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Biomedical subjects

J L Barrera

Publications and source records attributed to J L Barrera.

10 recordsLinked to original sources

A trial of IRX-2 in patients with squamous cell carcinomas of the head and neck.

A Phase II trial in 42 patients with squamous cell cancer of the head and neck (H and NSCC) was performed using a combination immunotherapy with 10-20 days of perilymphatic injections of a natural cytokine mixture (NCM: IRX-2; 200 units IL-2 equivalence) preceded by low dose cyclophosphamide (CY; 300 mg/m(2)) and followed by daily oral indomethacin (25 mg t.i.d.) and zinc (65 mg in a multivitamin preparation). Thirty-nine patients underwent subsequent surgical resection and 22 stage IV patients received additional radiotherapy. Forty-two percent were adjudged to have complete and partial clinical responses (>50% tumor reduction); an additional five patients had minor responses for a total of 58%. Comparison of post-treatment biopsies or surgical specimens showed 90% of patients had reduction in tumor area from 79% to 48% (over half of which was fragmented) and increased area of leukocyte infiltration from 9% to 32% (79% of which was lymphoid). The treatment with IRX-2 was not associated with significant side effects and 24 of patients showed improvement in eating, breathing or phonation or reduced pain and bleeding. Fifteen patients with lymphocytopenia (lymphocyte counts [LC] less than or equal to 1500 mm(3)) showed significant increases in LC, CD3+, CD4+ and CD8+ T lymphocytes of 401, 147, 95 and 100/mm(3), respectively. Analysis of outcome of 32 on protocol patients after 36 months versus 32 concurrent institutional H and NSCC controls showed delayed recurrences and significant increases in mean survival time (MST) and survival (p's<0.02). The data document immunotherapy induced regression of H and NSCC with delayed recurrence and improved mean survival time.

Adult↗

[Use of median fronto-naso-orbital flap to decrease the incidence of complications in patients undergoing craniofacial resection].

BACKGROUND: Resection of malignant neoplasms invading the anterior cranial base is performed with craniofacial resection (CFR) with acceptable results in complication rates and oncologic outcomes. However, still there are series with major morbidity in up to 40% of patients, and mortality of 5%. A retrospective study was performed to evaluate the results in terms of morbidity, mortality, function and aesthetics using a median fronto orbital flap (MFOF). METHODS: The MFOF was used in 28 consecutive patients who presented to the Head and Neck Service from 1992 to 1999, in the Instituto Nacional de Cancerología, Mexico City, and was combined with a superior rhinotomy for en bloc resection of the ethmoid complex in the last 12 cases. 89% of patients had malignant neoplasms. RESULTS: 1 death occurred in this series (3%) and the global morbidity was 35%. Aesthetics and function were good to excellent. Percentages of tumor-free survival for malignant lesions was 76% and 41% at 2 and 5 years follow up, respectively. CONCLUSION: CFR is a safe approach for treatment of neoplasms of the anterior skull base. MFOF mobilization decreases complication rates and gives superb exposure for en bloc resection of tumors invading the ethmoidomaxillary complex specially when combined with a superior rhinotomy. A positive impact on quality of life was obtained.

Adolescent↗

Involvement of chemokine receptors in breast cancer metastasis.

Breast cancer is characterized by a distinct metastatic pattern involving the regional lymph nodes, bone marrow, lung and liver. Tumour cell migration and metastasis share many similarities with leukocyte trafficking, which is critically regulated by chemokines and their receptors. Here we report that the chemokine receptors CXCR4 and CCR7 are highly expressed in human breast cancer cells, malignant breast tumours and metastases. Their respective ligands CXCL12/SDF-1alpha and CCL21/6Ckine exhibit peak levels of expression in organs representing the first destinations of breast cancer metastasis. In breast cancer cells, signalling through CXCR4 or CCR7 mediates actin polymerization and pseudopodia formation, and subsequently induces chemotactic and invasive responses. In vivo, neutralizing the interactions of CXCL12/CXCR4 significantly impairs metastasis of breast cancer cells to regional lymph nodes and lung. Malignant melanoma, which has a similar metastatic pattern as breast cancer but also a high incidence of skin metastases, shows high expression levels of CCR10 in addition to CXCR4 and CCR7. Our findings indicate that chemokines and their receptors have a critical role in determining the metastatic destination of tumour cells.

Actins↗

Combination immunotherapy of squamous cell carcinoma of the head and neck: a phase 2 trial.

OBJECTIVES: To test the efficacy of a natural cytokine mixture (IRX-2), cyclophosphamide, indomethacin, and zinc to induce immune regression of squamous cell carcinoma (SCC) of the head and neck (H&N) prior to conventional therapy and to characterize the responses. PATIENTS AND DESIGN: A phase 2 trial was performed in 15 adults with recently diagnosed, biopsy-confirmed H&N SCC (3 with stage II disease, 6 with stage III disease, and 6 with stage IV disease). The patients were treated with 20 days of perilymphatic injections of IRX-2 (administered subcutaneously at the base of the skull) in combination with contrasuppression consisting of a low-dose infusion of cyclophosphamide (300 mg/m2), and daily oral indomethacin and zinc (StressTabs) in a 21-day cycle before surgery and/or radiotherapy. Tumor dimensions, toxic effects, and disease-free survival were monitored. The tumor sections were histologically examined after surgery, and tumor reduction, fragmentation, and lymphoid infiltration were assessed. RESULTS: All 15 patients responded clinically to the 21-day IRX-2 protocol: 1 with a complete response, 7 with a partial response, and 7 with a minor response. All 15 patients responded pathologically with tumor reduction (mean, 42%) and fragmentation (mean, 50%) in the histological section and increased lymphoid infiltration. The adverse effects of the IRX-2 protocol were negligible except for an allergic skin rash (n = 1) and parotiditis (n = 1). Indomethacin caused gastritis in 1 patient. Reduction of pain and ulceration and bleeding were observed in 8 and 4 patients, respectively. Four of 5 patients with lymphopenia showed increased CD3, CD4, and CD8 cell counts. After surgery (n = 13) and/or radiotherapy (n = 10) and with a mean follow-up of 17 months, 3 patients have had recurrences, 1 patient has died of disease, 1 patient has been re-treated with immunotherapy and has no evidence of disease, and 1 patient is alive with disease. Two patients died of other causes with no evidence of disease. CONCLUSIONS: The IRX-2 immunotherapy induced lymphocyte mobilization and infiltration in H&N SCC associated with clinical and histological tumor responses indicative of immune regression in all 15 patients. Minimal toxic effects were observed, and overall survival may have been improved. A phase 3 trial seems warranted.

Adult↗

Lingual ulceration.

Explore the source record for details and available documents.

Carcinoma, Squamous Cell↗

Histologic findings in patients with head and neck squamous cell carcinoma receiving perilymphatic natural cytokine mixture (IRX-2) prior to surgery.

OBJECTIVE: To induce tumor regression with immunotherapy and to characterize the histology. SETTING: National Institute of Cancerology, Mexico City, Mexico. PATIENTS: Thirteen patients with advanced squamous cell carcinoma of the head and neck region. INTERVENTION: A 21-day cycle of preoperative immunotherapy, including a single intravenous infusion of low-dose cyclophosphamide (300 mg/M2), 10 daily perilymphatic injections of a natural cytokine mixture (approximately 150 units interleukin-2 equivalence by enzyme-linked immunosorbent assay), daily oral indomethacin, and daily oral zinc with multivitamins. OUTCOME MEASURES: Pretreatment biopsies were performed to confirm the diagnosis and to characterize the lesion by standard pathologic criteria, including the degree of tumor-associated lymphocytes. Clinical responses were assessed at surgery, and the specimen was analyzed with respect to changes in tumor morphology and lymphoid and inflammatory infiltration (T and B lymphocytes, plasma cells, macrophages, granulocytes, and giant cells). The presurgical and postsurgical characteristics were ascribed percentages based on a representative section. RESULTS: Prior to treatment, on average the biopsies demonstrated 77% solid tumor with 14% stroma and 9% sparse infiltration of lymphocytes. After treatment, one patient had a complete clinical response and showed only residual inflammatory cells and fibrosis. One patient had no clinical or histologic response. Of the remaining 11 patients, 4 had partial, 6 had minor, and 1 had no response. Tumors were reduced an average of 41% (16% solid and 25% fragmented) and lymphoid infiltration increased to 45% without change in residual stroma. CONCLUSIONS: The pathologic changes viewed in the context of the clinical findings indicate that this immunotherapy protocol induces immune regression of the tumor, mediated predominantly by T and B lymphocytes, and thus elicits a tumor-specific immune reaction.

Aged↗

Stenosis of the colon.

Seven cases of colonic stenosis due to an infectious, parasitic or ischemic origin are reported. Particular emphasis is laid on the need for an early differential diagnosis from Hirschsprung's disease.

Chloramphenicol↗

Osteosarcoma of the jaw.

BACKGROUND: Osteogenic sarcoma of the jaw has clinical and prognostic differences from that of long bones. METHODS: We reviewed 23 confirmed cases of osteosarcoma of the jaw seen at the Instituto Nacional de Cancerologia of Mexico between 1972 and 1990. RESULTS: Fifty-seven percent of the patients were women. Median age for all patients was 28 years. In 52% of cases, the neoplasm involved the maxilla. Tumor size ranged from 5 to 24 cm (median 10 x 7 cm) and 87% of the neoplasms were grade III or IV (Broder's). Twenty one (91%) patients were treated with surgery (s); radiotherapy (Rt) was administered to 14 (61%) and chemotherapy (Ct) to 11 (48%) patients. Clear (negative) surgical margins were obtained in 43% of surgically treated patients. Median follow-up for 20 patients eligible for evaluation was 16.5 months. Survival at 5 years was 10%. CONCLUSIONS: We found that tumor size and surgical margins were significant prognostic factors. Early diagnosis of these tumors is mandatory to improve survival; the role of Ct and Rt is still unknown.

Adolescent↗

A natural cytokine mixture (IRX-2) and interference with immune suppression induce immune mobilization and regression of head and neck cancer.

Prior studies indicate that combination immunotherapy of squamous cell cancer (SCC) of head and neck (H&N) with cytokines is feasible (Hadden et al., 1994). To induce immune regression of H&N SCC 20 stage II-IV patients received 3 weeks prior to surgery low dose cyclophosphamide (300 mg/M2), then 10 daily perilymphatic injections of a natural cytokine mixture (IRX-2)(150 units of IL-2 equivalence) and daily oral indomethacin and zinc. Tumor responses, T-lymphocyte and subset counts, and toxicity were monitored. Six patients had major clinical responses (both complete [CR] and partial [PR]) without major toxicity. Five of 20 patients were lymphocytopenic (1242 +/- 88 mm3) prior to treatment and the immunotherapy induced marked significant increases in total lymphocyte counts, CD3+ T-cells, and both CD4+ and CD8+ T-cells as well as a population of CD3+, CD4-, and CD8- lymphocytes. The post treatment specimen of 18/20 patients showed histologically tumor fragmentation, overall reduction and diffuse infiltration with lymphocytes and plasma cells. Histologic tumor reductions in these patients averaged 44% and the lymphoid infiltration increased 4.7 fold from 9-42%. The immune infiltration of the tumor reflects varying degrees of both T- and B-cells and indicates immunization to the tumor. The immunization achieved may improve clinical control of H&N SCC by improving the possibility that surgical resection of advanced loco-regional disease will leave no viable tumor.

Antineoplastic Combined Chemotherapy Protocols↗