Tumor Response to Neoadjuvant Chemotherapy Correlates with the Expression of P-Glycoprotein and PCNA but Not GST-π in the Tumor Cells of Cervical Carcinoma

Objective.To identify the clinicopathological and chemoresistant factors predicting the response to neoadjuvant chemotherapy and the patient prognosis in high-risk cervical carcinomas.Methods.We retrospectively reviewed 47 patients with locally advanced or bulky cervical carcinoma treated with two courses of intraarterial infusion of cisplatin, doxorubicin, mitomycin C, and 5-fluorouracil (5-FU), followed by radical hysterectomy at our hospital between 1988 and 1995. Expressions of the chemoresistance-related proteins, such as P-glycoprotein, glutathioneS-transferase π (GST-π), and proliferating cell nuclear antigen (PCNA) in the tumor cells, were examined by immunohistochemistry using pretreatment biopsy specimens. These results were compared with the chemotherapeutic response, which was evaluated by magnetic resonance imaging (MRI) and histopathology. Outcome of the patients was also studied.Results.Chemotherapeutic effect of either complete (CR) or partial (PR) response on MRI was obtained in 36 of the 47 (86%) patients. Poor response to chemotherapy was significantly correlated with P-glycoprotein expression (P< 0.005) and low PCNA labeling (P< 0.05), but not GST-π expression in the tumor cells. Independent prognostic factors for patient survival were parametrial involvement and lymph node metastasis. Neither the expression of GST-π nor PCNA was correlated with the patient survival.Conclusion.Assessment of the expression of P-glycoprotein and PCNA is potentially useful for the prediction of tumor response to neoadjuvant chemotherapy for cervical carcinomas.     

DSM-III-R personality disorders in outpatients with non-bipolar depression: The frequency in a sample of Japanese and the relationship to the 4-month outcome under adequate antidepressant therapy

Summary We investigated the frequency of personality disorders (PDs) and the relationship between the pressence of PD and the 4-month outcome of depression under adequate antidepressant therapy in a Japanese sample of 96 outpatients with non-bipolar major depression. The diagnosis of PD was made using a structured interiew method (the Structured Clinical Interview for DSM-III-R Personality Disorders) and after severe depressive symptoms were reduced. Any one kind of PD was found in 54.2% of the saple. The most frequent was avidant (34–4%), obsessived-compulsive (22.9%), narcisstic (18.8%), and dependent (16.7%) PDs. The frequencies of these PDs in our study except narcisstic PD, were about the same as those reported in previous studies with a matched setting for the PD diagnosis. Compared with patients without PD, a worse outcome was found in patients with PD, especially patients with multiple PDs from multiple PD clussters. There was no evidence that a specific PD or PD cluster especially worsens the outcome of depression.     

Role of β2 integrins in glomerular leucocytes in Henoch-Schoenlein purpura nephritis: an age-matched comparative study with immunoglobulin A nephropathy

SUMMARY: A comparative immunohistological study was performed for the glomerular deposition of complements (C1q and C3c), fibrin/fibrinogen‐related antigen (FRA), the expression of intercellular adhesion molecule‐1 (ICAM‐1), and the infiltration of leucocytes bearing β₂ integrins (leucocyte function associated antigen‐1 (LFA‐1), complement receptor 3 (CR3) and complement receptor 4 (CR4)) on renal biopsy specimens from 49 cases with Henoch‐Schoenlein purpura nephritis (HSPN), and 49 age‐matched cases with immunoglobulin A nephropathy (IgAN). the glomerular expression of ICAM‐1 was signifcantly correlated with the glomerular infiltration of leucocyte function associated antigen (LFA)‐1⁺ leucocytes in both diseases, and with that of CR3⁺ leucocytes in HSPN. the expression of ICAM‐1 was closely localized with the infiltration of LFA‐1⁺ leucocytes in the study with double immunostaining. the incidence and intensity of glomerular deposition of FRA were significantly higher in HSPN than in IgAN (P< 0.001), and those of C3c were significantly lower in HSPN than in IgAN (P< 0.001). the glomerular deposition of FRA was significantly correlated with the glomerular infiltration of CR4⁺ leucocytes in HSPN (P<0.05) but not in IgAN. In contrast, the glomerular deposition of C3c was significantly correlated with the glomerular infiltration of CR4⁺ leucocytes in IgAN (P<0.05), but not in HSPN. Studies with double immunostaining revealed a close association of CR4⁺ leucocytes with FRA deposition in HSPN and with C3c deposition in IgAN, respectively. the number of glomerular leucocytes bearing β₂ integrins was significantly correlated with urinary protein at the time of renal biopsy in both diseases. These results suggested the differential roles of β₂ integrins in the induction of glomerular injury in HSPN and IgAN. the ICAM‐1/LFA‐1 interaction may commonly be involved in the glomerular infiltration of leucocytes in both diseases. the ICAM‐1/CR3 interaction may be involved only in HSPN. Complement receptor 4 may function as a fibrin/fibrinogen receptor in HSPN, while CR4 may function as a complement receptor in IgAN.     

Frequent loss of heterozygosity for loci on chromosome 8p in hepatocellular carcinoma, colorectal cancer, and lung cancer.

Frequent loss of heterozygosity at chromosomal loci in a specific tumor type may indicate the presence of a tumor suppressor gene. We have examined loss of heterozygosity on chromosome 8p in paired tumor and constitutional DNA from 346 patients representing seven different types of human cancer. Frequent allelic losses were observed in hepatocellular carcinoma (22 of 46 cases, 47.8%), in colorectal cancer (12 of 26, 46.2%), and in non-small cell lung cancer (14 of 35, 40.0%), in contrast to low frequencies detected in breast cancer (5 of 56, 8.9%) and renal cell carcinoma (2 of 27, 7.4%). Ovarian cancer and gastric cancer showed intermediate frequencies of 33.3% and 22.2%. Subsequent analysis of 120 hepatocellular carcinomas and 94 colorectal cancers with five polymorphic markers along the short arm of chromosome 8 defined commonly deleted regions within the same chromosomal interval, 8p23. 1-8p21.3, suggesting that one or more tumor suppressor genes for both cancers may be present in that region.     

Clinical studies on the transabdominal resection of esophagocardial cancer and cervical anastomosis using bypass methods. Analysis of data on 76 patients

Transabdominal resection for esophagocardial cancer and reestablishment of alimentary continuity using bypass methods were performed in 76 patients. Thirteen underwent a bypass with a gastric tube and in 30, a colonic segment was prepared. In the remaining 33, a jejunal segment was used as a bypass organ, with considerable success. The 5 year survival rates were 68.8 per cent in those with stages (I+II), 16.5 per cent in those with stage III, 12.6 per cent in those with stage IV and 22.5 per cent in all cases, indicating similar results compared to those with cancer located in the upper third of the stomach with the limited proximal extension within the esophagocardial junction and operated on during the same period.     

Combination adoptive immunotherapy with chemoradiotherapy in oral carcinomas

Background The antitumor effects of adoptive immunotherapy in combination with chemoradiotherapy were investigated in patients with oral squamous cell carcinoma. Methods Inductive chemoradiotherapy with peplomycin, 5-fluorouracil and⁶⁰Co was given to 56 patients [CRI(−)group]. A local injection of adoptive lymphokine-activated killer (LAK) cells (≈2×10⁸ cells) and small doses of interleukin-2(≈3×10⁵ U) and interferon-gamma (≈2×10⁵U) was given to 40 other patients in combination with the chemoradiotherapy [CRI(+) group]. Results Clinically, CR, PR, and LR were observed in 15 (37.5%), 24 (60.0%), and 1 (2.5%) of the patients in the CRI (+) group, respectively; and in 14 (25.0%), 38 (67.9%), and 4 of the patients (7.1%) in the CRI (−) group. The histopathological effects were correlated with the tumor remission rate, with lethal degeneration (grades III and IV), and prominent degeneration (grade IIB) in the tumor cells noted in 20 (50.0%) and 16 (40.0%) of the CRI(+) patients, respectively; and in 21 (37.5%) and 29 (51.8%) of the CRI (−) patients. Immunohistochemically, a prominent decrease of proliferating cell nuclear antigenpositive cells with a reciprocal increase of Le^Y-positve cells was induced by the chemoradioimmunotherapy. DNA fragmentation was observed in the mutant type p53-negative tumors in the CRI(+) group. Conclusion Adoptive immunotherapy with LAK cells and cytokines in combination with chemoradiotherapy induces advantageous anticancer effects resulting from necrosis and apoptosis.     

Metastatic Behavior and Tumorigenicity of a Human Melanoma Cell Line (MM-RU) after Injection into Nude Mice

The ability of the human amelanotic melanoma cell line MM-RU to produce experimental metastases and to grow tumors at subcutaneous inoculation sites in 4-week-old nude mice was examined. After i.v. inoculation of 10⁶ cells, all injected mice (n=21) developed consistent numbers of metastatic pulmonary colonies within 32 days. The coefficients of variation for the number of colonies were between 17%–23% in three independent experiments. Survival time after i.v. inoculation was 63 ± 7 days (mean ± SD) (n=20). Within 20 days, subcutaneous inoculation of 5 × 10⁶ cells resulted in tumor growths of 13 ± 3 mm (mean ± SD) at the inoculation sites in all nude mice (n=12). The MM-RU cell line seems to be a simple, fast vehicle for testing the effect of melanoma growth modulators on experimental pulmonary metastases as well as on subcutaneously growing melanoma.     

The effect of hyperoxia on the lungs of rats deficient in essential fatty acids

Morphological alterations in the lungs of rats deficient in either or both of vitamin E and essential fatty acids were investigated after exposure to hyperoxia for 48h. In rats deficient in both vitamin E and essential fatty acids, there was damage to type-2 alveolar cells observed as swollen mitochondria and bleb formation in the cytoplasm. None of these changes was found in rats deficient in only one of these substances. Hyperoxia in rats deficient in both substance also caused destruction of the capillary endothelial cells and edema in the interstitium. The lungs of rats deficient in only one of the substances showed some edema in the capillary endothelial cells, but not destruction, and less interstitial edema. These findings suggest that simultaneous deficiency in vitamin E and essential fatty acids facilitates lung damage in rats exposed to hyperoxia.(Murakami R, Obara H, Momota T et al.: The effect of hyperoxia on the lungs of rats deficient in essential fatty acids. J Anesth 3: 149–154, 1989)     

A cysteine-activated protease isolated from Todarodes pacificus squid degrades collagen below its denaturation temperature

Collagen purified from the mantle muscle of the Japanese common squid, Todarodes pacificus, showed autodegradation during incubation under acidic conditions at 25 degrees C, without the addition of exogenous enzymes. This suggests that the collagenolytic proteases bind to collagen tightly through the steps of collagen preparation. Collagenolytic activity also was detected in a crude extract of mantle muscle, and leupeptin and E-64 were observed to inhibit collagenolytic activity within the collagen fraction and muscle extract. We purified these collagenolytic cysteine proteases by leupeptin column chromatography and cellulose acetate membrane electrophoresis. Optimal enzymatic activity was observed at pH 3.5, and collagenolytic activity was completely suppressed at neutral or alkaline pH. The purified enzymes were 28 kDa and 25 kDa in size, and both had gelatinolytic activity, as detected by gelatin zymography, and cut the specific site of denatured collagen alpha chain. The purified enzymes degraded squid collagen at 25 degrees C, which is 2.5 degrees lower than the temperature at which squid collagen normally denatures; however, the proteases were ineffective at 20 degrees C. Interestingly, the isolated proteases were capable of digesting both squid and bovine gelatin. In this article, we describe collagenolytic cysteine proteases that bind to the collagen of Todarodes pacificus, thereby digesting it by attacking microunfolding regions generated by incubation 2-3 degrees C below the denaturation temperature.