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Tumor hypoxia may compromise the results of chemotherapy for treating colorectal cancer because it stimulates angiogenesis and the release of tumor growth factors. Hyperbaric oxygen (HBO) supplementation may potentiate the effects of chemotherapy in such cases. This study aimed to assess the effect of HBO therapy combined with chemotherapy on the treatment of colorectal cancer in mice. C57BL6 mice were submitted to the intrarectal instillation of N-methyl-N-nitrosoguanidine (MNNG) and treated with 5-fluorouracil (5FU) and/or HBO therapy. The MNNG group presented the highest dysplastic crypt rate. The 5FU + HBO group presented the highest rate of apoptotic cells per dysplastic crypt. The 5FU group presented the highest expression of hypoxia-inducible factor-1 alpha and CD44. HBO therapy increased the effect of 5FU on the treatment of the experimental colorectal neoplasia in mice.

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BACKGROUND AND OBJECTIVE: Current studies based on digital biopsy images have achieved satisfactory results in detecting colon cancer despite their limited visual spectral range. Such methods may be less accurate when applied to samples taken from the tumor margin region or to samples containing multiple diagnoses. In contrast with the traditional computer vision approach, micro-FTIR hyperspectral images quantify the tissue-light interaction on a histochemical level and characterize different tissue pathologies, as they present a unique spectral signature. Therefore, this paper investigates the possibility of using hyperspectral images acquired over micro-FTIR absorbance spectroscopy to characterize healthy, inflammatory, and tumor colon tissues. METHODS: The proposed method consists of modeling hyperspectral data into a voxel format to detect the patterns of each voxel using fully connected deep neural network. A web-based computer-aided diagnosis tool for inference is also provided. RESULTS: Our experiments were performed using the K-fold cross-validation protocol in an intrapatient approach and achieved an overall accuracy of 99% using a deep neural network and 96% using a linear support vector machine. Through the experiments, we noticed the high performance of the method in characterizing such tissues using deep learning and hyperspectral images, indicating that the infrared spectrum contains relevant information and can be used to assist pathologists during the diagnostic process.

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BACKGROUND: Colorectal cancer (CRC) has a high mortality rate and can develop in either colitis-dependent (colitis-associated (CA)-CRC) or colitis-independent (sporadic (s)CRC) manner. There has been a significant debate about whether mast cells (MCs) promote or inhibit the development of CRC. Herein we investigated MC activity throughout the multistepped development of CRC in both human patients and animal models. METHODS: We analyzed human patient matched samples of healthy colon vs CRC tissue alongside conducting a The Cancer Genome Atlas-based immunogenomic analysis and multiple experiments employing genetically engineered mouse (GEM) models. RESULTS: Analyzing human CRC samples revealed that MCs can be active or inactive in this disease. An activated MC population decreased the number of tumor-residing CD8 T cells. In mice, MC deficiency decreased the development of CA-CRC lesions, while it increased the density of tumor-based CD8 infiltration. Furthermore, co-culture experiments revealed that tumor-primed MCs promote apoptosis in CRC cells. In MC-deficient mice, we found that MCs inhibited the development of sCRC lesions. Further exploration of this with several GEM models confirmed that different immune responses alter and are altered by MC activity, which directly alters colon tumorigenesis. Since rescuing MC activity with bone marrow transplantation in MC-deficient mice or pharmacologically inhibiting MC effects impacts the development of sCRC lesions, we explored its therapeutic potential against CRC. MC activity promoted CRC cell engraftment by inhibiting CD8+ cell infiltration in tumors, pharmacologically blocking it inhibits the ability of allograft tumors to develop. This therapeutic strategy potentiated the cytotoxic activity of fluorouracil chemotherapy. CONCLUSION: Therefore, we suggest that MCs have a dual role throughout CRC development and are potential druggable targets against this disease.

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Background and purpose: The discovery of chemical substances with carcinogenic properties has allowed the development of several experimental models of colorectal cancer (CRC). Classically, experimental models of CRC in mice have been evaluated through clinical or serial euthanasia. The present study aims to investigate the role of low endoscopy in the analysis of carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Methods: Thirty C57BL6 mice were divided into two groups: a control group with fifteen animals that underwent rectal instillation of saline solution on day 0 and a carcinogen group with fifteen animals that underwent a 100 mg/kg MNNG rectal instillation on day 0. In both groups, low endoscopies were performed on weeks 4 and 8. We used a validated endoscopic scoring system to evaluate the severity of colitis and colorectal tumor. Euthanasia was carried out at week 12. Results: We observed higher inflammation scores (p <0.001) and a higher number of tumors (p <0.05) in the MNNG group than the control group, both at weeks 4 and 8. A worsening of inflammation scores from the first to the second endoscopy was also noticeable in the MNNG group. There were no bowel perforations related to the procedure, and there was one death in the control group. Conclusion: Low endoscopy in experimental animals allows safe macroscopic evaluation of colorectal carcinogenesis without the need for euthanasia.

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OBJECTIVE: To analyze the effect of thalidomide on the progression of endometriotic lesions experimentally induced in rats and to characterize the pattern of cell proliferation by immunohistochemical Proliferating Cell Nuclear Antigen (PCNA) labeling of eutopic and ectopic endometrium. METHODS: Fifteen female Wistar rats underwent laparotomy for endometriosis induction by resection of one uterine horn, isolation of the endometrium and fixation of a tissue segment to the pelvic peritoneum. Four weeks after, the animals were divided into 3 groups: control (I), 10mg/kg/day (II) and 1mg/kg/day (III) intraperitoneal thalidomide for 10 days. The lesion was excised together with the opposite uterine horn for endometrial gland and stroma analysis. Eutopic and ectopic endometrial tissue was submitted to immunohistochemistry for analysis of cell proliferation by PCNA labeling and the cell proliferation index (CPI) was calculated as the number of labeled cells per 1,000 cells. RESULTS: Group I showed a mean CPI of 0.248 ± 0.0513 in the gland and of 0.178 ± 0.046 in the stroma. In contrast, Groups II and III showed a significantly lower CPI, that is, 0.088 ± 0.009 and 0.080 ± 0.021 for the gland (p < 0.001) and 0.0945 ± 0.0066 and 0.075 ± 0.018 for the stroma (p < 0.001), respectively. Also, the mean lesion area of Group I was 69.2 mm2, a significantly higher value compared with Group II (49.4 mm2, p = 0.023) and Group III (48.6 mm2, p = 0.006). No significant difference was observed between Groups II and III. CONCLUSION: Thalidomide proved to be effective in reducing the lesion area and CPI of the experimental endometriosis implants both at the dose of 1 mg/kg/day and at the dose of 10 mg/kg/day.

OBJETIVO: Analisar o efeito da talidomida na progressão de lesões endometrióticas induzidas experimentalmente em ratas e caracterizar o padrão de proliferação celular pela marcação imunohistoquímica de Antígeno Nuclear de Célula Proliferativa (PCNA) no endométrio eutópico e ectópico. MéTODOS: Quinze ratas Wistar foram submetidas a laparotomia para indução de endometriose por ressecção de um corno uterino, isolamento do endométrio e fixação de um segmento do tecido ao peritônio pélvico. Após quatro semanas, os animais foram divididos em 3 grupos: controle (I), 10 mg/kg/dia (II) e 1 mg/kg/dia (III) de talidomida intraperitoneal por um período de 10 dias. As lesões foram resseccionadas juntamente com o corno uterino oposto para análise da glândula endometrial e do estroma. O tecido endometrial eutópico e ectópico foi submetido à imunohistoquímica para análise da proliferação celular por marcação com PCNA e o índice de proliferação celular (CPI) foi calculado como o número de células marcadas por 1.000 células. RESULTADOS: O grupo I apresentou média de CPI de 0,248 ± 0,0513 na glândula e de 0,178 ± 0,046 no estroma. Em contraste, os grupos II e III apresentaram CPI significativamente menor, isto é, 0,088 ± 0,009 e 0,080 ± 0,021 para a glândula (p < 0,001) e 0,0945 ± 0,0066 e 0,075 ± 0,018 para o estroma (p < 0,001), respectivamente. Além disso, a área de lesão média do Grupo I foi de 69,2 mm2, valor significativamente maior em relação ao Grupo II (49,4 mm2, p = 0,023) e Grupo III (48,6 mm2, p = 0,006). Não houve diferença estatisticamente significante entre os Grupos II e III. CONCLUSãO: A talidomida mostrou-se eficaz na redução da área da lesão e CPI dos implantes de endometriose experimental tanto na dose de 1 mg/kg/dia quanto na dose de 10 mg/kg/dia.

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Abstract Objective To analyze the effect of thalidomide on the progression of endometriotic lesions experimentally induced in rats and to characterize the pattern of cell proliferation by immunohistochemical Proliferating Cell Nuclear Antigen (PCNA) labeling of eutopic and ectopic endometrium. Methods Fifteen female Wistar rats underwent laparotomy for endometriosis induction by resection of one uterine horn, isolation of the endometrium and fixation of a tissue segment to the pelvic peritoneum. Four weeks after, the animals were divided into 3 groups: control (I), 10mg/kg/day (II) and 1mg/kg/day (III) intraperitoneal thalidomide for 10 days. The lesion was excised together with the opposite uterine horn for endometrial gland and stroma analysis. Eutopic and ectopic endometrial tissue was submitted to immunohistochemistry for analysis of cell proliferation by PCNA labeling and the cell proliferation index (CPI) was calculated as the number of labeled cells per 1,000 cells. Results Group I showed a mean CPI of 0.248 ± 0.0513 in the gland and of 0.178 ± 0.046 in the stroma. In contrast, Groups II and III showed a significantly lower CPI, that is, 0.088 ± 0.009 and 0.080 ± 0.021 for the gland (p < 0.001) and 0.0945 ± 0.0066 and 0.075 ± 0.018 for the stroma (p < 0.001), respectively. Also, the mean lesion area of Group I was 69.2mm2, a significantly higher value compared with Group II (49.4mm2, p = 0.023) and Group III (48.6mm2, p = 0.006). No significant difference was observed between Groups II and III. Conclusion Thalidomide proved to be effective in reducing the lesion area and CPI of the experimental endometriosis implants both at the dose of 1mg/kg/day and at the dose of 10 mg/kg/day.

Resumo Objetivo Analisar o efeito da talidomida na progressão de lesões endometrióticas induzidas experimentalmente em ratas e caracterizar o padrão de proliferação celular pela marcação imunohistoquímica de Antígeno Nuclear de Célula Proliferativa (PCNA) no endométrio eutópico e ectópico. Métodos Quinze ratas Wistar foram submetidas a laparotomia para indução de endometriose por ressecção de um corno uterino, isolamento do endométrio e fixação de um segmento do tecido ao peritônio pélvico. Após quatro semanas, os animais foram divididos em 3 grupos: controle (I), 10 mg/kg/dia (II) e 1 mg/kg/dia (III) de talidomida intraperitoneal por um período de 10 dias. As lesões foram resseccionadas juntamente com o corno uterino oposto para análise da glândula endometrial e do estroma. O tecido endometrial eutópico e ectópico foi submetido à imunohistoquímica para análise da proliferação celular por marcação com PCNA e o índice de proliferação celular (CPI) foi calculado como o número de células marcadas por 1.000 células. Resultados O grupo I apresentou média de CPI de 0,248 ± 0,0513 na glândula e de 0,178 ± 0,046 no estroma. Em contraste, os grupos II e III apresentaram CPI significativamentemenor, isto é, 0,088 ± 0,009 e 0,080 ± 0,021 para a glândula (p < 0,001) e 0,0945 ± 0,0066 e 0,075 ± 0,018 para o estroma (p < 0,001), respectivamente. Além disso, a área de lesãomédia do Grupo I foi de 69,2mm2, valor significativamentemaior em relação ao Grupo II (49,4mm2, p = 0,023) e Grupo III (48,6mm2, p = 0,006). Não houve diferença estatisticamente significante entre os Grupos II e III. Conclusão A talidomida mostrou-se eficaz na redução da área da lesão e CPI dos implantes de endometriose experimental tanto na dose de 1mg/kg/dia quanto na dose de 10 mg/kg/dia.

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PURPOSE: The denervation of the intestine with benzalkonium chloride (BAC) reduces mortality and improves weight gain in rats with short bowel syndrome (SBS). Nevertheless, translating these promising findings from bench to bedside is not feasible because BAC promotes peritonitis and irreversible denervation which may be followed by an uncontrolled dilatation of the viscera. The use of botulinum toxin (BT) instead of BAC to achieve the denervation of the remaining small intestine in SBS could be an interesting option because it leads to a mild and transient denervation of the intestine. METHODS: Here we evaluated the effects of the ileal denervation with BT in rats with SBS by verifying the body weight variation and intestinal morphological parameters. Four groups with 6 animals each were submitted to enterectomy with an ileal injection of saline (group E) or BT (group EBT). Control groups were submitted to simulated surgery with an ileal injection of BT (group BT) or saline (group C - control). RESULTS: We observed that the treatment of the remaining ileum with BT completely reversed the weight loss associated to extensive small bowel resection. CONCLUSION: This may provide a new promising approach to the surgical treatment of SBS.

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Purpose: The denervation of the intestine with benzalkonium chloride (BAC) reduces mortality and improves weight gain in rats with short bowel syndrome (SBS). Nevertheless, translating these promising findings from bench to bedside is not feasible because BAC promotes peritonitis and irreversible denervation which may be followed by an uncontrolled dilatation of the viscera. The use of botulinum toxin (BT) instead of BAC to achieve the denervation of the remaining small intestine in SBS could be an interesting option because it leads to a mild and transient denervation of the intestine. Methods: Here we evaluated the effects of the ileal denervation with BT in rats with SBS by verifying the body weight variation and intestinal morphological parameters. Four groups with 6 animals each were submitted to enterectomy with an ileal injection of saline (group E) or BT (group EBT). Control groups were submitted to simulated surgery with an ileal injection of BT (group BT) or saline (group C control). Results: We observed that the treatment of the remaining ileum with BT completely reversed the weight loss associated to extensive small bowel resection. Conclusion: This may provide a new promising approach to the surgical treatment of SBS.(AU)

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OBJECTIVE: The aim of this study was to evaluate the impact of High Voltage Pulsed Current (HVPC) on the integration of total skin grafts in rats submitted to nicotine action. MATERIALS AND METHODS: For this purpose, 60 adult Wistar rats randomly distributed in 6 groups of 10 animals were analyzed. The electrical stimulation (anodic and cathodic stimulation, motor level, 30 min at 10 Hz; minimum voltage 20 µs and 100 µs pulse interval) was applied for seven days, starting on the third day after surgery and after the dressing was removed from the graft. RESULTS: Anodic HVPC promoted greater graft integration, demonstrating a lower percentage of tissue contraction, a lower number of inflammatory infiltrates and a greater amount of vascular endothelial growth factor (VEGF), as well as a higher number of newly formed blood vessels. CONCLUSIONS: HVPC can positively influence the integration of skin grafts in nicotine-treated rats. anodic HVPC is shown to promote greater integration in relation to a lower percentage of tissue contraction, a lower number of inflammatory infiltrates and a greater amount of vascular endothelial growth factor and newformed blood vessels. Whereas, the cathodic polarity has presented smaller amount of tissue gap.

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Experimental denervation of organs plays a key role in understanding the functional aspects of the normal innervation as well as the diseases related to them. In 1978 the experimental model of myenteric denervation of the rat gut by serosal application of benzalkonium chloride (BAC) was proposed. BAC is a positively charged surface-active alkylamine and is a powerful cationic detergent, which destroys bacteria after ionic attraction and for this reason is largely used as a surgical antiseptic. Since its initial report, the BAC-induced myenteric denervation model has been used to study many functional and pathological aspects of the enteric nervous system. So far this is the only pure method of myenteric denervation available for research in this area. Promising reports in the literature have shed light on the possibilities for the development of new uses of the BAC-denervation experimental model as a therapeutic tool in some pathological situations. This review aims to shed light on the main historical and recent findings provided by this experimental model.

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