Survival and prognostic factors in patients with oral squamous cell carcinoma.

BACKGROUND: This study aimed to evaluate sociodemographic and clinical factors influencing overall survival (OS) in patients with oral squamous cell carcinoma (OSCC). MATERIAL AND METHODS: Medical charts of 547 patients with OSCC from a public hospital in northeastern Brazil seen between 1999 and 2013 were evaluated. Survival analysis was performed using the Kaplan-Meier method. The influence of age, sex, ethnicity, clinical stage, anatomical location, type of treatment, and comorbidities on the patients' prognosis was evaluated. Cox proportional hazards regression model was used to identify independent prognostic factors. RESULTS: The 5-year OS was 39%. Multivariate analysis showed that age < 40 years (HR = 2.20; 95%CI: 1.02-4.72) and a single treatment modality (HR = 1.91; 95%CI: 1.37-2.67) were associated with a poor prognosis, while early clinical stage resulted in better outcomes (HR = 0.38; 95%CI: 0.25-0.58). CONCLUSIONS: OSCC patients in advanced clinical stages, diagnosed at a younger age, and submitted to a single therapeutic modality have a poorer prognosis.

Benzofuroxan derivatives N-Br and N-I induce intrinsic apoptosis in melanoma cells by regulating AKT/BIM signaling and display anti metastatic activity in vivo.

BACKGROUND: Malignant melanoma is an aggressive type of skin cancer, and despite recent advances in treatment, the survival rate of the metastatic form remains low. Nifuroxazide analogues are drugs based on the substitution of the nitrofuran group by benzofuroxan, in view of the pharmacophore similarity of the nitro group, improving bioavailability, with higher intrinsic activity and less toxicity. Benzofuroxan activity involves the intracellular production of free-radical species. In the present work, we evaluated the antitumor effects of different benzofuroxan derivatives in a murine melanoma model. METHODS: B16F10-Nex2 melanoma cells were used to investigate the antitumor effects of Benzofuroxan derivatives in vitro and in a syngeneic melanoma model in C57Bl/6 mice. Cytotoxicity, morphological changes and reactive oxygen species (ROS) were assessed by a diphenyltetrasolium reagent, optical and fluorescence microscopy, respectively. Annexin-V binding and mitochondrial integrity were analyzed by flow cytometry. Western blotting and colorimetry identified cell signaling proteins. RESULTS: Benzofuroxan N-Br and N-I derivatives were active against murine and human tumor cell lines, exerting significant protection against metastatic melanoma in a syngeneic model. N-Br and N-I induce apoptosis in melanoma cells, evidenced by specific morphological changes, DNA condensation and degradation, and phosphatidylserine translocation in the plasma membrane. The intrinsic mitochondrial pathway in B16F10-Nex2 cells is suggested owing to reduced outer membrane potential in mitochondria, followed by caspase -9, -3 activation and cleavage of PARP. The cytotoxicity of N-Br and N-I in B16F10-Nex2 cells is mediated by the generation of ROS, inhibited by pre-incubation of the cells with N-acetylcysteine (NAC). The induction of ROS by N-Br and N-I resulted in the inhibition of AKT activation, an important molecule related to tumor cell survival, followed by upregulation of BIM. CONCLUSION: We conclude that N-Br and N-I are promising agents aiming at cancer treatment. They may be useful in melanoma therapy as inducers of intrinsic apoptosis and by exerting significant antitumor activity against metastatic melanoma, as presently shown in syngeneic mice.

Synthetic phosphoethanolamine has in vitro and in vivo anti-leukemia effects.

BACKGROUND: We recently showed that synthetic phosphoethanolamine reduces tumour growth and inhibits lung metastasis in vivo. Here, we investigated its anti-leukaemia effects using acute promyelocytic leukaemia (APL) as a model. METHODS: Cytotoxic effects of Pho-s on leukaemia cells were evaluated by MTT assay. Leukaemic cells obtained from hCG-PML-RARa transgenic mice were transplanted to NOD/SCID mice. After the animals were diagnosed as leukaemic, treatment started with Pho-s using all-trans retinoid acid or daunorubicin as positive control or and saline control. Cell morphology and immunophenotyping were used to detect the undifferentiated blast cells in the spleen, liver and bone marrow. The induction of apoptosis in vitro and in malignant leukaemic clones was evaluated. RESULTS: Synthetic phosphoethanolamine is cytotoxic and induces apoptosis through the mitochondrial pathway in vitro to leukaemia cell lines. In vivo Pho-s exhibits anti-proliferative effects in APL model reducing the number of CD117(+) and Gr-1(+) immature myeloid cells in the BM, spleen and liver. Synthetic phosphoethanolamine impairs the expansion of malignant clones CD34(+)/CD117(+), CD34(+) and Gr-1(+) in the BM. In addition, Pho-s induces apoptosis of immature cells in the spleen and liver, a notable effect. CONCLUSION: Synthetic phosphoethanolamine has anti-leukaemic effects in an APL model by inhibiting malignant clone expansion, suggesting that it is an interesting compound for leukaemia treatment.

Involvement of formyl peptide receptors in the stimulatory effect of crotoxin on macrophages co-cultivated with tumour cells.

Crotoxin (CTX) is the main neurotoxic component of Crotalus durissus terrificus snake venom. It inhibits tumour growth and modulates the function of macrophages, which are essential cells in the tumour microenvironment. The present study investigated the effect of CTX on the secretory activity of monocultured macrophages and macrophages co-cultivated with LLC-WRC 256 cells. The effect of the macrophage secretory activities on tumour cell proliferation was also evaluated. Macrophages pre-treated with CTX (0.3 µg/mL) for 2 h were co-cultivated with LLC-WRC 256 cells, and the secretory activity of the macrophages was determined after 12, 24 and 48 h. The co-cultivation of CTX-treated macrophages with the tumour cells caused a 20% reduction in tumour cell proliferation. The production of both H2O2 and NO was increased by 41% and 29% after 24 or 48 h of co-cultivation, respectively, compared to the values for the co-cultures of macrophages of control. The level of secreted IL-1ß increased by 3.7- and 3.2-fold after 12 h and 24 h of co-cultivation, respectively. Moreover, an increased level of LXA4 (25%) was observed after 24 h of co-cultivation, and a 2.3- and 2.1-fold increased level of 15-epi-LXA4 was observed after 24 h and 48 h, respectively. Boc-2, a selective antagonist of formyl peptide receptors, blocked both the stimulatory effect of CTX on the macrophage secretory activity and the inhibitory effect of these cells on tumour cell proliferation. Taken together, these results indicate that CTX enhanced the secretory activity of macrophages, which may contribute to the antitumour activity of these cells, and that activation of formyl peptide receptors appears to play a major role in this effect.

Persistencia del collar venoso renal / Persistence of renal venous collar

El desarrollo del sistema venoso cava es bastante complejo, pudiendo producirse innumerables variaciones de los padrones anatómicos ya conocidos, siendo algunos más frecuentes y otros de rara incidencia. De estas variaciones, puede ocurrir una en que se forma un anillo vascular en torno de la aorta, constituído por una vena renal pre-aórtica y otra retro-aórtica, desembocando a un nivel más bajo en la vena cava inferior (VCI), una disposición llamada "collar venoso renal", que consiste en la persistencia de las anastomosis intersupracardinales e intersubcardinales embrionarias. En la variación presentada en este artículo, la disposición de los vasos corresponde a un tipo de la clasificación mencionada en la literatura, con excepción de la emergencia independiente de los componentes pre y retroaórtico del collar referido, a partir del hilio renal y del calibre distal de la vena renal retroaórtica. La vena renal preaórtica tenía 90 mm de longitud y 20 mm de calibre en su parte terminal, desembocando en la VCI a nivel del tercio inferior de la vértebra L1. La vena renal retroaórtica tenía 125 mm de longitud, cruzando las vértebras L1 y L2 para desembocar en la VCI a nivel del tercio superior de L3, donde se registró un diámetro terminal de 14 mm. La disposición presentada, es una variación potencialmente peligrosa de la vena renal izquierda, importante de recalcar su presencia, ya que ha sido relatado que en cirugías retroperitoneales no se ha identificado el componente dorsal, produciendo hemorragia profusa, nefrectomía innecesaria y hasta la muerte.

The development of the cava venous system is very complex, taking place to the raising of innumerous variations of the anatomical patterns already known, which could be more or less common and others, still, of rare incidence. One of these anomalies may occur in a low frequency on the left side, forming a vascular ring around the aorta constituted by a preaortic renal vein and other retro-aortic renal vein, entering in a lower level of the VCI, in a condition called as " Renal Collar" consisted of persistence of the Intersupracardial embrionary anastomoses. In this case report, the vascular disposition corresponds to a type of the classification as related in literature, with exception of the independent emergency of the preaortic and retro-aortic components of the circum-aortic collar from the renal hilum and the distal diameter of the retroaortic renal vein. The preaortic vein had 90 mm of length, diameter of 20 mm in its end and led into the VCI on the lower level of L1. The retroaortic vein measured 125 mm of length, crossing L1 and L2 to discharge in the VCI, to the upper level of L3, where it had diameter of 14 mm. The importance of the study and description of the circumaortic renal collar is due to it representing a potentially hazardous anomaly of the left renal vein, occurring case reports where failure to recognize the dorsal component during retroperitoneal surgery may lead to abundant hemorrhage after inadvertent injury, unnecessary nephrectomy or, even death.

Mutagenic potential and modulatory effects of the medicinal plant Luehea divaricata (Malvaceae) in somatic cells of Drosophila melanogaster: SMART/wing.

Luehea divaricata is a native plant of the Brazilian Cerrado, known as "açoita-cavalo". It is used as a popular herbal medicine in the treatment of dysentery, bleeding, arthritis, tumors, ulcers, and gangrenous wounds. Considering that herbal medicines sometimes provoke tumors and/or may prevent mutational events, it is important to study the action of these natural drugs on DNA. Aqueous extract of the bark of L. divaricata was evaluated at three different concentrations (0.10, 0.30, 0.50 mg/mL), individually and in combination with the neoplastic drug doxorubicin (DXR), by the somatic mutation and recombination test (SMART/wing) in Drosophila melanogaster. Distilled water was included as a negative control. The mutation frequency in the treatments with L. divaricata extract alone was not significantly higher than in the negative control for standard (ST) and high bioactivation (HB) crosses. When L. divaricata extract was combined with DXR, there was a significant reduction in the frequency of spots when compared to DXR alone, in both crosses. Further studies with other experimental models would be useful to confirm that L. divaricata extract is not harmful and that it could be used in the prevention of cancer.

[Iatrogenic pneumothorax caused by acupuncture]. / Pneumotórax iatrogênico por acunputura.

A 68 year-old white male patient with previous diagnosis of pulmonary emphysema was submitted to acupuncture. The needles were inserted into the precordial area and the patient immediately complained of worsening dyspnea. Four days later pneumothorax was detected by chest X-rays. A thoracic tube was inserted with total lung expansion.

[Bronchodilation induced by fenoterol in asthmatic patients: comparison of jet nebulization and spacer device]. / Broncodilatação induzida pelo fenoterol em asmáticos: comparação entre nebulizador a jato e espaçador.

OBJECTIVE: To compare bronchodilation attained by fenoterol administered through a jet nebulizer and through a spacer device. TYPE OF STUDY: Open, randomized. PATIENTS: 44 adults with asthma, peak-flow rate varying between 120 and 200 l/min. Patients were divided into two groups. TREATMENT [corrected]: Group A was treated with fenoterol (2.5 mg) with saline to complete 3 ml given through a jet nebulizer; 30 minutes later, an additional dose (1 mg) was given through a 500 ml spacer. Group B was treated with the same dosage, but the spacer [corrected] was used first. EVALUATION: Peak-flow meter in zero, 30 and 60 minutes. RESULTS: No significant difference in bronchodilation was seen between groups A and B. CONCLUSION: Fenoterol through a spacer can replace inhalation in adult asthma patients with non-severe obstruction. Lower cost and home treatment are the main advantages.