Histone H2A T120 Phosphorylation Promotes Oncogenic Transformation via Upregulation of Cyclin D1.

How deregulation of chromatin modifiers causes malignancies is of general interest. Here, we show that histone H2A T120 is phosphorylated in human cancer cell lines and demonstrate that this phosphorylation is catalyzed by hVRK1. Cyclin D1 was one of ten genes downregulated upon VRK1 knockdown in two different cell lines and showed loss of H2A T120 phosphorylation and increased H2A K119 ubiquitylation of its promoter region, resulting in impaired cell growth. In vitro, H2A T120 phosphorylation and H2A K119 ubiquitylation are mutually inhibitory, suggesting that histone phosphorylation indirectly activates chromatin. Furthermore, expression of a phosphomimetic H2A T120D increased H3 K4 methylation. Finally, both VRK1 and the H2A T120D mutant histone transformed NIH/3T3 cells. These results suggest that histone H2A T120 phosphorylation by hVRK1 causes inappropriate gene expression, including upregulated cyclin D1, which promotes oncogenic transformation.

Aqueous Synthesis of Manganese Phosphate Hydrate Crystals for Creating Inorganic Pigment Materials.

Manganese phosphate hydrate crystals were prepared from aqueous solutions containing MnCl2, (NH4)2HPO4, and citric acid. Switzerite [Mn3(PO4)2·7H2O] and niahite (NH4MnPO4·H2O) phases were produced at room temperature, and then, hureaulite [Mn5(PO3OH)2(PO4)2·4H2O] particles were obtained by aging at 80 °C or by hydrothermal treatment at 100-180 °C. The lower aging temperature (80 °C) and the chelation of Mn2+ ions by citric acid provided a slower crystal growth, resulting in large hexagonal prism blocks of ca. 500 µm in size. These were found to be single crystals of hureaulite by powder and single-crystal X-ray diffraction analysis. Diffuse reflectance spectroscopy and evaluation using L*a*b* color parameters indicated that the large single crystals present a vivid pink color and high transparency.

Spinal fractures in patients with diffuse idiopathic skeletal hyperostosis: Clinical characteristics by fracture level.

BACKGROUND: Diffuse idiopathic skeletal hyperostosis (DISH) makes the spine prone to unstable fractures with neurological deterioration. This study was conducted to assess clinical and radiographic features of spinal fractures in DISH by the level of spinal injury, and to evaluate the optimal treatment for each level. METHODS: A multicenter retrospective study over a 5-year period, including 46 patients (35 males; 11 females) with a mean age of 77.2 ± 9.7 years at the time of injury. By fracture level, there were 7 cervical (15.2%), 25 thoracic (54.3%), and 14 lumbar (30.4%) fractures. We recorded the cause of injury, whether diagnosis was delayed, and neurological status by Frankel grade. Ossification and fracture patterns were assessed by CT-multi-planar reconstruction (MPR). RESULTS: Neurological status immediately after the cervical-spine injury was C (28.6%) or E (71.4%); after thoracic injury, C (12.0%) or E (88.0%); and after lumbar injury, D (21.4%) or E (78.6%). Inability to walk at admission was more frequent in patients with a spinal-cord injury above the lumbar level (P = .033). Vertebral-body fractures were observed in 14.3% of the cervical injuries, 80.0% of the thoracic injuries, and 50.0% of the lumbar injuries (P = .004). Most patients with a cervical fracture had a disc-level fracture (85.7%). Posterior-column ankylosis was observed in 14.3% of the cervical-fracture group, 72.0% of the thoracic-fracture group, and 78.6% of the lumbar-fracture group (P = .008). CONCLUSION: Ossification and fracture patterns in patients with DISH varied distinctly by the level of spinal injury. Intervertebral-disc fractures were frequently observed in the cervical spine. Delayed diagnosis, vertebral-body fracture, and posterior-column ankylosis were observed in the thoracolumbar spine. This study recommends 3 above and 3 below fusion, to avoid instrumentation failure in the fixation of spinal fracture in patients with DISH.

[Euglycemic Diabetic Ketoacidosis Caused by a Sodium-glucose Co-transporter (SGLT) 2 Inhibitor after Coronary Artery Bypass Grafting].

A 65-year-old woman with type Ⅱ diabetes and unstable angina presented with chest pain due to in-stent restenosis. Her regular medication comprised an sodium-glucose co-transporter( SGLT) 2 inhibitor. Because of unstable hemodynamic status, semi-emergency coronary artery bypass grafting (CABG) was performed. Postoperatively, the cardiac and hemodynamic status stabilized, but there was progression of metabolic acidosis. Based on the presence of massive urinary ketone bodies without hyper glycosuria, the patient was diagnosed with euglycemic diabetic ketoacidosis( DKA) caused by an SGLT2 inhibitor. Ketoacidosis without elevated blood glucose( i.e., euglycemic DKA) has been reported to be associated with intake of an SGLT2 inhibitor, which promoted glucose excretion in the urine. Our patient developed euglycemic DKA due to the progression of myocardial ischemia and surgical stress. Guidelines in other countries have stipulated that SGLT2 inhibitor should be stopped 24 hours preoperatively. In our case, euglycemic DKA occurred even when the SGLT2 inhibitor was stopped for more than 24 hours preoperatively. Further studies on the withdrawal of an SGLT2 inhibitor in the appropriate perioperative period are required.

CT-based morphological analysis of spinal fractures in patients with diffuse idiopathic skeletal hyperostosis.

PURPOSE: To clarify correlations between spinal fracture and delayed paralysis in patients with diffuse idiopathic skeletal hyperostosis (DISH) using computed tomography (CT) with multiplanar reformatting (CT-MPR). DISH increases susceptibility to unstable spinal fractures, leading to neurological deterioration. The pathomechanism of the neurological injury is unclear. METHODS: This multicenter retrospective study included 42 DISH patients (32 male; 10 female) treated for 45 spinal fractures during a 5-year period. The mean age at the time of injury was 77.1 ± 10.1 years. The cause of injury, delay in diagnosis, fracture location, and neurological status were recorded, and anterior- and posterior-column fractures, a fracture displacement over 3 mm, and posterior-column ankylosis were assessed using CT-MPR. RESULTS: Most fractures (73.8%) resulted from trivial trauma, such as falling from a standing or sitting position. Diagnosis was delayed in 47.6% of the patients, primarily due to delays in seeking medical attention (65.0%). Although 78.6% of the patients were neurologically intact at the time of injury, 54.8% developed paralysis, defined by a change in one or more Frankel-score levels during short-term follow-up. Of the fractures, 39.1% were in the vertebral body, and 60.9% were at the disc level. Fractures with posterior-column ankylosis were significantly associated with delayed paralysis. CONCLUSIONS: CT-MPR was useful for evaluating spinal fractures and determining treatment in patients with DISH. Fractures associated with posterior-column ankylosis resulted in unstable three-column injuries that led to delayed neurological deterioration. Early surgical stabilization of such fractures is recommended to avoid delayed paralysis.

[Traumatic injury of the proximal aortic arch after blunt chest trauma;report of a case].

We report a rare case of an proximal aortic arch injury caused by blunt chest trauma. A 48-year-old woman was transferred to our hospital because of traffic accident. Computed tomography (CT) showed a small ulcer-like projection (ULP) at the proximal part of the aortic arch. An elective surgery for aortic repair was performed because of significant enlargement of the ULP in the aortic arch revealed by follow-up CT. The patient's postoperative course was uneventful, and she was discharged on the 14th postoperative day.

Effect of renin-angiotensin system inhibitors on cardiovascular events in hemodialysis patients with hyperphosphatemia: A post hoc analysis of the LANDMARK trial.

INTRODUCTION: The clinical benefits of renin-angiotensin system inhibitors (RASi) in patients undergoing hemodialysis remain obscure. METHODS: This is a post hoc cohort analysis of the LANDMARK trial investigate whether RASi use was associated with cardiovascular events (CVEs) and all-cause mortality. A total of 2135 patients at risk for vascular calcification were analyzed using a Cox proportional hazards model with propensity-score matching. RESULTS: The risk of CVEs was similar between participants with RASi use at baseline and those without RASi use at baseline and between participants with RASi use during the study period and those without RASi use during the study period. No clinical benefits of RASi use on all-cause mortality were observed. Serum phosphate levels were significantly associated with the effect of RASi on CVEs. CONCLUSIONS: RASi use was not significantly associated with a lower risk of CVEs or all-cause mortality in hemodialysis patients at risk of vascular calcification.

Effect of aspirin on cardiovascular events in patients undergoing hemodialysis with hyperphosphatemia: A post hoc analysis of the LANDMARK trial.

INTRODUCTION: The clinical benefits of aspirin in patients undergoing hemodialysis remain unclear. METHODS: The secondary analysis of the LANDMARK trial investigated whether aspirin use was associated with cardiovascular events (CVEs) and all-cause mortality was performed. A total of 2135 patients at risk for vascular calcification were analyzed using a Cox proportional hazards model with propensity score matching. RESULTS: The risk of CVEs was comparable between participants with aspirin use at baseline and those without at baseline, between participants with aspirin use during the study period and those without during the study period, and between participants with new aspirin prescription and those without aspirin use during the study period. CONCLUSION: Aspirin use was not significantly associated with a lower risk of CVEs in participants undergoing hemodialysis patients at risk of vascular calcification.

Vepafestinib is a pharmacologically advanced RET-selective inhibitor with high CNS penetration and inhibitory activity against RET solvent front mutations.

RET receptor tyrosine kinase is activated in various cancers (lung, thyroid, colon and pancreatic, among others) through oncogenic fusions or gain-of-function single-nucleotide variants. Small-molecule RET kinase inhibitors became standard-of-care therapy for advanced malignancies driven by RET. The therapeutic benefit of RET inhibitors is limited, however, by acquired mutations in the drug target as well as brain metastasis, presumably due to inadequate brain penetration. Here, we perform preclinical characterization of vepafestinib (TAS0953/HM06), a next-generation RET inhibitor with a unique binding mode. We demonstrate that vepafestinib has best-in-class selectivity against RET, while exerting activity against commonly reported on-target resistance mutations (variants in RETL730, RETV804 and RETG810), and shows superior pharmacokinetic properties in the brain when compared to currently approved RET drugs. We further show that these properties translate into improved tumor control in an intracranial model of RET-driven cancer. Our results underscore the clinical potential of vepafestinib in treating RET-driven cancers.

Lemon Myrtle (Backhousia citriodora) Extract and Its Active Compound, Casuarinin, Activate Skeletal Muscle Satellite Cells In Vitro and In Vivo.

Sarcopenia is an age-related skeletal muscle atrophy. Exercise is effective in improving sarcopenia via two mechanisms: activation of skeletal muscle satellite cells (SCs) and stimulation of muscle protein synthesis. In contrast, most nutritional approaches for improving sarcopenia focus mainly on muscle protein synthesis, and little is known about SC activation. Here, we investigated the effect of lemon myrtle extract (LM) on SC activation both in vitro and in vivo. Primary SCs or myoblast cell lines were treated with LM or its derived compounds, and incorporation of 5-bromo-2'-deoxyuridine, an indicator of cell cycle progression, was detected by immunocytochemistry. We found that LM significantly activated SCs (p < 0.05), but not myoblasts. We also identified casuarinin, an ellagitannin, as the active compound in LM involved in SC activation. The structure−activity relationship analysis showed that rather than the structure of each functional group of casuarinin, its overall structure is crucial for SC activation. Furthermore, SC activation by LM and casuarinin was associated with upregulation of interleukin-6 mRNA expression, which is essential for SC activation and proliferation. Finally, oral administration of LM or casuarinin to rats showed significant activation of SCs in skeletal muscle (p < 0.05), suggesting that LM and casuarinin may serve as novel nutritional interventions for improving sarcopenia through activating SCs.

Stent failure in the management of malignant extrinsic ureteral obstruction: risk factors.

There is still controversy surrounding the indications for performing either a retrograde ureteral stent or percutaneous nephrostomy to manage malignant extrinsic ureteral obstruction (MEUO). We retrospectively analyzed 53 patients who underwent a decompression of MEUO using retrograde ureteral stent. Ureteral stent failure occurred in 18 of 53 patients (34%). Multivariate analysis showed that gastrointestinal cancer as the primary disease, poor preoperative performance status and severe preoperative hydronephrosis were independent predictors of stent failure. Based on the present data, we propose an algorithm for the management of MEUO.

Chiral phosphoric acid catalyzed transfer hydrogenation: facile synthetic access to highly optically active trifluoromethylated amines.

Amines to an end: highly optically active α-CF(3)-functionalized amines can be obtained using metal-free reaction conditions. The method involves the transfer hydrogenation of CF(3)-substituted ketimines catalyzed by 1 and reductive amination of CF(3)-substituted ketones. The synthetic utility of this method was demonstrated by the synthesis of a CF(3) analogue of NPS R-568. PMP=para-methoxyphenyl.

Risk factors for lymph node metastasis from gastric cancers with submucosal invasion.

BACKGROUND: Accurate prediction of the metastatic status of lymph nodes (LNs) is clinically important for selecting treatment strategies in patients with gastric cancer with submucosal invasion (GCSM). In this study, we determined the risk factors for lymph node metastasis (LNM), including micrometastasis, in patients with GCSM. MATERIALS AND METHODS: A total of 5610 LNs dissected from 189 patients with GCSM who had undergone a standard gastrectomy were immunostained with CAM 5.2 monoclonal antibody to detect LN micrometastasis. Clinicopathological risk factors for lymph node metastasis (LNM), including micrometastasis, were determined. RESULTS: LNM was detected in 216 LNs (107 macroscopic metastases, 72 micrometastases, and 37 isolated tumor cells) in 55 (29.1%) of the 189 patients with GCSM. A multivariate analysis revealed that a tumor size of more than 20 mm, a mixed- or undifferentiated-type histology, a vertical tumor invasion depth in the submucosal layer (VTIDSM) of more than 0.5 mm, and the presence of lymphatic vessel invasion (LVI) were independent risk factors for LNM. The incidences of LNM in patients with 0, 1, 2, 3, and 4 risk factors were 0, 4.5, 11.4, 36.1, and 52.9%, respectively. Among the patients with only 1 or 2 risk factors, all the metastatic lesions were located only in the first tier. On the other hand, LNM in the second tier was also detected in 24.5% of the patients with more than 3 risk factors. CONCLUSIONS: Tumor size, histologic type, VTIDSM, and LVI are important risk factors for predicting the presence and extent of LNM in patients with GCSM.

Sentinel node mapping guided by indocyanine green fluorescence imaging during laparoscopic surgery in gastric cancer.

BACKGROUND: Indocyanine green (ICG) fluorescence imaging has recently been reported as a new method for sentinel node (SN) mapping in several types of cancers. In this study, we determined the possible usefulness of SN mapping guided by ICG fluorescence imaging during laparoscopy-assisted gastrectomy (LAG) for gastric cancer. METHODS: Our series consisted of 77 patients with cT1- or cT2-stage gastric cancer who had undergone LAG (LAG group; 38 patients) or conventional open gastrectomy (OG group; 39 patients). Intraoperative SN mapping guided by ICG fluorescence imaging was conducted with a charge-coupled device camera with a light-emitting diode as the light source and a cut filter as the detector. RESULTS: The detection rate and mean number of fluorescent nodes (FNs) were 94.7% and 7.9, respectively, in the LAG group, and 94.9% and 7.2, respectively, in the OG group. The accuracy and false-negative rates were 97.2% (35 of 36 cases) and 25% (1 of 4), respectively, in the LAG group, and 91.9% (34 of 37) and 23.1% (3 of 13), respectively, in the OG group. Among 33 LAG group patients and 27 OG group patients without FN metastasis, lymph node metastasis was found only in non-SNs located in the same lymphatic basin as the detected FNs. CONCLUSIONS: SN mapping guidance by ICG fluorescence imaging could be useful for predicting the lymph node metastasis in gastric cancer, even during LAG. Our data suggest that dissection of the lymphatic basin containing FNs with laparoscopic surgery may be a promising approach as a new type of minimally invasive surgery for patients with cT1- or cT2-stage gastric cancer having no metastasis in FNs.

Strings of metal half-shells fabricated using colloidal particle monolayer as a template.

A two-dimensional (2-D) polystyrene (PS) particle monolayer is demonstrated as a template for the fabrication of one-dimensional (1-D) strings of metal shells. Metal is deposited by vacuum evaporation onto the PS particle monolayer, which is tilted at an angle (theta) between the normal of the monolayer plane and the direction of metal deposition. The effects of the metal deposition thickness, the tilt angle (theta) of the particle monolayer, and the type of metal on the formation of 1-D strings of metal shells are investigated. Strings of fan-shaped Au shells are obtained at a given tilt angle and deposition thickness. On the other hand, 1-D strings of Cr and Ag cannot be obtained, and they tend to form 2-D films and half-shell dots of the metal, respectively.

Sentinel node mapping guided by indocyanine green fluorescence imaging in gastric cancer.

OBJECTIVE: In this study, we determined the possible usefulness of sentinel node (SN) mapping guided by indocyanine green (ICG) fluorescence imaging in the management of gastric cancer. SUMMARY BACKGROUND DATA: ICG fluorescence imaging system has recently been developed for obtaining biochemical information from living tissues. METHODS: Our series consisted of 56 patients with gastric cancer who underwent standard gastrectomy with lymphadenectomy. Two milliliters of ICG solution (0.5%) was injected into the submucosa around the tumor endoscopically before the operation or into the subserosa intraoperatively. ICG fluorescence imaging was conducted using a charge-coupled device camera with a light-emitting diode having a wavelength of 760 nm as the light source and a cut filter to filter out light with wavelengths below 820 nm as the detector. RESULTS: SNs were detected in 54 (96.4%) of the 56 patients, and the mean number of SNs was 7.2 +/- 7.0. Even SNs that were not green in color could be easily and clearly visualized by ICG fluorescence imaging. cT1-stage cancers were associated with a significantly higher accuracy rate (97.2% vs. 72.2%, P = 0.0127) than cT2-or cT3-stage cancers. Preoperative ICG injection was associated with a significantly higher incidence of cT1-stage cancers (87.1% vs. 40.0%, P = 0.0004), a larger mean number of SNs (9.9 +/- 7.5 vs. 4.1 +/- 5.0, P < 0.0001), a higher accuracy rate (100% vs. 73.9%, P = 0.0039), and a lower false negative rate (0% vs. 60.0%, P = 0.0345) as compared with intraoperative ICG injection. CONCLUSIONS: This study shows that ICG fluorescence imaging allows highly sensitive image-guided intraoperative SN mapping in cases of gastric cancer. Our data suggest that SN mapping guided by ICG fluorescence imaging might be useful for predicting the metastatic status in lymph nodes in cases of gastric cancer, especially those with cT1-stage cancer.

Radical prostatectomy for high-risk prostate cancer: biochemical outcome.

OBJECTIVES: To determine the biochemical outcome following radical prostatectomy alone in patients with high-risk prostate cancer. METHODS: Between January 2002 and August 2007, 252 patients underwent radical retropubic prostatectomy. Those who received neoadjuvant hormone therapy were excluded from this analysis. Based on pre-operative data, we stratified the patients into low, intermediate, and high-risk groups according to the risk criteria of the National Comprehensive Cancer Network in 2003, respectively. Prostate-specific antigen (PSA) failure was defined as any detectable PSA level higher than 0.2 ng/mL. RESULTS: The PSA failure-free survival rate for the high-risk group (n = 46) was 64.5% after a median follow-up period of 39 months. Among patients with high-risk disease, none with pathologically organ-confined cancer (n = 19) and a negative surgical margin had PSA failure. The PSA failure-free rate in patients with non organ-confined cancer (n = 27) was 39.5%. Among the pretreatment variables, a positive biopsy core percentage (the number of positive biopsy cores/total biopsy core) >or=30 was a significant independent predictor of extra prostatic extension. CONCLUSIONS: Radical prostatectomy is feasible in high-risk prostate cancer patients, only if they have a pathologically organ-confined disease.

TAS-121, A Selective Mutant EGFR Inhibitor, Shows Activity Against Tumors Expressing Various EGFR Mutations Including T790M and Uncommon Mutations G719X.

TAS-121 is a novel orally active selective covalent inhibitor of the mutant EGFR. We performed preclinical characterization of TAS-121 and compared its efficacy and selectivity for common EGFR mutations (Ex19del and L858R), first- and second- generation EGFR-tyrosine kinase inhibitor (EGFR-TKI) resistance mutation (T790M), and uncommon mutations (G719X and L861Q) with those of other EGFR-TKIs. We also commenced investigation of the clinical benefits of TAS-121. The IC50 for intracellular EGFR phosphorylation was determined by using Jump-In GripTite HEK293 cells transiently transfected with EGFR expression vectors. Mouse xenograft models were used to evaluate the antitumor activity of TAS-121. TAS-121 potently inhibited common activating and resistance EGFR mutations to the same extent as another third-generation EGFR-TKI (osimertinib). In addition, TAS-121 showed equivalent inhibitory activity against some uncommon mutations such as G719X and L861Q. Furthermore, TAS-121 demonstrated greater selectivity for mutant EGFRs versus the wild-type EGFR compared with other EGFR-TKIs. Moreover, TAS-121 displayed antitumor activity in SW48 (EGFR G719S) and NCI-H1975 (EGFR L858R/T790M) xenograft models, and achieved an objective response in patients with NSCLC with EGFR mutations including G719A mutation. In conclusion, TAS-121 is a novel third-generation EGFR-TKI and demonstrates antitumor activities in patients with NSCLC expressing either common or uncommon EGFR mutations.

Spinal fractures in diffuse idiopathic skeletal hyperostosis: Advantages of percutaneous pedicle screw fixation.

PURPOSE: To validate the effectiveness of percutaneous pedicle screw (PPS) fixation for spinal fractures associated with diffuse idiopathic skeletal hyperostosis (DISH) by comparing surgical outcomes for PPS fixation and conventional open posterior fixation. Patients with DISH are vulnerable to unstable spinal fractures caused by trivial trauma, and these fractures have high rates of delayed paralysis, postoperative complications, and mortality. METHODS: This retrospective study assessed surgical outcomes for 16 patients with DISH (12 men; mean age 76.1 ± 9.4 years) who underwent PPS fixation for spinal fractures (pedicle screw (PS) group), and for a control group of 25 patients with DISH (18 men; mean age 77.9 ± 9.9 years) who underwent conventional open fixation (O group) at our affiliated hospitals from 2007 to 2017. We evaluated the preoperative physical condition (American Society of Anesthesiologists (ASA) classification), neurological status (Frankel grade), and improvement after surgery, fusion length, operating time, estimated blood loss, and perioperative complications. RESULTS: Preoperatively, the PS group consisted of one ASA-1 patient, eight ASA-2 patients, six ASA-3 patients, and one ASA-4 patient; by Frankel grade, there were 2 grade B patients, 13 grade C, 4 grade D, and 6 grade E patients. The O group had 2 ASA-1 patients, 13 ASA-2, 9 ASA-3, and 1 ASA-4 patients. Frankel grades in the O group reflected severe neurological deficits, with 3 grade C patients, 2 grade D, and 11 grade E ( p = 0.032) patients. The two groups had similar rates of neurological improvement (33.3% of PS and 40.0% of O patients; p = 0.410) and mean fusion length (PS 5.1 ± 0.8 segments; O 4.9 ± 1.2). The mean operating time and estimated blood loss were 168.1 ± 46.7 min and 133.9 ± 116.5 g, respectively, in the PS group, and 224.6 ± 49.8 min and 499.9 ± 368.5 g in the O group. Three O-group patients died of hypovolemic shock, respiratory failure, and pneumonia, respectively, within a year of surgery. CONCLUSION: Conventional open posterior fixation and PPS fixation for DISH-related spinal fractures were similar in fusion length and neurological improvement. However, PPS fixation was less invasive and had lower complication rates.

Haptoglobin-beta chain defined by monoclonal antibody RM2 as a novel serum marker for prostate cancer.

In our previous study, monoclonal antibody RM2, established toward the glycosyl epitope, reflected grade of malignancy of prostate cancer cells whereas RM2 reactivity to benign glands was negative or weak. RM2 reactivity was also detected in stroma, suggesting the glycoprotein RM2 recognizes could be released into the bloodstream. Then, we explored RM2 reactivity to sera of early prostate cancer. We compared RM2 reactivity to sera between 62 patients with early prostate cancer and 43 subjects with benign prostatic disease, and examined RM2 reactivity before and after radical prostatectomy in 15 patients by Western blotting. We also examined RM2 reactivity to sera of the other urogenital cancers. RM2 reactivity was significantly enhanced on a serum glycoprotein with molecular mass approximately 40 kDa, hereby termed GPX, in the patients with early prostate cancer when compared with those with benign prostatic disease (p < 0.0001). Setting an appropriate cutoff level, RM2 reactivity to GPX for detection of prostate cancer had sensitivity of 87% and specificity of 84%, respectively. Furthermore, the level of RM2 reactivity significantly decreased after radical prostatectomy (p = 0.006). However, increased RM2 reactivity to GPX was also observed in the other urogenital cancers. The proteomics approach identified GPX as haptoglobin-beta chain and RM2 showed preferential reactivity toward haptoglobin-beta chain derived from prostate cancer when compared with polyclonal anti-haptoglobin antibody. Haptoglobin-beta chain defined by RM2 is a novel serum marker that may be useful for detection of early prostate cancer when coupled with prostate-specific antigen because it is not specific to prostate cancer.