The objective of our study was to examine delays between onset of symptoms and treatment for malignant spinal cord compression （MSCC） and to investigate outcomes of neurological function. We performed a retrospective study of clinical records for 25 patients who had been diagnosed with MSCC at a regional center hospital. Thirteen patients had a history of malignancy at the onset of MSCC and 12 patients had no history. For most patients, pain was the first symptom of MSCC. Pain preceded neurologic symptoms by approximately 2 months. The median delays from onset of symptoms of MSCC to treatment were 49 days for all patients, 79 days for those without a history of malignancy and 41.5 days for those with a history of malignancy. It took 39 days from onset to consultation at the hospital, 7 days from consultation to diagnosis and 11 days from diagnosis to treatment. Neurological status was not exacerbated in 8 of 9 patients who had no other neurologic dysfunction at the time of treatment, while only 4 of 10 patients who had deterioration of motor or sensory function at the time of treatment showed improvement in neurological status. In conclusion, there were many delays in all processes from onset to treatment for MSCC and these delays resulted in poor outcome of neurological function.

AIMChromosome 13 is one of the most frequently altered chromosomes in prostate cancer. The present study was undertaken to examine the role of human chromosome 13 in the progression of prostate cancer.

METHODSHuman chromosome 13 was introduced into highly metastatic rat prostate cancer cells via microcell-mediated chromosome transfer.

RESULTSMicrocell hybrid clones containing human chromosome 13 showed suppression of metastasis to the lung without any suppression of tumorigenicity, except for one clone, which contained the smallest sized human chromosome 13 and did not show any suppression on lung metastasis. Expression of two known tumor suppressor genes, BRCA2 and RB1, which map to chromosome 13, was examined by reverse transcription- polymerase chain reaction analysis. BRCA2 was expressed only in the metastasis-suppressed microcell-hybrid clones, whereas RB1 was expressed in all clones.

CONCLUSIONHuman chromosome 13 contains metastasis suppressor gene(s) for prostate cancer derived from rat. Furthermore, the RB1 gene is unlikely to be involved in the suppression of metastasis evident in this system.

Animals ; Animals, Genetically Modified ; Cell Division ; genetics ; Chromosome Aberrations ; Chromosome Mapping ; Chromosomes, Human, Pair 13 ; Disease Progression ; Genetic Markers ; Humans ; In Situ Hybridization, Fluorescence ; Kinetics ; Male ; Neoplasm Metastasis ; Prostatic Neoplasms ; genetics ; pathology ; prevention & control ; Rats ; genetics

PURPOSE: Single-agent interferon (IFN) is no longer regarded as a standard option for first-line systemic treatment of metastatic renal cell carcinoma (RCC) in Western countries. However, some patients with favorable-risk RCC may still achieve complete and long-lasting remission in response to IFN treatment. The present study compared favorable-risk Japanese patients with metastatic RCC Japanese patients who had been treated with IFN or tyrosine kinase inhibitor (TKI) therapy as a first-line systemic therapy. MATERIALS AND METHODS: From 1995 to 2014, a total of 48 patients with favorable risk as defined by the Memorial Sloan Kettering Cancer Center criteria who did not receive adjuvant systemic therapy were retrospectively enrolled in this study. We assessed the tumor response rate, progression-free survival (PFS), and overall survival (OS). RESULTS: The objective response rate for first-line therapy was 29% in the IFN group and 47% in the TKI group, but this difference did not reach the level of statistical significance. Median OS for IFN and TKI was 71 and 47 months, respectively (p=0.014). Median first-line PFS for IFN and TKI was 20 and 16 months, respectively (no significant difference). First-line IFN therapy did not prove inferior to TKI therapy in terms of OS according to metastatic sites. CONCLUSIONS: IFN is associated with a survival benefit in Japanese patients with favorable-risk metastatic RCC in the era of targeted therapy. Further prospective study is needed.
Adult ; Aged ; Antineoplastic Agents/*therapeutic use ; Carcinoma, Renal Cell/*drug therapy ; Disease-Free Survival ; Female ; Humans ; Interferons/*therapeutic use ; Japan ; Kidney Neoplasms/*drug therapy ; Male ; Middle Aged ; Neoplasm Metastasis/drug therapy ; Protein Kinase Inhibitors/therapeutic use ; Protein-Tyrosine Kinases/antagonists & inhibitors ; Retrospective Studies ; Risk Factors ; Treatment Outcome

AIMThe metastatic ability of a Dunning R-3327 rat prostate cancer subline (AT6.3) was suppressed by the introduction of human chromosome 10, when these hybrid cancer cells were injected subcutaneously into nude mice (Nihei et al., Genes Chromosomes Cancer 14:112-119, 1995). The present study was undertaken to clarify which step of metastasis was suppressed in the human chromosome 10-containing microcell hybrids (AT 6.3-10 clones).

METHODSGelatin zymography, an in vitro invasion assay using a Boyden chamber and an intravenous metastasis assay involving the injection of hybrid cells into nude mice were performed.

RESULTSGelatin zymography revealed that AT6.3-10 microcell hybrid clones expressed the 72 kD type IV collagenase (MMP-2) at an almost equal level as control microcell hybrid clones. Both the invasiveness as measured by the invasion assay and the number of lung metastases as measured by the intravenous metastasis assay of AT6.3-10 hybrid clones were significantly less than those of the AT6.3 parental clone.

CONCLUSIONThe human chromosome 10 suppresses both the local invasion and the metastatic process after entry into the blood circulation of rat prostate cancer. This decrease in local-invasive ability does not seem to require a decrease in MMP-2 activity.

Animals ; Animals, Genetically Modified ; Cell Division ; Chromosomes, Human, Pair 10 ; Gelatin ; analysis ; Humans ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Invasiveness ; Neoplasm Metastasis ; genetics ; Prostatic Neoplasms ; genetics ; pathology ; Rats ; Skin Neoplasms ; genetics ; pathology ; secondary ; Tumor Cells, Cultured

AIMTo evaluate the occurrence and prevalence of microdeletions in the gamma chromosome of patients with azoospermia.

METHODSDNA from 29 men with idiopathic azoospermia was screened by polymerase chain reaction (PCR) analysis with a set of gamma chromosome specific sequence-tagged sites (STSs) to determine microdeletions in the gamma chromosome.

RESULTSDeletions in the DAZ (deleted in azoospermia) loci sgamma254 and sgamma255 were found in three patients with idiopathic azoospermia, resulting in an estimated frequency of deletions of 10.7% in idiopathic azoospermia men.

CONCLUSIONWe conclude that PCR analysis is useful for the diagnosis of microdeletions in the Y chromosome, which is important when deciding the suitability of a patient for assisted reproductive technology such as testicular sperm extracion-intracytoplasmic sperm injection (TESE-ICSI).

Adult ; Base Sequence ; Chromosomes, Human, Y ; DNA Primers ; Euchromatin ; genetics ; Follicle Stimulating Hormone ; blood ; Heterochromatin ; genetics ; Humans ; Luteinizing Hormone ; blood ; Male ; Oligospermia ; blood ; etiology ; genetics ; Polymerase Chain Reaction ; Prolactin ; blood ; Sequence Deletion ; genetics ; Sequence Tagged Sites ; Testosterone ; blood

Androgens play a central role in prostate cancer pathogenesis, and hence most of the patients respond to androgen deprivation therapies. However, patients tend to relapse with aggressive prostate cancer, which has been termed as hormone refractory. To identify the proteins that mediate progression to the hormone-refractory state, we used protein-chip technology for mass profiling of patients' sera. This study included 16 patients with metastatic hormone-refractory prostate cancer who were initially treated with androgen deprivation therapy. Serum samples were collected from each patient at five time points: point A, pre-treatment; point B, at the nadir of the prostate-specific antigen (PSA) level; point C, PSA failure; point D, the early hormone-refractory phase; and point E, the late hormone-refractory phase. Using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry, we performed protein mass profiling of the patients' sera and identified a 6 640-Da peak that increased with disease progression. Target proteins were partially purified, and by amino acid sequencing the peak was identified as a fragment of apolipoprotein C-I (ApoC-I). Serum ApoC-I protein levels increased with disease progression. On immunohistochemical analysis, the ApoC-I protein was found localized to the cytoplasm of the hormone-refractory cancer cells. In this study, we showed an increase in serum ApoC-I protein levels in prostate cancer patients during their progression to the hormone-refractory state, which suggests that ApoC-I protein is related to progression of prostate cancer. However, as the exact role of ApoC-I in prostate cancer pathogenesis is unclear, further research is required.
Aged ; Amino Acid Sequence ; Antineoplastic Agents, Hormonal ; therapeutic use ; Apolipoprotein C-I ; analysis ; blood ; isolation & purification ; Blotting, Western ; Cell Line ; Disease Progression ; Drug Resistance, Neoplasm ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Molecular Sequence Data ; Prognosis ; Prostatic Neoplasms ; drug therapy ; metabolism ; Protein Array Analysis ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

The prognostic significance of initial prostate-specific antigen (PSA) level for metastatic prostate cancer remains uncertain. We investigated the differences in prognosis and response to hormonal therapies of metastatic prostate cancer patients according to initial PSA levels. We analyzed 184 patients diagnosed with metastatic prostate cancer and divided them into three PSA level groups as follows: low (<100 ng ml^-1), intermediate (100-999 ng ml^-1), and high (≥1000 ng ml^-1). All patients received androgen deprivation therapy (ADT) immediately. We investigated PSA progression-free survival (PFS) for first-line ADT and overall survival (OS) within each of the three groups. Furthermore, we analyzed response to antiandrogen withdrawal (AW) and alternative antiandrogen (AA) therapies after development of castration-resistant prostate cancer (CRPC). No significant differences in OS were observed among the three groups (P = 0.654). Patients with high PSA levels had significantly short PFS for first-line ADT (P = 0.037). Conversely, patients in the high PSA level group had significantly longer PFS when treated with AW than those in the low PSA level group (P = 0.047). Furthermore, patients with high PSA levels had significantly longer PFS when provided with AA therapy (P = 0.049). PSA responders to AW and AA therapies had significantly longer survival after CRPC development than nonresponders (P = 0.011 and P < 0.001, respectively). Thus, extremely high PSA level predicted favorable response to vintage sequential ADT and AW. The current data suggest a novel aspect of extremely high PSA value as a favorable prognostic marker after development of CRPC.
Aged ; Aged, 80 and over ; Androgen Antagonists/therapeutic use* ; Disease Progression ; Humans ; Male ; Middle Aged ; Prognosis ; Progression-Free Survival ; Prostate-Specific Antigen/blood* ; Prostatic Neoplasms/mortality* ; Treatment Outcome