Immunomodulatory effects of low dose chemotherapy and perspectives of its combination with immunotherapy

Given that cancer is one of the main causes of death worldwide, many efforts have been directed toward discovering new treatments and approaches to cure or control this group of diseases. Chemotherapy is the main treatment for cancer; however, a conventional schedule based on maximum tolerated dose (MTD) shows several side effects and frequently allows the development of drug resistance. On the other side, low dose chemotherapy involves antiangiogenic and immunomodulatory processes that help host to fight against tumor cells, with lower grade of side effects. In this review, we present evidence that metronomic chemotherapy, based on the frequent administration of low or intermediate doses of chemotherapeutics, can be better than or as efficient as MTD. Finally, we present some data indicating that noncytotoxic concentrations of antineoplastic agents are able to both up-regulate the immune system and increase the susceptibility of tumor cells to cytotoxic T lymphocytes. Taken together, data from the literature provides us with sufficient evidence that low concentrations of selected chemotherapeutic agents, rather than conventional high doses, should be evaluated in combination with immunotherapy. Copyright © 2012 UICC.

Terapia ocupacional modulando a dor em pacientes oncológicos sob cuidados paliativos

Pós-graduação em Pesquisa e Desenvolvimento (Biotecnologia Médica) - FMB

Avaliação do tempo para acesso ao tratamento do câncer de mama no Distrito Federal

Pós-graduação em Ginecologia, Obstetrícia e Mastologia - FMB

Vivências de pacientes com câncer em cuidados paliativos e o significado da espiritualidade

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Tc-99m-sestamibi scintigraphy used to evaluate tumor response to neoadjuvant chemotherapy in locally advanced breast cancer: A quantitative analysis

To evaluate the tumor response to neoadjuvant chemotherapy, Tc-99m-sestamibi breast scintigraphy was proposed as a quantitative method Fifty-five patients with ductal carcinoma were studied They underwent breast scintigraphy before and after neoadjuvant chemotherapy, along with clinical assessment and surgical specimen analysis The regions of interest on the lesion and contralateral breast were identified, and the pixel counts were used to evaluate lesion uptake in relation to background radiation The ratio of these counts before to after neoadjuvant chemotherapy was assessed The decrease in uptake rate due to chemotherapy characterized the scintigraphy tumor response The Kruskal-Wallis test was used to compare the mean scintigraphic tumor response and histological type Dunn's multiple comparison test was used to detect differences between histological types The Mann-Whitney test was used to compare means between quantitative and qualitative variables scintigraphic tumor response vs clinical response and uptake before chemotherapy vs scintigraphic tumor response The Spearman's test was used to correlate the quantitative variables of clinical reduction in tumor size and scintigraphic tumor response All of the variables compared presented significant differences The change in Tc-99m-sestamibi uptake noted on breast scintigraphy, before to after neoadjuvant chemotherapy, may be used as an effective method for evaluating the response to neoadjuvant chemotherapy, since this quantification reflects the biological behavior of the tumor towards the chemotherapy regimen Furthermore, additional analysis on the uptake rate before chemotherapy may accurately predict treatment response

Feasibility of oncoplastic techniques in the surgical management of locally advanced breast cancer

Background: Locally advanced breast cancer (LABC) is still common in developing countries. The association between neoadjuvant chemotherapy (NC) and oncoplastic surgery (OS) might provide an oncological treatment with satisfactory aesthetic results.Purpose: The goal was to demonstrate if oncoplastic surgical techniques can be utilized to treat LABC which was submitted to neoadjuvant chemotherapy.Methods: This prospective clinical trial included breast cancer patients, clinical stage III, who underwent established NC regimen. All patients underwent preoperative planning to control the tumor size and to define the surgical technique. A detailed analysis of the pathological specimen was performed.Results: 50 patients were assessed and surgically treated. Tumor size ranged from 3.0 to 14.0 cm (median 6.5 cm). Pathologic response was rated as stable, progressive, partial response, and complete response in 10%, 8%, 80% and 2% of the cases, respectively. Seventeen (34%) patients were submitted to OS. No patient had positive margins. Skin involvement was presented in 36% of pathologic specimen.Conclusions: Oncoplastic surgical techniques for selected patients decrease the rates of radical surgery despite large tumors. (www.clinicaltrials.gov, NCT00820690). (C) 2012 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

Quality of life in women with vulvar cancer submitted to surgical treatment: a comparative study

Objectives: To investigate the occurrence and severity of lymphoedema of the lower extremities (LLE), quality of life (QoL), and urinary and sexual dysfunction in women with vulvar cancer submitted to surgical treatment.Study design: Twenty-eight patients with vulvar cancer submitted to vulvectomy and inguinofemoral lymphadenectomy and 28 healthy, age-matched women (control group) were evaluated. The occurrence and severity of LLE were determined by Miller's Clinical Evaluation. QoL, urinary function and sexual function were assessed by the EORTC QLQ-C30, SF-ICIQ and FSFI questionnaires, respectively. The differences between groups and correlations were assessed using Student's r-test, Chi-squared test, Mann-Whitney U-test and Spearman's rho test.Results: The groups were similar in terms of marital status, educational status, menopausal status, hormone therapy and height. The occurrence and severity of LLE were higher in women with vulvar cancer compared with the control group (p < 0.001 and p = 0.003, respectively). A significant association was found between the severity of LLE and advanced age (p = 0.04), and the severity of LLE and higher body mass index (BMI; p = 0.04) in patients with vulvar cancer. In the patients with vulvar cancer, there was a significant correlation between the severity of LLE and worse QoL in the following domains: physical, cognitive, emotional, social, fatigue, pain, sleep and financial questions (p < 0.05). There was no difference in urinary function between the two groups (p = 0.113). Age and number of deliveries were the only variables associated with the occurrence of urinary incontinence (p = 0.01). Urinary incontinence was present in women with a mean age of 74.9 +/- 4.6 years and a mean of 7.3 +/- 1.3 normal deliveries. There was no difference between the groups in terms of the sexual function. Multivariate analysis showed an association between sexual function and age (p = 0.01), and sexual function and being in a stable relationship (p = 0.02).Conclusion: Patients submitted to vulvectomy or inguinofemoral lymphadenectomy for vulvar cancer are at higher risk of developing LLE compared with healthy, age-matched women. This has a negative effect on QoL, but does not interfere with urinary or sexual function. (C) 2012 Elsevier B.V. All rights reserved.

Increased plasma and salivary cortisol levels in patients with oral cancer and their association with clinical stage

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Methylation profile of genes CDKN2A (p14 and p16), DAPK1, CDH1, and ADAM23 in head and neck cancer

Hypermethylation in the promoter region has been associated with a loss of gene function that may give a selective advantage to neoplastic cells. In this study, the methylation pattern of genes CDKN2A (alias p14, p14(ARF), p16, p16(INK4a)), DAPK1, CDH1, and ADAM23 was analyzed in 43 samples of head and neck tumors using methylation-specific polymerase chain reaction. In the oropharynx, there was a statistically significant association between hypermethylation of the DAPK1 gene and the occurrence of lymph node metastases, and in the larynx there was statistically significant evidence of an association between hypermethylation of the ADAM23 gene and advanced stages of the tumors. Thus, a correlation was observed between hypermethylation of the promoter region of genes DAPK1 and ADAM23 and the progression of head and neck cancer. (c) 2007 Elsevier B.V. All rights reserved.

Single testicular metastasis mimicking primary testicular neoplasm: A rare manifestation of prostate cancer

The incidence of secondary testicular tumors ranges from 0.02 to 2.5% among autopsies in general. With the exception of leukemias and lymphomas, prostate cancer is the most common primary site. It is diagnosed in autopsies or incidentally, following therapeutic orchiectomies in more advanced stages of the disease. In the present report, we show a case of testicular metastasis derived from prostate neoplasm whose clinical presentation as a single metastasis was similar to a primary testicular neoplasm. The diagnosis was evidenced after orchiectomy by histological examination and immunohistochemical tests.

Mesh cancer: long-term mesh infection leading to squamous-cell carcinoma of the abdominal wall

Purpose: It is recognized that chronic inflammation can cause cancer. Even though most of the available synthetic meshes are considered non-carcinogenic, the inflammatory response to an infected mesh plays a constant aggression to the skin. Chronic mesh infection is frequently the result of misuse of mesh, and due to the challenging nature of this condition, patients usually suffer for years until the infected mesh is removed by surgical excision. Methods: We report two cases of squamous-cell carcinoma (SCC) of the abdominal wall, arising in patients with long-term mesh infection. Results: In both patients, the degeneration of mesh infection into SCC was presumably caused by the long-term inflammation secondary to infection. Patients presented with advanced SCC behaving just like the Marjolin's ulcers of burns. Radical surgical excision was the treatment of choice. The involvement of the bowel played an additional challenge in case 1, but it was possible to resect the tumor and the involved bowel and reconstruct the abdominal wall using polypropylene mesh as onlay reinforcement, in a single stage operation. He is now under adjuvant chemotherapy. The big gap in the midline after tumor resection in case 2 required mesh bridging to close the defect. The poor prognosis of case 2 who died months after the operation, and the involvement of the armpit, groin and mesenteric nodes in case 1 shows how aggressive this disease can be. Conclusion: Infected mesh must be treated early, by complete excision of the mesh. Long-standing mesh infection can degenerate into aggressive squamous-cell carcinoma of the skin. © 2013 Springer-Verlag France.

A new proposed rodent model of chemically induced prostate carcinogenesis: Distinct time-course prostate cancer progression in the dorsolateral and ventral lobes

Background. Characterization of novel rodent models for prostate cancer studies requires evaluation of either spontaneous and carcinogen-induced tumors as well as tumor incidence in different prostatic lobes. We propose a new short-term rodent model of chemically induced prostate carcinogenesis in which prostate cancer progression occurs differentially in the dorsolateral and ventral lobes. Methods. Adult gerbils were treated with MNU alone or associated with testosterone for 3 or 6 months of treatment. Tumor incidence, latency, localization, and immunohistochemistry (AR, PCNA, smooth muscle α-actin, p63, MGMT, and E-cadherin) were studied in both lobes. Results. Comparisons between both lobes revealed that lesions developed first in the DL while the VL presented longer tumor latency. However, after 6 months, there was a dramatic increase in tumor multiplicity in the VL, mainly in MNU-treated groups. Lesions clearly progressed from a premalignant to a malignant phenotype over time and tumor latency was decreased by MNU + testosterone administration. Three-dimensional reconstruction of the prostatic complex showed that the DL developed tumors exclusively in the periurethral area and showed intense AR, PCNA, and MGMT immunostaining. Moreover, VL lesions emerged throughout the entire lobe. MNU-induced lesions presented markers indicative of an aggressive phenotype: lack of basal cells, rupture of the smooth muscle cell layer, loss of E-cadherin, and high MGMT staining. Conclusions. There are distinct pathways involved in tumor progression in gerbil prostate lobes. This animal provides a good model for prostate cancer since it allows the investigation of advanced steps of carcinogenesis with shorter latency periods in both lobes. Copyright © 2013 Wiley Periodicals, Inc.

TWIST1 Is a Molecular Marker for a Poor Prognosis in Oral Cancer and Represents a Potential Therapeutic Target

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)