Jaime Garza - Academia.edu (original) (raw)
Papers by Jaime Garza
Journal of Oral and Maxillofacial Surgery, 1999
Journal of Ethnopharmacology, 2002
A crude ethanolic extract of Cupressus lusitanica Mill. leaves demonstrate cytotoxicity in a pane... more A crude ethanolic extract of Cupressus lusitanica Mill. leaves demonstrate cytotoxicity in a panel of cancer cell lines. Cell death was due to apoptosis, as assessed by morphologic features (chromatin condensation and apoptotic bodies formation) and specific DNA fragmentation detected by in situ end-labeling of DNA breaks (TUNEL). The apoptotic cell death was induced timely in a dose-dependent manner. Despite the absence of changes in the expression levels of antiapoptotic protein Bcl-2, proapoptotic Bax protein variants v and d were increased. These results warrant further research of possible antitumor compounds in this plant.
Journal of Clinical Oncology, 2010
Mexico (CONACyT-Mé xico 44395 and 71276). Roche Laboratories (Mexico City) provided all-trans ret... more Mexico (CONACyT-Mé xico 44395 and 71276). Roche Laboratories (Mexico City) provided all-trans retinoic acid as a donation, with no interference in the trial design and results analysis.
International Journal of Surgical Pathology, 1999
... DOI: 10.1177/106689699900700405 1999 7: 227 INT J SURG PATHOL Abelardo Meneses, Alejandro Moh... more ... DOI: 10.1177/106689699900700405 1999 7: 227 INT J SURG PATHOL Abelardo Meneses, Alejandro Mohar, Jaime de la Garza, Jae Y. Ro and Alberto G. Ayala Well-Differentiated Intramedullary Osteosarcoma : A Report of Five Cases Published by: ...
International Journal of Radiation Oncology*Biology*Physics, 2003
Chemoradiation based on cisplatin, most commonly weekly, is the standard treatment of locally adv... more Chemoradiation based on cisplatin, most commonly weekly, is the standard treatment of locally advanced cervical cancer; however, the nephrotoxic potential and the requirement for hydration of cisplatin somewhat restrains its use. The objective of this study was to determine the recommended dose of carboplatin when administered weekly during pelvic radiation (RT). Twenty-four histologically proven, International Federation of Gynecology and Obstetrics Stage IIIB patients were treated with standard pelvic RT concurrently with six weekly applications of carboplatin at the following dose levels: 100 mg/m(2), 116 mg/m(2), 133 mg/m(2), and 150 mg/m(2). Six patients per level were treated. Acute toxicity was assessed according to the Radiation Therapy Oncology Group Acute Radiation Morbidity Scoring Criteria. The recommended dose was defined as the one that was one level below the level at which dose-limiting toxicity was present in more than one-third of patients. Between September 2001 and July 2002, 24 patients were accrued. All but two completed external beam radiotherapy and intracavitary treatment. The treatment was well tolerated. The median number of weekly applications of carboplatin was six, and the mean dose to points A and B was 85.6 Gy (range 75.2-91.6) and 62.9 Gy (range 58.2-74.6), respectively. RT was delivered within 41.7 days (range 33-70). Dose-limiting toxicity (leukopenia and/or neutropenia) was present in 50% of patients treated at the higher dose level (150 mg/m(2)). At the recommended dose of 133 mg/m(2), 33% of patients presented with Grade 3 leukopenia. At treatment completion, 75% of patients had a complete clinical response. Carboplatin at 133 mg/m(2), weekly for 6 weeks, is a well tolerated and effective radiosensitizer in cervical cancer patients.
International Journal of Radiation Oncology*Biology*Physics, 2005
To compare gemcitabine and cisplatin (GC) with cisplatin (C) concurrent with radiotherapy in Inte... more To compare gemcitabine and cisplatin (GC) with cisplatin (C) concurrent with radiotherapy in International Federation of Gynecology and Obstetrics Stage IB2, IIA, and IIB cervical carcinoma in a preoperative setting. The main endpoints were the pathologic response rate and toxicity. A total of 83 patients were randomized to either C or GC. Treatment consisted of six doses of cisplatin at 40 mg/m(2) every week for Arm 1 (C) and six doses of gemcitabine at 125 mg/m(2) plus cisplatin at 40 mg/m(2) every week for or Arm 2 (GC) Both regimens were administered concurrent with 50 Gy of external beam radiotherapy in 2-Gy fractions for 5 weeks. After chemoradiotherapy, patients underwent radical hysterectomy. All 83 patients were studied for toxicity and 80 for response. The complete pathologic response rate in the C arm and GC arm was 55% (95% confidence interval, 35.5-73%) and 77.5% (95% confidence interval, 57-90%; p = 0.0201). Among those with a partial response, 7 patients each had high and intermediate-high risk factors for recurrence in their surgical specimens in the C arm vs. 2 and 3 patients, respectively, with these characteristics in the CG arm. The number of weekly doses and the dose intensity of GC were lower than for C. The time to complete external beam radiotherapy also favored the C arm. The CG combination produced greater GI and hematologic toxicity. The radiosensitizing combination of GC achieved a greater pathologic response rate than C in the treatment of cervical cancer.
International Journal of Radiation Oncology*Biology*Physics, 2011
Background: Brain metastases occur in 30-50% of Non-small cell lung cancer (NSCLC) patients and c... more Background: Brain metastases occur in 30-50% of Non-small cell lung cancer (NSCLC) patients and confer a worse prognosis and quality of life. These patients are usually treated with Whole-brain radiotherapy (WBRT) followed by systemic therapy. Few studies have evaluated the role of chemoradiotherapy to the primary tumor after WBRT as definitive treatment in the management of these patients. Methods: We reviewed the outcome of 30 patients with primary NSCLC and brain metastasis at diagnosis without evidence of other metastatic sites. Patients were treated with WBRT and after induction chemotherapy with paclitaxel and cisplatin for two cycles. In the absence of progression, concurrent chemoradiotherapy for the primary tumor with weekly paclitaxel and carboplatin was indicated, with a total effective dose of 60 Gy. If disease progression was ruled out, four chemotherapy cycles followed. Results: Median Progression-free survival (PFS) and Overall survival (OS) were 8.43 ± 1.5 and 31.8 ± 15.8 months, respectively. PFS was 39.5% at 1 year and 24.7% at 2 years. The 1-and 2-year OS rates were 71.1 and 60.2%, respectively. Three-year OS was significantly superior for patients with N0-N1 stage disease vs. N2-N3 (60 vs. 24%, respectively; Response rate [RR], 0.03; p= 0.038).
International Journal of Gynecological Cancer, 2001
Neoadjuvant chemotherapy followed by surgery is a promising approach in locally advanced cervical... more Neoadjuvant chemotherapy followed by surgery is a promising approach in locally advanced cervical carcinoma. The aim of this study was to evaluate the feasibility, technical aspects, and clinical results of surgery after induction chemotherapy in this patient population. Forty-one untreated cervical carcinoma patients staged as IB2 to IIIB received three 21-day courses of cisplatin 100mg/m2 on day 1 and gemcitabine 1000 mg/m2 on days 1 and 8 followed by surgery or concomitant chemoradiation. The response to chemotherapy, operability, surgical/pathological findings, disease-free period, and survival of the surgically treated patients were evaluated. All 41 patients were evaluated for toxicity and 40 were evaluated for response. The overall objective response rate was 95% (95% confidence interval 88%-100%), and was complete in three patients (7.5%) and partial in 35 (87.5%). Granulocytopenia grades 3/4 occurred in 13.8% and 3.4% of the courses, respectively, whereas nonhematological toxicity was mild. Twenty-three patients underwent type III radical hysterectomy. Mean duration of surgery was 3.8 h (range 2:30-5:20), median estimated blood loss was 670 ml and median hospital stay was 5.2 days. Intraoperative complications occurred in one case (venous injury). In all but one case the resection margins were negative. Four patients (17%) had positive nodes (one node each); six (26%) had complete pathologic response, three (13%) had microscopic; and 14 (60%) macroscopic residual disease. At 24 months of maximum follow-up (median 20), the disease-free and overall survival rates were 59% and 91%, respectively. Induction chemotherapy with cisplatin/gemcitabine produced a high response rate and did not increase the difficulty of surgery. Operating time, blood loss, intraoperative complications, and hospital stay were all within the range observed for type III hysterectomy in early stage patients. We therefore conclude that type III radical hysterectomy is feasible in locally advanced cervical cancer patients who respond to chemotherapy.
International Immunopharmacology, 2002
Clinical and experimental data demonstrate that local cytokines are able to induce tumor regressi... more Clinical and experimental data demonstrate that local cytokines are able to induce tumor regression and in some cases antitumor systemic immune response. IRX-2 is a cell-free mixture of cytokines obtained from unrelated donor lymphocytes with demonstrated ability to induce immune mediated regression of squamous cell carcinomas of head and neck. The objective of this study was to evaluate the antitumor activity and toxicity of IRX-2 in untreated early stage cervical cancer patients. Ten consecutive patients clinically staged IB1, IB2 and IIA were treated with a neoadjuvant immunotherapy regimen that consisted in a single IV dose of cyclophosphamide at 300 mg/m2 on day 1, oral indomethacin or ibuprofen and zinc sulfate were administered from days I to 21 and 10 regional perilymphatic injections of IRX-2 on days 3 to 14. All patients were scheduled for radical hysterectomy on day 21. The clinical and pathological responses, toxicity and survival were evaluated. Clinical response was seen in 50% of patients (three partial responses, two minor responses). Seven patients underwent surgery and pathological tumor reduction associated with tumor fragmentation was found in five cases. Histological studies demonstrated a rather heterogeneous cell type infiltrating pattern in the tumor which included lymphocytes, plasma cells, neutrophils, macrophages and eosinophils. Immunohistochemical analysis of the surgical specimens demonstrated an increase of tumor infiltrating CD8+ cells. The treatment was well tolerated except for mild pain and minor bleeding during injections and gastric intolerance to indomethacin. At 31 months of maximum follow-up (median 29), eight patients are disease-free. Our results suggest that the immunotherapy approach used induces tumor responses in cervical cancer patients. Further studies are needed to confirm these results as well as to elucidate the mechanisms underlying these effects.
International Immunopharmacology, 2003
A Phase II trial in 42 patients with squamous cell cancer of the head and neck (H and NSCC) was p... more 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.
International Immunopharmacology, 2003
To determine if lymph nodes (LN) of patients receiving IRX-2 immunotherapy reflect changes in his... more To determine if lymph nodes (LN) of patients receiving IRX-2 immunotherapy reflect changes in histology. National Cancer Institute, Mexico City, Mexico. Thirty patients with advanced squamous cell carcinoma of the head and neck (H and N SCC) and 10 non-cancer controls. A 21-day cycle of preoperative immunotherapy, including a single intravenous infusion of low-dose cyclophosphamide (300 mg/M(2)), 10 or 20 daily perilymphatic injections of a natural cytokine mixture (IRX-2) (approximately 200 U interleukin-2 equivalence by enzyme-linked immunosorbent assay), daily oral indomethacin, and daily oral zinc with multivitamins, followed by surgery (20 patients); surgery only (10 patients); LN biopsy controls (10). Pretreatment biopsies were performed to confirm the diagnosis. Clinical responses were assessed at surgery, and the specimen and a sample of lymph node were analyzed with respect to changes in morphology and lymphoid and inflammatory infiltration (T and B lymphocytes, plasma cells, macrophages, granulocytes, and giant cells). The postsurgical characteristics were ascribed percentages based on a representative section and compared. All 20 H and N SCC patients treated with IRX-2 showed the changes of immune regression of their tumors, previously characterized [Arch. Pathol. Lab. Med. 122 (1998) 447]. The 10 H and N SCC controls showed no such changes. Lymph node histology of the 10 H and N SCC controls showed, compared to non-cancer controls, reduced size, decreased T cell area and density and increased sinus histiocytosis. The lymph nodes of IRX-2-treated H and N SCC patients showed increased size (over both control groups), increased T cell area and density and decreased follicles and sinus histiocytosis. The T cell and/or B cell areas of LN of IRX-2-treated patients showed a high correlation with T and/or B cell infiltration into these tumors (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001). The lymph nodes of patients with H and N SCC are distinguished by T cell depletion and sinus histiocytosis (SH). Immunotherapy reverses these changes and induces nodal expansion and lymphoid infiltration into the tumor that correlates with LN changes. The correlation of nodal expansion with tumor lymphoid infiltration and regression implies an effective immunization to host tumor antigens occurring at the level of the regional lymph node. The reversal of sinus histiocytosis, by IRX-2 treatment, in association with nodal expansion suggests that tumor antigen processing via dendritic cells is defective in cancer-bearing patients and that it is corrected by the treatment.
Experimental Cell Research, 1998
The nuclear matrix is the nonchromatin protein structural component of the nucleus that governs n... more The nuclear matrix is the nonchromatin protein structural component of the nucleus that governs nuclear shape and also exerts regulatory control over higher order gene organization. Recent studies have documented the presence of tumor-associated nuclear matrix proteins in several human cancers. We used high-resolution two-dimensional gel electrophoresis to compare nuclear matrix protein patterns in cervical carcinomas with those from normal cervical tissue. Tumors obtained from 20 patients undergoing hysterectomy for clinically localized cervical cancer were compared with normal cervical tissue. We have identified five polypeptides (CvC-1: M r ؍ 69,408 Da, pI ؍ 5.78; CvC-2: M r ؍ 53,752 Da, pI ؍ 5.54; CvC-3: M r ؍ 47,887 Da, pI ؍ 5.60; CvC-4: M r ؍ 46,006 Da, pI ؍ 5.07; and CvC-5: M r ؍ 44,864 Da, pI ؍ 6.61) in the nuclear matrix from cervical carcinomas that were present in 20 of 20 cervical tumors but 0 of 10 normal tissues. These data extend similar findings of cancer-associated nuclear matrix proteins in other human cancers and suggest that nuclear matrix proteins may represent a new class of cancer markers that could aid the diagnosis or management of some types of cancer.
Clinical and Translational Oncology, 2008
Male pseudohermaphroditism and androgen insensitivity syndrome cases have an increased risk of de... more Male pseudohermaphroditism and androgen insensitivity syndrome cases have an increased risk of developing testicular cancer due to many factors such as mutations, hormonal disturbances involving gonadotropins and cryptorchidism. We describe the clinical features, diagnosis and treatment of two cases with partial androgen insensitivity syndrome and testicular cancer development, which were handled at the National Cancer Institute of Mexico.
Cancer Treatment Reviews, 2003
Radiation was until recently the key and only modality for the routine treatment of locally advan... more Radiation was until recently the key and only modality for the routine treatment of locally advanced cervical carcinoma. However after years of studying multi-modality treatments as an alternative to radiation alone in randomized phase III trials, the standard treatment has changed to chemo-radiation based on cisplatin. Three recent meta-analyses have confirmed that cisplatin-based chemo-radiation adds an absolute 12% benefit in five-year survival over radiation therapy alone. Neoadjuvant chemotherapy followed by radiation has not been of proven benefit, but when neoadjuvant chemotherapy is followed by surgery, an absolute increase of 15% in five-year survival over radiation alone is seen. This benefit in survival is comparable to that obtained with the current chemo-radiation schedules based on cisplatin. Despite these encouraging results there remains room for improvement as the five-year survival of patients treated with chemo-radiation ranges from nearly 80% in bulky IB tumours to only 25% in stage IVA disease. Other therapeutic approaches need to be fully evaluated including the use of chemo-radiation after neoadjuvant chemotherapy; the use of new drug combinations and the multi-modality combination of neoadjuvant chemotherapy followed by radical surgery plus adjuvant chemo-radiation. Likewise, the addition of radiosensitizers to cisplatin, preoperative chemo-radiation and/or adjuvant chemotherapy may eventually improve the currents results of cisplatin-based chemo-radiation. Nevertheless, it is hard to foresee a dramatic increase in cure rate, even with the most optimal combination of cytotoxic drugs, surgery and radiation, and thus the testing of molecular targeted therapies against cervical cancer is a logical step to follow.
Cancer Treatment Reviews, 2008
Renal cell carcinoma represents nearly 3% of all cancers, predominantly affecting individuals P50... more Renal cell carcinoma represents nearly 3% of all cancers, predominantly affecting individuals P50 years of age, and until recently, few treatments options were available for metastatic disease. The 5-year median survival for these patients with metastatic renal cell carcinoma has been estimated at <10%. This review explores the data of the most relevant trials focusing on new approaches with novel agents, including sunitinib, sorafenib, bevacizumab, temsirolimus, as well as their combinations with traditional agents. We describe mechanisms of action, activity, and toxicity profile of those agents, as well as administration schedules that have been studied in clinical trials.
Cancer Chemotherapy and Pharmacology, 2005
Oxaliplatin (cis-[(1R,2R)-1,2-cyclohexanediamine-N,N&amp;amp;amp;amp;amp;amp;amp;amp;amp;... more Oxaliplatin (cis-[(1R,2R)-1,2-cyclohexanediamine-N,N&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;] [oxalato(2-)-O,O&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;] platinum; Eloxatin) is a third-generation platinum compound with a 1,2-diaminocyclohexane (DACH) carrier ligand, which has a wide spectrum of anticancer activity in vitro systems and has displayed preclinical and clinical activity in a wide variety of tumors. To investigate its in vitro activity against head and neck cancer, we exposed two head and neck cancer cell lines to the compound, created a variant resistant to cisplatin to study cross-resistance to the compound and analyzed the potential radiosensitizing effect of the drug. We report here that oxaliplatin was cytotoxic at similar doses to cisplatin in these cells. There was no cross-resistance to cisplatin, as demonstrated by different IC50 values in these cell lines and the sensitivity to oxaliplatin of the cisplatin-resistant cell line. There was an effective radiosensitizer effect of the compound in either cell line. Additional in vitro and in vivo experimentation is warranted in order to support the use of oxaliplatin as a radiosensitizer in head and neck cancer patients.
Cancer, 2008
The incidence of breast cancer in Latin American countries is lower than that in more developed c... more The incidence of breast cancer in Latin American countries is lower than that in more developed countries, whereas the mortality rate is higher. These differences probably are related to differences in screening strategies and access to treatment. Population-based data are needed to make informed decisions. A 65-question telephone survey that included 100 breast cancer experts from 12 Latin American countries was conducted in 2006 as an exploratory analysis of the current state of breast cancer treatment in these regions at both at the country level and at the center level. Greater than 90% of countries had no national law or guideline for mammography screening. The access rate to mammography was 66.3% at the country level and 47% at the center level. Variation in care based on level (country vs center) was indicated for the timing of treatment after diagnosis, timing from initial diagnosis to treatment, and the time from surgery to initial chemotherapy. However, the more sophisticated diagnostic testing for hormone receptors and biomarkers were available at most centers (>80%), and, overall, nearly 80% of patients started treatment within 3 months of diagnosis. Variation in care between breast cancer care at the center level versus the country level indicated a need for national cancer care programs. Alternative data collection strategies for understanding the state of breast cancer control programs in developing countries can help identify areas of improvement. Cancer 2008;113(8 suppl):2359-65.
BMC Cancer, 2009
Background: Central nervous system is a common site of metastasis in NSCLC and confers worse prog... more Background: Central nervous system is a common site of metastasis in NSCLC and confers worse prognosis and quality of life. The aim of this prospective study was to evaluate the prognostic significance of clinical-pathological factors (CPF), serum CEA levels, and EGFR and HER2 tissueexpression in brain metastasis (BM) and overall survival (OS) in patients with advanced NSCLC.
Archives of Medical Research, 2008
Background. We undertook this study to determine the diagnostic accuracy of 18 FDG after three cy... more Background. We undertook this study to determine the diagnostic accuracy of 18 FDG after three cycles and at the end of chemotherapy in non-Hodgkin's lymphoma (NHL) or Hodgkin's lymphoma (HL). We also evaluated the role of 67 Ga, bone marrow aspiration (BMA), and computed tomography (CT) in monitoring lymphoma treatment. Methods. 18 FDG, 67 Ga, BMA, and CT were performed before chemotherapy on 40 untreated patients. 18 FDG and CT data were also obtained in 28/40 patients after 3 cycles of chemotherapy and at the end of chemotherapy. Patients had a median follow-up of 18 months, 21 had NHL, 7 had HL. Age range was from 15 to 74 years. Histopathology considered the standard reference at the initial stage. Follow-up was a comparative study of all exam results. Results. Initial staging for PET and CT was as follows: sensitivity (Se) was 100%, specificity (Sp) 100%, positive predictive value (PPV) 100%, negative predictive value (NPV) 0%, and accuracy (Ac) 100%. 67 Ga was Se, 64%; Sp, 0%, PPV, 100 %; and Ac, 64%. After the third cycle of chemotherapy and at the end of chemotherapy, Se, Sp, PPV, NPV, and Ac were always higher with PET than with CT. Eighteen patients had complete response, and seven had partial or no response. Conclusions. 18 FDG had greater prognostic values than CT after the third and last cycle of chemotherapy. PET after three cycles of chemotherapy is predictive of 18-month outcome in patients with intermediate and aggressive NHL and HL and may help in the identification of patients who would benefit from more intensive treatment or from a change in chemotherapy. Ó
Journal of Oral and Maxillofacial Surgery, 1999
Journal of Ethnopharmacology, 2002
A crude ethanolic extract of Cupressus lusitanica Mill. leaves demonstrate cytotoxicity in a pane... more A crude ethanolic extract of Cupressus lusitanica Mill. leaves demonstrate cytotoxicity in a panel of cancer cell lines. Cell death was due to apoptosis, as assessed by morphologic features (chromatin condensation and apoptotic bodies formation) and specific DNA fragmentation detected by in situ end-labeling of DNA breaks (TUNEL). The apoptotic cell death was induced timely in a dose-dependent manner. Despite the absence of changes in the expression levels of antiapoptotic protein Bcl-2, proapoptotic Bax protein variants v and d were increased. These results warrant further research of possible antitumor compounds in this plant.
Journal of Clinical Oncology, 2010
Mexico (CONACyT-Mé xico 44395 and 71276). Roche Laboratories (Mexico City) provided all-trans ret... more Mexico (CONACyT-Mé xico 44395 and 71276). Roche Laboratories (Mexico City) provided all-trans retinoic acid as a donation, with no interference in the trial design and results analysis.
International Journal of Surgical Pathology, 1999
... DOI: 10.1177/106689699900700405 1999 7: 227 INT J SURG PATHOL Abelardo Meneses, Alejandro Moh... more ... DOI: 10.1177/106689699900700405 1999 7: 227 INT J SURG PATHOL Abelardo Meneses, Alejandro Mohar, Jaime de la Garza, Jae Y. Ro and Alberto G. Ayala Well-Differentiated Intramedullary Osteosarcoma : A Report of Five Cases Published by: ...
International Journal of Radiation Oncology*Biology*Physics, 2003
Chemoradiation based on cisplatin, most commonly weekly, is the standard treatment of locally adv... more Chemoradiation based on cisplatin, most commonly weekly, is the standard treatment of locally advanced cervical cancer; however, the nephrotoxic potential and the requirement for hydration of cisplatin somewhat restrains its use. The objective of this study was to determine the recommended dose of carboplatin when administered weekly during pelvic radiation (RT). Twenty-four histologically proven, International Federation of Gynecology and Obstetrics Stage IIIB patients were treated with standard pelvic RT concurrently with six weekly applications of carboplatin at the following dose levels: 100 mg/m(2), 116 mg/m(2), 133 mg/m(2), and 150 mg/m(2). Six patients per level were treated. Acute toxicity was assessed according to the Radiation Therapy Oncology Group Acute Radiation Morbidity Scoring Criteria. The recommended dose was defined as the one that was one level below the level at which dose-limiting toxicity was present in more than one-third of patients. Between September 2001 and July 2002, 24 patients were accrued. All but two completed external beam radiotherapy and intracavitary treatment. The treatment was well tolerated. The median number of weekly applications of carboplatin was six, and the mean dose to points A and B was 85.6 Gy (range 75.2-91.6) and 62.9 Gy (range 58.2-74.6), respectively. RT was delivered within 41.7 days (range 33-70). Dose-limiting toxicity (leukopenia and/or neutropenia) was present in 50% of patients treated at the higher dose level (150 mg/m(2)). At the recommended dose of 133 mg/m(2), 33% of patients presented with Grade 3 leukopenia. At treatment completion, 75% of patients had a complete clinical response. Carboplatin at 133 mg/m(2), weekly for 6 weeks, is a well tolerated and effective radiosensitizer in cervical cancer patients.
International Journal of Radiation Oncology*Biology*Physics, 2005
To compare gemcitabine and cisplatin (GC) with cisplatin (C) concurrent with radiotherapy in Inte... more To compare gemcitabine and cisplatin (GC) with cisplatin (C) concurrent with radiotherapy in International Federation of Gynecology and Obstetrics Stage IB2, IIA, and IIB cervical carcinoma in a preoperative setting. The main endpoints were the pathologic response rate and toxicity. A total of 83 patients were randomized to either C or GC. Treatment consisted of six doses of cisplatin at 40 mg/m(2) every week for Arm 1 (C) and six doses of gemcitabine at 125 mg/m(2) plus cisplatin at 40 mg/m(2) every week for or Arm 2 (GC) Both regimens were administered concurrent with 50 Gy of external beam radiotherapy in 2-Gy fractions for 5 weeks. After chemoradiotherapy, patients underwent radical hysterectomy. All 83 patients were studied for toxicity and 80 for response. The complete pathologic response rate in the C arm and GC arm was 55% (95% confidence interval, 35.5-73%) and 77.5% (95% confidence interval, 57-90%; p = 0.0201). Among those with a partial response, 7 patients each had high and intermediate-high risk factors for recurrence in their surgical specimens in the C arm vs. 2 and 3 patients, respectively, with these characteristics in the CG arm. The number of weekly doses and the dose intensity of GC were lower than for C. The time to complete external beam radiotherapy also favored the C arm. The CG combination produced greater GI and hematologic toxicity. The radiosensitizing combination of GC achieved a greater pathologic response rate than C in the treatment of cervical cancer.
International Journal of Radiation Oncology*Biology*Physics, 2011
Background: Brain metastases occur in 30-50% of Non-small cell lung cancer (NSCLC) patients and c... more Background: Brain metastases occur in 30-50% of Non-small cell lung cancer (NSCLC) patients and confer a worse prognosis and quality of life. These patients are usually treated with Whole-brain radiotherapy (WBRT) followed by systemic therapy. Few studies have evaluated the role of chemoradiotherapy to the primary tumor after WBRT as definitive treatment in the management of these patients. Methods: We reviewed the outcome of 30 patients with primary NSCLC and brain metastasis at diagnosis without evidence of other metastatic sites. Patients were treated with WBRT and after induction chemotherapy with paclitaxel and cisplatin for two cycles. In the absence of progression, concurrent chemoradiotherapy for the primary tumor with weekly paclitaxel and carboplatin was indicated, with a total effective dose of 60 Gy. If disease progression was ruled out, four chemotherapy cycles followed. Results: Median Progression-free survival (PFS) and Overall survival (OS) were 8.43 ± 1.5 and 31.8 ± 15.8 months, respectively. PFS was 39.5% at 1 year and 24.7% at 2 years. The 1-and 2-year OS rates were 71.1 and 60.2%, respectively. Three-year OS was significantly superior for patients with N0-N1 stage disease vs. N2-N3 (60 vs. 24%, respectively; Response rate [RR], 0.03; p= 0.038).
International Journal of Gynecological Cancer, 2001
Neoadjuvant chemotherapy followed by surgery is a promising approach in locally advanced cervical... more Neoadjuvant chemotherapy followed by surgery is a promising approach in locally advanced cervical carcinoma. The aim of this study was to evaluate the feasibility, technical aspects, and clinical results of surgery after induction chemotherapy in this patient population. Forty-one untreated cervical carcinoma patients staged as IB2 to IIIB received three 21-day courses of cisplatin 100mg/m2 on day 1 and gemcitabine 1000 mg/m2 on days 1 and 8 followed by surgery or concomitant chemoradiation. The response to chemotherapy, operability, surgical/pathological findings, disease-free period, and survival of the surgically treated patients were evaluated. All 41 patients were evaluated for toxicity and 40 were evaluated for response. The overall objective response rate was 95% (95% confidence interval 88%-100%), and was complete in three patients (7.5%) and partial in 35 (87.5%). Granulocytopenia grades 3/4 occurred in 13.8% and 3.4% of the courses, respectively, whereas nonhematological toxicity was mild. Twenty-three patients underwent type III radical hysterectomy. Mean duration of surgery was 3.8 h (range 2:30-5:20), median estimated blood loss was 670 ml and median hospital stay was 5.2 days. Intraoperative complications occurred in one case (venous injury). In all but one case the resection margins were negative. Four patients (17%) had positive nodes (one node each); six (26%) had complete pathologic response, three (13%) had microscopic; and 14 (60%) macroscopic residual disease. At 24 months of maximum follow-up (median 20), the disease-free and overall survival rates were 59% and 91%, respectively. Induction chemotherapy with cisplatin/gemcitabine produced a high response rate and did not increase the difficulty of surgery. Operating time, blood loss, intraoperative complications, and hospital stay were all within the range observed for type III hysterectomy in early stage patients. We therefore conclude that type III radical hysterectomy is feasible in locally advanced cervical cancer patients who respond to chemotherapy.
International Immunopharmacology, 2002
Clinical and experimental data demonstrate that local cytokines are able to induce tumor regressi... more Clinical and experimental data demonstrate that local cytokines are able to induce tumor regression and in some cases antitumor systemic immune response. IRX-2 is a cell-free mixture of cytokines obtained from unrelated donor lymphocytes with demonstrated ability to induce immune mediated regression of squamous cell carcinomas of head and neck. The objective of this study was to evaluate the antitumor activity and toxicity of IRX-2 in untreated early stage cervical cancer patients. Ten consecutive patients clinically staged IB1, IB2 and IIA were treated with a neoadjuvant immunotherapy regimen that consisted in a single IV dose of cyclophosphamide at 300 mg/m2 on day 1, oral indomethacin or ibuprofen and zinc sulfate were administered from days I to 21 and 10 regional perilymphatic injections of IRX-2 on days 3 to 14. All patients were scheduled for radical hysterectomy on day 21. The clinical and pathological responses, toxicity and survival were evaluated. Clinical response was seen in 50% of patients (three partial responses, two minor responses). Seven patients underwent surgery and pathological tumor reduction associated with tumor fragmentation was found in five cases. Histological studies demonstrated a rather heterogeneous cell type infiltrating pattern in the tumor which included lymphocytes, plasma cells, neutrophils, macrophages and eosinophils. Immunohistochemical analysis of the surgical specimens demonstrated an increase of tumor infiltrating CD8+ cells. The treatment was well tolerated except for mild pain and minor bleeding during injections and gastric intolerance to indomethacin. At 31 months of maximum follow-up (median 29), eight patients are disease-free. Our results suggest that the immunotherapy approach used induces tumor responses in cervical cancer patients. Further studies are needed to confirm these results as well as to elucidate the mechanisms underlying these effects.
International Immunopharmacology, 2003
A Phase II trial in 42 patients with squamous cell cancer of the head and neck (H and NSCC) was p... more 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.
International Immunopharmacology, 2003
To determine if lymph nodes (LN) of patients receiving IRX-2 immunotherapy reflect changes in his... more To determine if lymph nodes (LN) of patients receiving IRX-2 immunotherapy reflect changes in histology. National Cancer Institute, Mexico City, Mexico. Thirty patients with advanced squamous cell carcinoma of the head and neck (H and N SCC) and 10 non-cancer controls. A 21-day cycle of preoperative immunotherapy, including a single intravenous infusion of low-dose cyclophosphamide (300 mg/M(2)), 10 or 20 daily perilymphatic injections of a natural cytokine mixture (IRX-2) (approximately 200 U interleukin-2 equivalence by enzyme-linked immunosorbent assay), daily oral indomethacin, and daily oral zinc with multivitamins, followed by surgery (20 patients); surgery only (10 patients); LN biopsy controls (10). Pretreatment biopsies were performed to confirm the diagnosis. Clinical responses were assessed at surgery, and the specimen and a sample of lymph node were analyzed with respect to changes in morphology and lymphoid and inflammatory infiltration (T and B lymphocytes, plasma cells, macrophages, granulocytes, and giant cells). The postsurgical characteristics were ascribed percentages based on a representative section and compared. All 20 H and N SCC patients treated with IRX-2 showed the changes of immune regression of their tumors, previously characterized [Arch. Pathol. Lab. Med. 122 (1998) 447]. The 10 H and N SCC controls showed no such changes. Lymph node histology of the 10 H and N SCC controls showed, compared to non-cancer controls, reduced size, decreased T cell area and density and increased sinus histiocytosis. The lymph nodes of IRX-2-treated H and N SCC patients showed increased size (over both control groups), increased T cell area and density and decreased follicles and sinus histiocytosis. The T cell and/or B cell areas of LN of IRX-2-treated patients showed a high correlation with T and/or B cell infiltration into these tumors (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001). The lymph nodes of patients with H and N SCC are distinguished by T cell depletion and sinus histiocytosis (SH). Immunotherapy reverses these changes and induces nodal expansion and lymphoid infiltration into the tumor that correlates with LN changes. The correlation of nodal expansion with tumor lymphoid infiltration and regression implies an effective immunization to host tumor antigens occurring at the level of the regional lymph node. The reversal of sinus histiocytosis, by IRX-2 treatment, in association with nodal expansion suggests that tumor antigen processing via dendritic cells is defective in cancer-bearing patients and that it is corrected by the treatment.
Experimental Cell Research, 1998
The nuclear matrix is the nonchromatin protein structural component of the nucleus that governs n... more The nuclear matrix is the nonchromatin protein structural component of the nucleus that governs nuclear shape and also exerts regulatory control over higher order gene organization. Recent studies have documented the presence of tumor-associated nuclear matrix proteins in several human cancers. We used high-resolution two-dimensional gel electrophoresis to compare nuclear matrix protein patterns in cervical carcinomas with those from normal cervical tissue. Tumors obtained from 20 patients undergoing hysterectomy for clinically localized cervical cancer were compared with normal cervical tissue. We have identified five polypeptides (CvC-1: M r ؍ 69,408 Da, pI ؍ 5.78; CvC-2: M r ؍ 53,752 Da, pI ؍ 5.54; CvC-3: M r ؍ 47,887 Da, pI ؍ 5.60; CvC-4: M r ؍ 46,006 Da, pI ؍ 5.07; and CvC-5: M r ؍ 44,864 Da, pI ؍ 6.61) in the nuclear matrix from cervical carcinomas that were present in 20 of 20 cervical tumors but 0 of 10 normal tissues. These data extend similar findings of cancer-associated nuclear matrix proteins in other human cancers and suggest that nuclear matrix proteins may represent a new class of cancer markers that could aid the diagnosis or management of some types of cancer.
Clinical and Translational Oncology, 2008
Male pseudohermaphroditism and androgen insensitivity syndrome cases have an increased risk of de... more Male pseudohermaphroditism and androgen insensitivity syndrome cases have an increased risk of developing testicular cancer due to many factors such as mutations, hormonal disturbances involving gonadotropins and cryptorchidism. We describe the clinical features, diagnosis and treatment of two cases with partial androgen insensitivity syndrome and testicular cancer development, which were handled at the National Cancer Institute of Mexico.
Cancer Treatment Reviews, 2003
Radiation was until recently the key and only modality for the routine treatment of locally advan... more Radiation was until recently the key and only modality for the routine treatment of locally advanced cervical carcinoma. However after years of studying multi-modality treatments as an alternative to radiation alone in randomized phase III trials, the standard treatment has changed to chemo-radiation based on cisplatin. Three recent meta-analyses have confirmed that cisplatin-based chemo-radiation adds an absolute 12% benefit in five-year survival over radiation therapy alone. Neoadjuvant chemotherapy followed by radiation has not been of proven benefit, but when neoadjuvant chemotherapy is followed by surgery, an absolute increase of 15% in five-year survival over radiation alone is seen. This benefit in survival is comparable to that obtained with the current chemo-radiation schedules based on cisplatin. Despite these encouraging results there remains room for improvement as the five-year survival of patients treated with chemo-radiation ranges from nearly 80% in bulky IB tumours to only 25% in stage IVA disease. Other therapeutic approaches need to be fully evaluated including the use of chemo-radiation after neoadjuvant chemotherapy; the use of new drug combinations and the multi-modality combination of neoadjuvant chemotherapy followed by radical surgery plus adjuvant chemo-radiation. Likewise, the addition of radiosensitizers to cisplatin, preoperative chemo-radiation and/or adjuvant chemotherapy may eventually improve the currents results of cisplatin-based chemo-radiation. Nevertheless, it is hard to foresee a dramatic increase in cure rate, even with the most optimal combination of cytotoxic drugs, surgery and radiation, and thus the testing of molecular targeted therapies against cervical cancer is a logical step to follow.
Cancer Treatment Reviews, 2008
Renal cell carcinoma represents nearly 3% of all cancers, predominantly affecting individuals P50... more Renal cell carcinoma represents nearly 3% of all cancers, predominantly affecting individuals P50 years of age, and until recently, few treatments options were available for metastatic disease. The 5-year median survival for these patients with metastatic renal cell carcinoma has been estimated at <10%. This review explores the data of the most relevant trials focusing on new approaches with novel agents, including sunitinib, sorafenib, bevacizumab, temsirolimus, as well as their combinations with traditional agents. We describe mechanisms of action, activity, and toxicity profile of those agents, as well as administration schedules that have been studied in clinical trials.
Cancer Chemotherapy and Pharmacology, 2005
Oxaliplatin (cis-[(1R,2R)-1,2-cyclohexanediamine-N,N&amp;amp;amp;amp;amp;amp;amp;amp;amp;... more Oxaliplatin (cis-[(1R,2R)-1,2-cyclohexanediamine-N,N&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;] [oxalato(2-)-O,O&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;] platinum; Eloxatin) is a third-generation platinum compound with a 1,2-diaminocyclohexane (DACH) carrier ligand, which has a wide spectrum of anticancer activity in vitro systems and has displayed preclinical and clinical activity in a wide variety of tumors. To investigate its in vitro activity against head and neck cancer, we exposed two head and neck cancer cell lines to the compound, created a variant resistant to cisplatin to study cross-resistance to the compound and analyzed the potential radiosensitizing effect of the drug. We report here that oxaliplatin was cytotoxic at similar doses to cisplatin in these cells. There was no cross-resistance to cisplatin, as demonstrated by different IC50 values in these cell lines and the sensitivity to oxaliplatin of the cisplatin-resistant cell line. There was an effective radiosensitizer effect of the compound in either cell line. Additional in vitro and in vivo experimentation is warranted in order to support the use of oxaliplatin as a radiosensitizer in head and neck cancer patients.
Cancer, 2008
The incidence of breast cancer in Latin American countries is lower than that in more developed c... more The incidence of breast cancer in Latin American countries is lower than that in more developed countries, whereas the mortality rate is higher. These differences probably are related to differences in screening strategies and access to treatment. Population-based data are needed to make informed decisions. A 65-question telephone survey that included 100 breast cancer experts from 12 Latin American countries was conducted in 2006 as an exploratory analysis of the current state of breast cancer treatment in these regions at both at the country level and at the center level. Greater than 90% of countries had no national law or guideline for mammography screening. The access rate to mammography was 66.3% at the country level and 47% at the center level. Variation in care based on level (country vs center) was indicated for the timing of treatment after diagnosis, timing from initial diagnosis to treatment, and the time from surgery to initial chemotherapy. However, the more sophisticated diagnostic testing for hormone receptors and biomarkers were available at most centers (>80%), and, overall, nearly 80% of patients started treatment within 3 months of diagnosis. Variation in care between breast cancer care at the center level versus the country level indicated a need for national cancer care programs. Alternative data collection strategies for understanding the state of breast cancer control programs in developing countries can help identify areas of improvement. Cancer 2008;113(8 suppl):2359-65.
BMC Cancer, 2009
Background: Central nervous system is a common site of metastasis in NSCLC and confers worse prog... more Background: Central nervous system is a common site of metastasis in NSCLC and confers worse prognosis and quality of life. The aim of this prospective study was to evaluate the prognostic significance of clinical-pathological factors (CPF), serum CEA levels, and EGFR and HER2 tissueexpression in brain metastasis (BM) and overall survival (OS) in patients with advanced NSCLC.
Archives of Medical Research, 2008
Background. We undertook this study to determine the diagnostic accuracy of 18 FDG after three cy... more Background. We undertook this study to determine the diagnostic accuracy of 18 FDG after three cycles and at the end of chemotherapy in non-Hodgkin's lymphoma (NHL) or Hodgkin's lymphoma (HL). We also evaluated the role of 67 Ga, bone marrow aspiration (BMA), and computed tomography (CT) in monitoring lymphoma treatment. Methods. 18 FDG, 67 Ga, BMA, and CT were performed before chemotherapy on 40 untreated patients. 18 FDG and CT data were also obtained in 28/40 patients after 3 cycles of chemotherapy and at the end of chemotherapy. Patients had a median follow-up of 18 months, 21 had NHL, 7 had HL. Age range was from 15 to 74 years. Histopathology considered the standard reference at the initial stage. Follow-up was a comparative study of all exam results. Results. Initial staging for PET and CT was as follows: sensitivity (Se) was 100%, specificity (Sp) 100%, positive predictive value (PPV) 100%, negative predictive value (NPV) 0%, and accuracy (Ac) 100%. 67 Ga was Se, 64%; Sp, 0%, PPV, 100 %; and Ac, 64%. After the third cycle of chemotherapy and at the end of chemotherapy, Se, Sp, PPV, NPV, and Ac were always higher with PET than with CT. Eighteen patients had complete response, and seven had partial or no response. Conclusions. 18 FDG had greater prognostic values than CT after the third and last cycle of chemotherapy. PET after three cycles of chemotherapy is predictive of 18-month outcome in patients with intermediate and aggressive NHL and HL and may help in the identification of patients who would benefit from more intensive treatment or from a change in chemotherapy. Ó