A case responding to weekly paclitaxel (TXL) therapy as third line chemotherapy for scirrhous type gastric cancer

A 67-year-old female was admitted to our hospital in May, 2001 for examination. She was diagnosed with advanced gastric cancer that was inoperable due to peritoneal dissemination. Seventeen courses of sequential MTX and 5-FU therapy, and 2 courses of TS-1 plus CDDP were carried out. A partial response (PR) and prolonged NC were obtained after these chemotherapies. However, pleural effusion and ascites appeared again, and we diagnosed progressive disease. As a third line chemotherapy for this patient, paclitaxel (TXL) was administered. Treatment consisted of two 3-week courses of paclitaxel 70 mg per m2 on day 1 of each week, with a 1-week break between the courses. Two weeks after the start of this therapy, pleural effusion and ascites had completely disappeared. Paclitaxel is considered to be promising for advanced gastric cancers, as second or third line chemotherapy with paclitaxel for patients with inoperable gastric cancer seems to be effective in improving QOL.     

A case of advanced gastric cancer which became operable after chemotherapy with combination of TS-1/CDDP and in which complete disappearance of liver metastasis was histopathologically confirmed

We encountered a patient in whom TS-1/cisplatin (CDDP) combination chemotherapy was effective. The cancer became operable, and complete disappearance of liver metastasis was histopathologically confirmed. The patient was a 65-year-old man who presented with complaints of epigastric discomfort and anorexia. Based on upper GI endoscopy and abdominal CT, type 1 gastric cancer associated with liver and abdominal lymph node metastases was diagnosed. The cancer was judged to be inoperable, and chemotherapy with a combination of TS-1 and CDDP was initiated. One course of treatment consisted of administration of 120 mg/day of TS-1 for 21 days followed by 14 days of withdrawal, and administration of 100 mg/body/day of CDDP on day 8 (80 mg/body/day in the second course). After two courses of treatment, the primary lesion and the liver and lymph node metastatic lesions decreased in size (reduction ratios were 42.3%, 90.5% and 85.2%, respectively). The tumor marker values became normal. Subsequently, the cancer was judged to have become operable. After consultation with the patient, total gastrectomy, splenectomy, partial hepatectomy, and D3 dissection were performed, and curability B was achieved. The only adverse event of Grade 2 or more severity observed during drug administration was anorexia. Liver metastasis was judged from pathological findings to have disappeared. The postoperative course was uneventful and the patient was discharged from the hospital. To date, there have been no signs of recurrence. TS-1/CDDP therapy is believed to provide effective treatment against liver metastasis and lymph node metastasis of gastric cancer.     

Cimetidine inhibits the adhesion of cancer cells with sialyl Lewis epitope onto the vascular endothelium

The attachment of circulating cancer cells to vascular endothelium is considered an important initial step in hematogenous metastasis. We believe that hematogenous metastasis can be inhibited by blocking the adhesion of cancer cells to vascular endothelium. We demonstrated that cimetidine suppressed the expression of E-selectin on the surface of HUVECs, which was a ligand to the sialyl Lewis (sLe) epitope. Thereby, adhesion of HT-29 cells to HUVECs was inhibited by cimetidine pretreatment. In this study, adhesion between cancer cells and HUVECs was observed by a high-speed video recording system. We examined whether or not cimetidine inhibited the adhesion of cancer cells with the sLe epitope, such as gastric, esophageal and breast cancers, to HUVECs. Cimetidine was able to block the adhesion of gastric, esophageal and breast cancer cells with the sLe epitope. We conclude that cimetidine would be effective for inhibiting hematogenous metastasis on gastric, esophageal and breast cancer cells with the expression of sLe epitope.     

Long-lasting gene expression by particle-mediated intramuscular transfection modified with bupivacaine: combinatorial gene therapy with IL-12 and IL-18 cDNA against rat sarcoma at a distant site

The immune response is modulated by genetic adjuvants using plasmid vectors expressing cytokines. Skeletal muscle can express a foreign gene intramuscularly administered via a needle injection, and the potential of muscle as a target tissue for somatic gene therapy in treating cancer has been explored. In the present study, we investigated the efficacy of particle-mediated intramuscular transfection modified with a local anesthetic agent, bupivacaine, on luciferase and green fluorescent protein. The results indicate that these proteins are more efficiently expressed and persist longer in muscle modified in this way compared with the needle-injection method. Using an established rat sarcoma model, particle-mediated intramuscular gene-gun therapy with a combination of IL-12 and IL-18 cDNA was conducted. Growth of the distant sarcoma was significantly inhibited by particle-mediated intramuscular combination gene therapy, and the survival rate was also improved. Furthermore, the combination gene-gun therapy maintained significant levels of interferon-gamma and induced a high activity of tumor-specific cytotoxic T lymphocytes. These results suggest that the sustained local delivery of IL-12 and IL-18 cDNA using intramuscular gene-gun therapy modified with bupivacaine can induce long-term antitumor immunity, and can provide the great advantage of inhibiting the disseminated tumor.     

Involvement of NMDA receptors in Zif/268 expression in the trigeminal nucleus caudalis following formalin injection into the rat whisker pad

We investigated the involvement of N-methyl-D-aspartate (NMDA) glutamate receptor in the expression of the proteins Zif/268 and c-Fos elicited by painful stimuli. To this purpose, the effect of the administration of MK-801, an NMDA receptor antagonist, on Zif/268 and c-Fos expression following a noxious stimulus, represented by formalin injection into the whisker pad of rats, was examined in neurons of the trigeminal nucleus caudalis. Furthermore, the co-localization of formalin injection-evoked Zif/268 and c-Fos expression and subunit 1 of the NMDA receptor (NR1) was studied in this nucleus. Zif/268 or c-Fos immunoreactivity elicited by formalin injection was significantly reduced by pretreatment with MK-801 in the superficial layer of the trigeminal nucleus caudalis; more than 40% of the neurons expressing Zif/268 and c-Fos in this layer were also immunolabeled by NR1. On the other hand, there was little effect of MK-801 administration on Zif/268 and c-Fos immunoreactivity in the nucleus proprius and deep lamina V of the trigeminal nucleus caudalis, while most neurons expressing Zif/268 or c-Fos in these two regions were labeled by NR1. These results point out differences between the superficial and deeper layers of the trigeminal nucleus caudalis in the involvement of NMDA receptor in the mechanisms underlying the expression of protein products of immediate early genes induced by painful stimuli.     

Prism adaptation response is useful for predicting surgical outcome in selected types of intermittent exotropia

PURPOSE: To evaluate the prevalence of prism adaptation response in Japanese patients with intermittent exotropia (X [T]) using the prism adaptation test and to assess whether patients with selected types of X [T] benefit from surgical outcome to which prism adaptation response may contribute. METHODS: In a prospective study, 128 consecutive patients with X [T] between 1990 and 1995 were enrolled. The prism adaptation test was conducted by neutralizing the angle of deviation for 2 to 3 hours. Patients who showed an increase in exodeviation by 10triangle up or more with the prism adaptation test were defined as having a prism adaptation response. For classification of the pattern of X [T], we chose a value of 15triangle up as the difference between the distance and near measurements. RESULTS: The percentage of patients in whom the prism adaptation response was observed at near fixation was significantly larger than those at distance fixation [35 (27%) patients versus 10 (8%) patients, P <.05]. Of 35 patients shown to have a prism adaptation response at near fixation, 21 patients (83%) had the basic type of exotropia. Fourteen patients (17%) with the basic type were changed to convergence insufficiency type because of an increase in near deviation and were defined as pseudo basic type. Patients with pseudo basic type had a significantly better surgical outcome compared with that of true basic type, whereas in the convergence insufficiency type, no definite tendency was found between the two subtypes, true and pseudo types. CONCLUSION: Patients with the pseudo basic type of X [T] in whom a prism adaptation response was demonstrated had a more favorable surgical outcome.     

Computed tomography measurement of the surgical and clinical transepicondylar axis of the distal femur in osteoarthritic knees

To assess rotational alignment of the distal femur, 2 types of transepicondylar axes have been used in the literature. We compared surgical and clinical epicondylar axes in the measurement of rotational alignment of the femur in planning for total knee arthroplasty (TKA). We examined 48 patients who were candidates for TKA. Computed tomography images of both knees were obtained, and condylar twist angle and posterior condylar angle were measured. The medial sulcus was detected in only 33 knees. The more severe the grade of osteoarthritis, the more difficult it was to detect the medial sulcus. The most prominent point of medial epicondyle was detectable in all knees. We recommend the use of the clinical epicondylar axis in computed tomography measurement in selective planning for TKA.     

Co-overexpression of p53 protein and epidermal growth factor receptor in human papillary thyroid carcinomas correlated with lymph node metastasis, tumor size and clinicopathologic stage.

Expressions of p53 protein and epidermal growth factor receptor (EGFR) were immunohistochemically investigated in 111 patients with papillary thyroid carcinomas (PTC) in order to evaluate their co-expression in relation to lymph node metastases (LNM), tumor size and clinicopathologic stage. In PTC, positive staining for p53 in dewaxed sections was present in nuclei or cytoplasm, or in both, whereas surface linear or cytoplasmic staining for EGFR was observed with varying degrees of extent and intensity. Positive reaction (more than 10% of tumor cells positive) was observed in 65 cases (58. 5%) for p53, and in 87 cases (78.4%) for EGFR. A significant correlation was found between p53 protein and EGFR overexpressions (p<0.01). Notably, p53-positive cases always exhibited positive staining for EGFR. Forty-four patients (39.6%) exhibited concomitant LNM, most of whom had both p53 and EGFR expression in primary foci. Statistical analysis revealed that co-expression of p53 protein and EGFR was significantly correlated with LNM, tumor size and clinicopathologic stage, but no correlation was found between their co-expression and age or sex. Our findings suggest that overexpression of p53 protein or EGFR in PTC tends to be associated with a high frequency of LNM, increased tumor size and advanced clinicopathologic stage, and that co-expression of both p53 protein and EGFR may predispose to growth and progression of PTC. Our findings also suggest that p53 protein and EGFR expressions may be clinicopathologic and prognostic indicators of PTC.