gliomagenesis. To understand the prevalence of these mutations and their relationship to other genetic alterations and impact on prognosis for Japanese glioma patients, we analyzed 250 glioma cases. Mutations of IDH1 and IDH2 were found in 73 (29%) and 2 (1%) cases, respectively. All detected mutations were heterozygous, and most mutations were an Arg132His (G395A) substitution. IDH mutations were frequent in oligodendroglial tumors (37/52, 71%) and diffuse astrocytomas (17/29, 59%), and were less frequent in anaplastic astrocytomas (8/29, 28%) and glioblastomas (13/125, 10%). The pilocytic astrocytomas and gangliogliomas did not have either mutation. Notably, 28 of 30 oligodendroglial tumors harboring the 1p/19q co-deletion also had an IDH mutation, and these alterations were significantly correlated (P < 0.001). The association between TP53 and IDH mutation was significant in diffuse astrocytomas (P = 0.0018). MGMT promoter methylation was significantly associated with IDH mutation in grade 2 (P < 0.001) and grade 3 (P = 0.02) gliomas. IDH mutation and 1p/19q co-deletion were independent favorable prognostic factors for patients with grade 3 gliomas. For patients with grade 3 gliomas and without 1p/19q co-deletion, IDH mutation was strongly associated with increased progression-free survival (P < 0.0001) and overall survival (P < 0.0001), but no such marked correlation was observed with grade 2 gliomas or glioblastomas. Therefore, IDH mutation would be most useful when assessing prognosis of patients with grade 3 glioma with intact 1p/19q; anaplastic astrocytomas account for most of these grade 3 gliomas.     

A randomized phase-II trial comparing sequential and concurrent paclitaxel with oral or parenteral fluorinated pyrimidines for advanced or metastatic gastric cancer

Background

The purpose of this study was twofold: (1) to compare S-1 with infusional 5-fluorouracil (FU) to determine which would be a better partner of paclitaxel (PTX), and (2) to compare a concurrent strategy with a sequential one, the latter strategy being the one that is widely used in Japanese general practice.

Methods

The 161 eligible patients were randomized into four arms to receive the following regimens: A (sequential), intravenous 5-FU at 800?mg/m² for 5?days every 4?weeks followed by weekly PTX at 80?mg/m²; B (sequential), S-1 at 80?mg/m² for 4?weeks and 2-week rest followed by PTX; C (concurrent), intravenous 5-FU at 600?mg/m² for 5?days and weekly PTX at 80?mg/m² every 4?weeks; and D (concurrent), S-1 for 14?days and PTX at 50?mg/m² on days 1 and 8 every 3?weeks. The primary endpoint was the overall survival (OS) rate at 10?months.

Results

The ten-month OS rates in arms A, B, C, and D were 63, 65, 61, and 73%, respectively. The OS was best in the concurrent S-1/PTX arm, with a mean survival time of 15.4?months, but no significant difference was observed between the four arms. Response rates were higher in the concurrent arms than in the sequential arms.

Conclusion

Our study did not show sufficient prolongation of survival with the concurrent strategy to proceed to a phase-III trial; however, the sequential arms showed survival comparable to that in the concurrent arms, with less toxicity. In patients who are ineligible for cisplatin (CDDP), sequential treatment starting with S-1 and proceeding to PTX would be a good alternative strategy, considering quality of life (QOL) and the cost-benefits of an oral agent as first-line treatment.