Clinical significance of serum autoantibodies against Ras-like GTPases,RalA, in patients with esophageal squamous cell carcinoma

Background

The Ras-like GTPases, RalA and RalB are members of the Ras superfamily of small GTPases. Aberrant activation of Ral is a major cause of human tumorigenesis induced by oncogenic Ras. Serum anti-RalA antibodies are induced in esophageal carcinoma patients. However, detailed comparisons of their pathological characteristics are unavailable, and conventional serum markers have not been well evaluated.

Methods

Serum samples of 171 patients with esophageal squamous cell carcinoma and 73 healthy individuals were analyzed using specifically developed ELISA system for serum anti-RalA antibodies. A cut-off optical density value was fixed at 0.255 (the control mean + 2 SD). Clinicopathological characteristics and positive rates of conventional tumor markers were evaluated for seropositive patients.

Results

Overall positive rate for serum anti-RalA antibodies was 18 %, which gradually increased with the tumor stages. Although the positive rate for serum anti-RalA antibodies was comparable with that of carcinoembryonic antigen (24 %) and CYFRA21-1 (21 %), it was lower than the rate for serum p53 antibodies (31 %) and squamous cell carcinoma antigen (37 %). Although serum anti-RalA antibodies were not associated with other serum markers, it was inversely associated with serum p53 antibodies. No clear association was observed between serum anti-RalA antibodies and RalA immunoreactivity.

Conclusions

Presence of serum anti-RalA antibodies is associated with tumor stages, but not with conventional tumor markers. Serum anti-RalA antibodies may be candidate serum markers in combination with other serum markers for esophageal squamous cell carcinoma.

     

Enteroscopy

Wireless capsule endoscopy and double-balloon endoscopy are new methods of enteroscopy that have been introduced in recent years. Wireless capsule endoscopy is an epoch-making examination method that makes possible an endoscopic imaging examination of the entire small intestine without discomfort and without confining patients to a medical facility. Although it is expected to be useful as an initial examination for finding diseases of the small intestine, it cannot be used for biopsy or treatment. One risk associated with the capsule endoscopy technique is entrapment by strictures. Double-balloon endoscopy is based on a new insertion technique in which two balloons, one at the distal end of the endoscope and the other at the distal end of an overtube, are operated in combination, and the endoscope is inserted while simultaneously shortening the intestine. It can be inserted through either the mouth or the anus, allowing the observation of the entire gastrointestinal tract. It features excellent maneuverability even in the distal small intestine, and enables back-and-forth observation, biopsy, and endoscopic treatment at any given site. These two new enteroscopy techniques are expected to lead to innovations in how diseases of the small intestine are approached.     

Radioimmunoassay and immunological properties of eel calcitonin

The immunological properties of eel calcitonin (CT) were studied by checking the cross-reactivities of eel CT or antisera to eel CT to various CT or antisera to these CT. Antisera to eel CT, raised in guinea pig, did not crossreact with either synthetic salmon, porcine or human CT. The antisera to salmon CT weakly crossreacted with eel CT, whereas eel CT did not crossreact with either antisera to porcine or human CT.     

Ticlopidine alone versus ticlopidine plus aspirin for preventing recurrent stroke

OBJECTIVE: To compare the efficacy and safety of two antiplatelet regimens, ticlopidine alone (200 mg daily) and ticlopidine (100 mg daily) plus aspirin (81 mg daily), in patients with ischemic stroke from the Tokai district of Japan. METHODS: A randomized comparative study was performed from April 1992 until December 1995, with follow-up for an average of 1.59 years (maximum: 3 years). Statistical analysis was done on 270 eligible patients (138 treated with ticlopidine alone and 132 treated with ticlopidine plus aspirin). PATIENTS: A total of 276 patients who had cerebral infarction within the previous 1 to 6 months, or one or more transient ischemic attacks within the previous 3 months. RESULTS: The incidence of ischemic and hemorrhagic stroke, myocardial infarction, and other vascular events was 10.1% (n = 14) in the ticlopidine group and 9.8% (n = 13) in the ticlopidine plus aspirin group, showing no significant difference (p = 0.933). There was also no significant difference in the event-free rate between the two groups (p = 0.5003, Kaplan-Meier analysis and log-rank test). Regarding serious adverse reactions, neutropenia occurred in one patient from the ticlopidine group, while gastric ulcer and thrombocytopenia occurred in one patient each from the ticlopidine plus aspirin group. CONCLUSION: We conclude that both antiplatelet regimens are comparable in efficacy and safety for preventing the recurrence of ischemic stroke.     

A primary thymic adenocarcinoma with two components that traced distinct evolutionary trajectories

Even though it is a rare subtype, identifying the genetic features of thymic adenocarcinoma is valuable for a multifaceted understanding of thymic epithelial tumors. We experienced a female patient with thymic adenocarcinoma associated with thymic cysts. The tumor consisted of a solid whitish lesion (lesion-1) and a large cystic lesion with small papillary nodules (lesion-2). Microscopically, lesion-1 exhibited poorly differentiated adenocarcinoma accompanying numerous inflammatory cell infiltrates, and lesion-2 (the nodules within the cystic lesion) exhibited enteric-type adenocarcinoma. Consistent with the histological difference, whole-exome sequencing revealed that these two components exhibited distinct genetic features, except for only a few shared mutations, including CDKN2A truncation. Lesion-1 exhibited microsatellite instability-high signature with high mutation burden, for which immune checkpoint inhibitors might apply; and lesion-2 exhibited whole-genome doubling with KRAS hotspot mutation. Our case presents novel genetic features of thymic adenocarcinoma and demonstrates that distinct mutational processes can be operative within a single tumor.