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Results for “Pathologic response”

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PubMed1999

Overexpression of p53 protein associates decreased response to chemoradiotherapy in patients with esophageal carcinoma.

Induction chemoradiotherapy before esophagectomy for esophageal carcinoma seems to improve patient survival. Given the toxicity of this regimen, it would be useful to predict those patients likely to benefit. p53 is known to mediate apoptosis in response to DNA damage, but there are few data evaluating the relationship between p53 expression and chemoradiosensitivity in human tissues. We immunohistochemically evaluated p53 protein expression in 95 biopsy specimens from patients with esophageal carcinoma before chemoradiotherapy. p53 expression was correlated to the pathologic response identified in subsequent esophagectomy specimens. p53 immunoreactivity was recorded semiquantitatively using the following scale: neg, < 5%; 1+, 5-25%; 2+, 26-50%; 3+, 51-75%; 4+, > or = 76%. Pathologic response in esophagectomy specimens was categorized as overt residual tumor (ORT), minimal residual tumor, and no residual tumor. Of the 95 patients, 64 had adenocarcinoma, and 31 had squamous cell carcinoma. Of those with adenocarcinoma, 46 (72%) of 64 were positive for p53. Thirty-seven (80%) of 46 p53+ patients had ORT, compared with 4 (22%) of 18 p53- patients (P < .001). There was no correlation between the degree of p53 staining and pathologic response. Of those with squamous cell carcinoma, 13 (42%) of 18 were positive for p53. Three (23%) of 13 p53+ patients had ORT, compared with 4 (22%) of 18 p53- patients (P = .96). Our data indicate that overexpression of p53 protein is associated with decreased responsiveness to induction chemoradiotherapy in patients with esophageal adenocarcinoma but that no such association exists in patients with esophageal squamous cell carcinoma.

Adenocarcinoma↗

PubMed2001

Chemokine regulation of normal and pathologic immune responses.

Chemokines are small basic proteins that are the major mediators of all leukocyte migration. There are at least 46 distinct chemokines, and 19 chemokine receptors, making it easily the largest cytokine family. Chemokines can be both beneficial and harmful, by either stimulating an appropriate immune response to microbial invasion, or by mediating pathologic tissue destruction in many types of human disease. Chemokines have been implicated in the tissue destruction seen in autoimmune diseases, atherosclerosis, allograft rejection, and neoplasia. Chemokines also play essential roles in normal lymphocyte trafficking to primary and secondary lymphoid organs for antigen presentation and lymphocyte maturation. Chemokines also regulate hematopoietic stem and progenitor cell homing and proliferation. Therefore, it is likely that chemokines will become important targets for pharmacologic intervention in a wide variety of human diseases in the future.

Animals↗

PubMedDate not supplied

Epidoxorubicin and paclitaxel as primary chemotherapy for T > 3 cm and T4 breast cancer patients.

UNLABELLED: The Anthracyclines/Taxanes combination is often used in adjuvant and advanced breast cancer. PURPOSE: To evaluate the toxicity and pathological response of sequential epidoxorubicin/paclitaxel combination as primary chemotherapy for T > 3 cm and T4 breast cancer patients. PATIENTS AND METHODS: Forty-eight patients with T2 > 3 cm, T3 and T4 breast tumours were treated with Epidoxorubicin (90 mg/m2, i.v.) on day one and paclitaxel (200 mg/m2 over 3 hours) on day 2 every 21 days for four courses. After the fourth cycle the patients underwent modified radical mastectomy or quadrantectomy plus axillary lymph node dissection followed by six courses of intravenous CMF regimen (days 1 and 8, every 4 weeks). Radiotherapy was given to patients undergoing conservative surgery or with T4 cancers. Tamoxifen was administered in ER or PgR positive patients. RESULTS: Out of the 48 patients enrolled into this trial, 43 were evaluable for toxicity and pathological response. Primary chemotherapy with epidoxorubicin and paclitaxel was well tolerated: no heart toxicity was observed during primary chemotherapy and follow-up. Primary toxicity consisted of myalgia, grade 1 neuropathy and grade 3 alopecia. Disappearance of invasive tumours in the breast with node negative was observed in 11.6% of patients: pathological partial response was shown in 56% of patients. On the whole major pathological response was achieved in 67% of our series: in the remaining 33% we found a stable disease or a size reduction less than 50%. No progressive disease was observed. Conservative surgery was performed in 64.5% of T2 and T3 tumours. CONCLUSION: These preliminary data showed that the epidoxorubicin/paclitaxel combination was safe and effective as primary chemotherapy for patients with T > 3 cm and T4 breast cancer patients.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1996

Cellular immune response and pathology in schistosomiasis.

In the present review, some aspects of the cellular response following the murine Schistosoma mansoni infection are described. Due to the peculiar route used by the schistosome to infect its definitive host, the skin appears as a critical site in which the initial events of the host/parasite relationship occur and where the immune response is initiated. Moreover, the induction and the modulation of the granuloma formation, which represent the main aspect of the pathology of this parasitic disease, is under the control of several cellular populations n which CD4 and CD8 T cells play a key role. The cytokines produced in response to the parasite, such as IL7 in the skin and IFN gamma in the liver, seem to influence the further development of immunity against Schistosoma mansoni.

Animals↗

PubMed1999

Monitoring the response of patients with locally advanced breast carcinoma to neoadjuvant chemotherapy using [technetium 99m]-sestamibi scintimammography.

BACKGROUND: Mammographic and physical examination assessments of the response of locally advanced breast carcinoma (LABC) to neoadjuvant therapy have been shown to be inaccurate. The authors studied the feasibility and accuracy of [technetium 99m]-sestamibi (MIBI) for monitoring the response of patients with LABC to neoadjuvant chemotherapy. METHODS: Patients receiving neoadjuvant chemotherapy for LABC underwent prone lateral scintimammography before therapy, after 2 months of therapy, and close to the completion of chemotherapy (presurgery) if chemotherapy continued for >3 months. Images were analyzed both qualitatively and quantitatively using the lesion-to-normal breast MIBI uptake ratio (L:N). Imaging results were compared with the clinical response and the pathologic response as determined from the posttherapy surgical specimen. RESULTS: A total of 32 patients (29 who were assessable for primary tumor response and 28 who were assessable for lymph node response) were included in the study. The mean change in the primary tumor L:N MIBI uptake ratio after 2 months of chemotherapy was -35% for clinical responders and +17% for nonresponders (P<0.001). Patients achieving a pathologic primary tumor macroscopic complete response (CR) had a mean change in uptake on the presurgical scan of -58% versus -18% for patients with a partial response (P<0.005). A decrease of > or =40% in the MIBI uptake ratio identified CRs with 100% sensitivity and 89% specificity. Pretherapy imaging predicted axillary lymph node metastases in 85% of patients ultimately found to have > or =1 positive lymph nodes at surgery, but was less accurate in identifying residual lymph node disease after therapy (55% sensitivity and 75% specificity). CONCLUSIONS: MIBI imaging accurately assessed the response to neoadjuvant chemotherapy in patients with LABC. Further studies are needed to determine the role of MIBI in this group of patients.

Adult↗

PubMed1997

Experience with intraperitoneal cisplatin and etoposide and i.v. sodium thiosulphate protection in ovarian cancer patients with either pathologically complete response or minimal residual disease.

BACKGROUND: High-dose platinum-based regimens can produce responses in patients not responding to standard chemotherapy. As in many ovarian cancer patients the disease remains confined to the peritoneal cavity, intraperitoneal (i.p.) chemotherapy has been applied as an alternative approach to increase drug exposure. The delivery of cytotoxic agents to the peritoneal cavity can lead to high drug concentrations intraperitoneally with less systemic toxicity. This study aimed at evaluating the efficacy and toxicity of high-dose i.p. cisplatin plus etoposide and intravenous sodium thiosulphate protection in ovarian cancer. PATIENTS AND METHODS: Patients with either a pathologically complete response (pCR) after first-line treatment or with persistent disease after first-line platinum-based chemotherapy or abdominal recurrences were eligible. All intraabdominal lesions had to be < 2 cm at the start of i.p. treatment. The treatment consisted of etoposide 350 mg/m2 i.p. followed by cisplatin 200 mg/m2 i.p. with intravenous sodium thiosulphate (4 g/m2 bolus, followed by 12 g/m2 over six hours) protection. Four courses of i.p. treatment were administered in case of pCR and 6 courses otherwise, at four-weekly intervals. RESULTS: The study comprised 29 patients, six patients with pCR, 17 patients with persistent disease and six patients with abdominal recurrences. They received a total of 105 courses of treatment (65% of the scheduled number of courses). Twelve patients completed scheduled treatment, illustrating its feasibility. In 17 patients treatment had to be prematurely stopped because of inflow obstruction (seven patients), bowel perforation (two patients), renal toxicity (two patients), neurotoxicity (two patients), or malaise and vomiting (four patients). One patient with bowel perforation died of this complication. Severe nausea and vomiting occurred in 51% of cycles. Leukopenia and thrombopenia grade 3 and 4 occurred in 30% and 6% of cycles, respectively. Ototoxicity of cisplatin was measured by serial tone audiography in 23 patients: only eight patients (35%) showed significant audiographic changes, although none of them developed clinical hearing loss. Fifteen patients were evaluable for response: four pCR, five PR, two SD, four PD. The median duration of freedom from progression was 616 days and the median overall survival 1065 days from the start of treatment. CONCLUSIONS: High-dose i.p. treatment with cisplatin and etoposide can be associated with significant toxicities. Major clinical problems are nausea, vomiting, and the formation of intraabdominal adhesions. Intravenous sodium thiosulphate effectively reduces the systemic toxicity of high-dose cisplatin. The value of high-dose i.p. treatment is uncertain and its routine use cannot be recommended.

Adult↗

PubMed2000

Preoperative paclitaxel and radiotherapy for locally advanced breast cancer: surgical aspects.

INTRODUCTION: Approximately 15% of breast cancer patients present with large tumors that involve the skin, the chest wall, or the regional lymph nodes. Multimodality therapy is required, to provide the best chance for long-term survival. We have developed a regimen of paclitaxel, with concomitant radiation, as a primary therapy in patients with locally advanced breast cancer. METHODS: Eligible patients had locally advanced breast cancer (stage IIB or III). After obtaining informed consent, patients received paclitaxel (30 mg/m2 during 1 hour) twice per week for 8 weeks and radiotherapy to 45 Gy (25 fractions, at 180 cGy/fraction, to the breast and regional nodes). Patients then underwent modified radical mastectomy followed by postoperative polychemotherapy. RESULTS: Twenty-nine patients were enrolled. Of these, 28 were assessable for clinical response and toxicity, and 27 were assessable for pathological response. Objective clinical response was achieved in 89%. At the time of surgery, 33% had no or minimal microscopic residual disease. Chemoradiation-related acute toxicity was limited; however, surgical complications occurred in 41% of patients. CONCLUSIONS: Preoperative paclitaxel with radiotherapy is well tolerated and provides significant pathological response, in up to 33% of patients with locally advanced breast cancer, but with a significant postoperative morbidity rate.

Adult↗

PubMed1999

Preoperative chemoradiation with cisplatin and 5-fluorouracil for extraperitoneal T3 rectal cancer: acute toxicity, tumor response, sphincter preservation.

PURPOSE: To evaluate the impact of preoperative external radiation therapy intensified by systemic chemotherapy including bolus cisplatin (c-DDP) and 4-day infusional 5-fluorouracil (PLAFUR-4) on tumor response and sphincter preservation in patients with extraperitoneal T3 rectal cancer with acceptable toxicity, and to compare the results to our previous experience with bolus mitomycin c (MMC) and 4-day infusion 5-FU (FUMIR). METHODS AND MATERIALS: Between October 1995 and March 1998, 40 consecutive patients with resectable extraperitoneal adenocarcinoma of the rectum were treated with preoperative chemoradiation: slow infusion i.v. c-DDP, 60 mg/m2, day 1 and 29 plus 24-h continuous infusion i.v. 5-fluorouracil (5-FU) 1000 mg/m2, days 1-4 and 29-32, and concurrent external beam radiotherapy (45 Gy whole pelvis followed by 5.4 Gy boost). All but 3 patients had T3 disease. Surgery was performed 6-8 weeks after the end of chemoradiation. RESULTS: No patient had Grade 4 acute toxicity. Grade 3 hematological toxicity was observed only in 2 (5%) patients. No patient had major gastrointestinal, skin, or urological acute toxicity. All patients had radical surgery. There was no perioperative mortality; perioperative morbidity rate was 12%. Overall, 23% (9 of 40) of patients had a complete pathological response and 10% (4 of 40) of patients had rare isolated residual cancer cells (Tmic). Comparing the stage at the diagnostic workup with the pathological stage, tumor downstaging was observed in 27 (68%) patients; nodal status downstaging was detected in 24 (60%) patients. Thirty-four (85%) patients had a sphincter-saving surgical procedure. In 4 of 10 (40%) patients who were definitive candidates for an abdominoperineal resection (APR), the sphincter was preserved, as it was in 13 of 13 (100%) probable candidates. Lengthening of the distance between the anorectal ring and the lower pole of the tumor > or =20 mm was observed in 9 (23%) patients. None of the patients had soilage after the sphincter-saving procedure. In our previous experience with FUMIR the complete pathological response was 9%, the sphincter-saving surgical procedure was performed in 66% cases, and the Grade 3+ toxicity was observed in 13% of patients. CONCLUSIONS: The addition of c-DDP to 5-FU (PLAFUR-4) in a neoadjuvant radiochemotherapy schedule improved the pathological response rate in comparison with our previous experience. Toxicity was low indeed, thus we commenced another study adding one more day of 5-FU infusion (PLAFUR-5) to further improve our results.

Adult↗

PubMed2000

High dose radiation therapy and chemotherapy as induction treatment for stage III nonsmall cell lung carcinoma.

BACKGROUND: The current study was conducted to review the authors' experience in treating consecutive patients with American Joint Committee on Cancer (1997 revision) Stage III nonsmall cell lung carcinoma with aggressive preoperative chemoradiation followed by surgical resection. METHODS: The records of all patients who received preoperative chemoradiation were evaluated. Patients received 2 cycles of concurrent cisplatin and etoposide with 5940 centigrays of radiation therapy. They then were reevaluated to determine whether they were surgical candidates. If so, resection of the primary tumor with mediastinal lymph node dissection was performed 4-6 weeks after the completion of preoperative treatment. After adequate healing, an additional four cycles of cisplatin/etoposide or carboplatin/paclitaxel was given. RESULTS: Forty-two patients received preoperative chemoradiation, 33 of whom underwent surgical resection (79%), including 9 patients who underwent pneumonectomies. Complete pathologic responses were observed in 27% of these patients. Postoperative complications were noted in 21% of the patients and included persistent air leak, supraventricular arrhythmia, and empyema. There were no reported treatment-related deaths. The median follow-up was 26 months. The overall 5-year survival rate for all patients was 36.5% and was 45. 3% for patients who underwent resection. A trend toward increased 5-year survival was observed in patients who had a complete pathologic response (57.1%). Univariate analysis revealed the N stage classification to be significant for predicting a complete response. Patterns of failure revealed the brain to be the most common site of first recurrence (50%) and the only site of recurrence in 36% of patients. There was only one case of local failure. CONCLUSIONS: Preoperative chemoradiation using high radiation doses is feasible with acceptable toxicity. The results of the current study suggest an increased complete pathologic response rate and increased overall survival rate compared with reports in the published literature.

Adult↗

PubMed2001

Complete response to neoadjuvant chemoradiation for rectal cancer does not influence survival.

BACKGROUND: Up to 30% of patients with locally advanced rectal cancer have a complete clinical or pathologic response to neoadjuvant chemoradiation. This study analyzes complete clinical and pathologic responders among a large group of rectal cancer patients treated with neoadjuvant chemoradiation. METHODS: From 1987 to 2000, 141 consecutive patients with biopsy-proven, locally advanced rectal cancer were treated with preoperative 5-fluorouracil-based chemotherapy and radiation. Clinical restaging after treatment consisted of proctoscopic examination and often computed tomography scan. One hundred forty patients then underwent operative resection, with results tracked in a database. Standard statistical methods were used to examine the outcomes of those patients with complete clinical or pathologic responses. RESULTS: No demographic differences were detected between either clinical complete and clinical partial responders or pathologic complete and pathologic partial responders. The positive predictive value of clinical restaging was 60%, and accuracy was 82%. By use of the Kaplan-Meier life table analysis, clinical complete responders had no advantage in local recurrence, disease-free survival, or overall survival rates when compared with clinical partial responders. Pathologic complete responders also had no recurrence or survival advantage when compared with pathologic partial responders. Of the 34 pathologic T0 tumors, 4 (13%) had lymph node metastases. CONCLUSIONS: Clinical assessment of complete response to neoadjuvant chemoradiation is unreliable. Micrometastatic disease persists in a proportion of patients despite pathologic complete response. Observation or local excision for patients thought to be complete responders should be undertaken with caution.

Aged↗

PubMed1991

A preliminary report of combination chemotherapy with cisplatin and mitomycin-C followed by radical hysterectomy or radiation therapy in patients with locally advanced cervical cancer.

Neoadjuvant chemotherapy with cisplatin and mitomycin-C was used in the primary treatment of 17 patients with locally advanced cervical cancer (stages Ib-IIIb; tumor diameter greater than 5 cm) prior to definitive local treatment with radical hysterectomy or radiotherapy. Thirteen of the seventeen patients (76.5%) responded to initial chemotherapy, permitting a radical hysterectomy in ten patients. At histologic examination of the surgically resected primary tumor and lymph nodes, complete pathologic responses were found in 2 patients and partial pathologic responses in 8 patients. The median follow-up time is 14.5 months with a median survival for all patients of 52 weeks. All responders are alive. No therapy-related deaths, major complications, or delay in treatment occurred. Neoadjuvant chemotherapy with mitomycin-C and cisplatin is feasible and may be of benefit for patients with locally advanced cervical cancer.

Adult↗

PubMed2002

Primary chemotherapy with docetaxel for the management of breast cancer.

Several clinical trials have explored the efficacy of docetaxel (Taxotere) as primary chemotherapy for breast cancer. Docetaxel has been evaluated as single-agent therapy, sequentially as a single agent following anthracycline-containing regimens, and in combination with anthracyclines, cisplatin, and trastuzumab (Herceptin) in patients with high-risk early breast cancer. Two large, randomized phase III trials have demonstrated significant improvements in clinical and pathologic response rates with the sequential addition of docetaxel to an anthracycline-containing preoperative regimen. A trial conducted in the United Kingdom demonstrated that docetaxel sequential to CVAP (cyclophosphamide [Cytoxan, Neosar], vincristine, doxorubicin [Adriamycin], prednisolone) produced a higher overall clinical response rate (94% vs 66%, P = .001) and pathologic complete response rate (34% vs 18%) compared to additional cycles of CVAP as primary chemotherapy. This translated into a survival advantage for docetaxel-treated patients, whose 3-year disease-free and overall survival were significantly improved (97% vs 84%; 90% vs 77%, P = .03). The results of the National Surgical Adjuvant Breast and Bowel Project (NSABP) protocol B-27 demonstrated that primary doxorubicin/cyclophosphamide followed by docetaxel significantly increased the clinical complete response (65% vs 40%, P < .001) and pathologic complete response rates (25.6% vs 13.7%, P < .001) and decreased the rate of positive axillary nodes (40.5% vs 48.5%, P = .01). Final analysis of NSABP B-27 may also potentially demonstrate improved disease-free and overall survivals. Additional phase II and phase III randomized trials have compared docetaxel/anthracycline combinations with standard anthracycline-based regimens. Preliminary results have shown that incorporation of docetaxel can improve the rate of breast preservation surgery and the overall clinical and pathologic complete response rates.

Antineoplastic Agents, Phytogenic↗

PubMed1998

Pathologic amyloid beta-protein cell surface fibril assembly on cultured human cerebrovascular smooth muscle cells.

Cerebrovascular amyloid beta-protein (A beta) deposition is a key pathological feature of Alzheimer's disease and hereditary cerebral hemorrhage with amyloidosis-Dutch type (HCHWA-D). A beta(1-40) containing the E22Q HCHWA-D mutation, but not wild-type A beta(1-40), potently induces several pathologic responses in cultured human cerebrovascular smooth muscle cells, including cellular degeneration and a robust increase in the levels of cellular A beta precursor. In the present study, we show by several quantitative criteria, including thioflavin T fluorescence binding, circular dichroism spectroscopy, and transmission electron microscopic analysis, that at a concentration of 25 microM neither HCHWA-D A beta(1-40) nor wild-type A beta(1-40) appreciably assembles into beta-pleated sheet-containing fibrils in solution over a 6-day incubation period. In contrast, at the same concentrations, HCHWA-D A beta(1-40), but not wild-type A beta(1-40), selectively binds and assembles into abundant fibrils on the surfaces of cultured human cerebrovascular smooth muscle cells. The simultaneous addition of an equimolar concentration of the dye Congo red prevents the cell surface fibril assembly of HCHWA-D A beta(1-40). Moreover, Congo red effectively blocks the key pathologic responses induced by HCHWA-D A beta(1-40) in these cells. The present findings suggest that the surface of human cerebrovascular smooth muscle cells may selectively orchestrate the assembly of pathogenic A beta fibrils and that cell surface A beta fibril formation plays an important role in causing the pathologic responses in these cells.

Amyloid beta-Peptides↗

PubMed1999

[A study of clinical symptoms, muscle pathology, therapeutic response, and prognosis of myositis in patients with HTLV-1 associated myelopathy (HAM)].

Myositis is one of well-known complications of HTLV-1 associated myelopathy (HAM). On twelve HAM patients, 10 women and 2 men complicated with myositis, we examined their clinical symptoms, muscle pathology, and therapeutic response. Clinical examination revealed gait disturbance in 10, weakness of upper limbs in 6, muscle atrophy in 4, and myalgia in 3 patients. Blood test disclosed elevated serum CK level in 6 patients. Muscle biopsy showed marked inflammatory changes with many necrotic and degenerating fibers in 7 patients, and the rest showed only focal invasion of inflammatory cells. Eight patients received corticosteroid or immunosuppressant therapy. The neurological symptoms were improved in 5 of 8 patients 3 months after the treatment. And only one out of 5 patients whom we followed up 3 years after the treatment showed improvement.

Adult↗

PubMed1993

Growth hormone status in patients with maturation arrest of spermatogenesis.

The growth hormone levels of 11 azoospermic patients with histological evidence of maturation arrest of unknown aetiology were studied using the clonidine test. The results were compared with the results from clonidine tests on 10 healthy fertile men and on a group of patients with severe oligozoospermia of various aetiologies. The results demonstrated that 10 patients (91%) in the azoospermic group had non-reactive, pathological responses while none of the control group had a pathological response. Of the severe oligozoospermic group, 82% had normal reactive clonidine tests (P < 0.005). We suggest that growth hormone deficiency may be associated with maturation arrest, and the possibility of treatment with growth hormone should be considered.

Administration, Oral↗

PubMed1988

The prognostic and therapeutic value of second-look laparotomy in advanced ovarian cancer.

Of 267 patients with ovarian cancer FIGO stages III and IV, 157 underwent second-look laparotomy after combination chemotherapy consisting of cis-platinum and cyclophosphamide with and without doxorubicin. At second-look operation 45% had macroscopic tumour, 15% microscopic tumour, and 40% complete pathological response. Survival 3 years after second look was: complete pathological response 74%; microscopic disease 24%; visible tumour less than 1 cm 28%; visible tumour greater than 1 cm 17%; negative cytology 59%; and positive cytology 18%. Of the patients with macroscopic tumour, 29% had all visible tumour removed at second look. Three-year survival for these patients was about 45%.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2000

Autoantibody responses and pathology regulated by B7-1 and B7-2 costimulation in MRL/lpr lupus.

The activation of T lymphocytes requires both Ag-mediated signaling through the TCR as well as costimulatory signals transmitted through B7-1 and/or B7-2 with CD28. The interference of B7-mediated costimulatory signals has been proposed as one immunotherapeutic intervention for the prevention autoimmune disease. This study has examined autoantibody responses and autoimmune pathology in a murine model of human systemic lupus erythematosus (SLE), the MRL-lpr/lpr mouse, genetically deficient in B7-1 or B7-2, or in mice treated with B7-1/B7-2 blocking Abs. In contrast to other studies of murine models of SLE, MRL-lpr/lpr mice treated with B7 blocking Abs exhibit strong anti-small nuclear ribonucleoprotein (snRNP) and anti-DNA autoantibody responses with some changes in isotype switching as compared with untreated animals. All MRL-lpr/lpr mice deficient in B7-1 or B7-2 produce anti-snRNP and anti-DNA titers with isotypes virtually identical with wild-type animals. However, the absence of B7-2 costimulation did interfere with the spontaneous activation and the accumulation of memory CD4+ or CD8+ T lymphocytes characteristic of wild-type MRL-lpr/lpr mice. IgG and C3 complement deposition was less pronounced in the kidneys of B7-2 deficient MRL-lpr/lpr mice, reflecting their lessor degree of glomerulonephritis. By comparison, B7-1-deficient MRL-lpr/lpr mice had more severe IgG and C3 deposits in glomeruli.

Animals↗

PubMed1995

[Clinicopathological evaluation of etoposide or estramustine phosphate in castrated patients with advanced prostatic cancer].

BACKGROUND: We conducted a multicentric randomized trial to compare bilateral orchiectomy versus bilateral orchiectomy plus etoposide or estramustine phosphate as first-line therapy for advanced prostatic cancer (stage D2). METHODS: From January 1991 to December 1992 a total of 46 newly diagnosed cases (registered cases) of advanced (stage D2) prostatic cancer was randomized into 3 groups as follows; Group A: bilateral orchiectomy and 25 mg/day of etoposide every 2 weeks for 6 months. Group B: bilateral orchiectomy and 560 mg/day of estramustine phosphate for 6 months. Group C: bilateral orchiectomy alone. One of group A and one of group B were ineligible cases, so 44 were eligible. In the eligible cases, ages were ranged from 54 to 90 (mean of 71.2) years old. No significant difference of patients' characteristics was found among 3 groups and median follow-up period was 25 months. Response was evaluated based on the response criteria according to Japanese urological association. Specifically, a central pathologist who blinded to the treatment was employed for evaluating pathological response at six months. RESULTS: Of the 44 eligible patients, 33 and 25 were evaluated for clinically and pathological analyses, respectively. Clinical response rates were 80% (12/15) of group A, 100% (4/4) of group B and 78.6% (11/14) of group C. No significant difference in the clinical response and survival rate was shown among the three groups. Significantly higher frequencies of side effects were noted in the grop B compared to the other two groups (p < 0.05) and cardiovascular complications were the most frequent in group B. Favorable pathological response was obtained in all of group B, but not statistically significant compared with 7/21 (33.3%) of response rate in group A and C. The pathological response was significantly correlated with the clinical one in all patients (p < 0.01). While 8 of 11 patients (73%) with pathological response grade 1, 2 and 3 achieved clinical PR (partial response) or CR (complete response), only 5 of 14 (36%) with grade 0 received PR or CR. CONCLUSIONS: We conclude that low dose administration of etoposide or estramustine phosphate dose not improve clinical response and survival in a short term in castrated patients, but increases the adverse effects due to the drugs in these patients. In addition, the pathological evaluation at 6 months after treatment appears to reflect the clinical response at that time in newly diagnosed patients with advanced prostatic cancer.

Administration, Oral↗