Curcumin,its derivatives,and their nanoformulations: Revolutionizing cancer treatment

Curcumin is a natural compound derived from turmeric and can target malignant tumor molecules involved in cancer propagation. It has potent antioxidant activity, but its effectiveness is limited due to poor absorption and rapid elimination from the body. Various curcumin derivatives have also shown anticancer potential in in-vitro and in-vivo models. Curcumin can target multiple signaling pathways involved in cancer development/progression or induce cancer cell death through apoptosis. In addition, curcumin and its derivatives could also enhance the effectiveness of conventional chemotherapy, radiation therapy and reduce their associated side effects. Lately, nanoparticle-based delivery systems are being developed/explored to overcome the challenges associated with curcumin's delivery, increasing its overall efficacy. The use of an imaging system to track these formulations could also give beneficial information about the bioavailability and distribution of the nano-curcumin complex. In conclusion, curcumin holds significant promise in the fight against cancer, especially in its nanoform, and could provide precise delivery to cancer cells without affecting normal healthy cells.     

Cellular and subcellular localization of gastrointestinal glutathione peroxidase in normal and malignant human intestinal tissue

The gastrointestinal glutathione peroxidase (GI-GPx) is believed to prevent absorption of hydroperoxides. GI-GPx is expressed in the intestine together with the other three glutathione peroxidase isoenzymes, raising the question of the physiological role of the different GPx types. We therefore studied the cellular and subcellular distribution of GI-GPx in normal and malignant tissue obtained from patients with colorectal cancer or familial polyposis by immunohistochemistry. In healthy ileum epithelium GI-GPx was preferentially enriched in Paneth cells. In unaffected crypts of colon and rectum, it decreased gradually from the ground to the luminal surface. In crypt ground, GI-GPx was uniformly distributed, whereas in cells at the luminal surface it was concentrated in structures capping the nuclei at the apical pole. In colorectal cancer, GI-GPx expression depended on the stage of malignant transformation. In early stages, GI-GPx was increased and pronouncedly associated with the vesicular structures. In progressed stages of malignancy, structures disintegrated and GI-GPx distribution became more diffuse. These observations support the hypothesis that GI-GPx, apart from being a barrier against hydroperoxide absorption, might be involved in cell growth and differentiation.     

Cellular and subcellular localization of gastrointestinal glutathione peroxidase in normal and malignant human intestinal tissue

The gastrointestinal glutathione peroxidase (GI-GPx) is believed to prevent absorption of hydroperoxides. GI-GPx is expressed in the intestine together with the other three glutathione peroxidase isoenzymes, raising the question of the physiological role of the different GPx types. We therefore studied the cellular and subcellular distribution of GI-GPx in normal and malignant tissue obtained from patients with colorectal cancer or familial polyposis by immunohistochemistry. In healthy ileum epithelium GI-GPx was preferentially enriched in Paneth cells. In unaffected crypts of colon and rectum, it decreased gradually from the ground to the luminal surface. In crypt ground, GI-GPx was uniformly distributed, whereas in cells at the luminal surface it was concentrated in structures capping the nuclei at the apical pole. In colorectal cancer, GI-GPx expression depended on the stage of malignant transformation. In early stages, GI-GPx was increased and pronouncedly associated with the vesicular structures. In progressed stages of malignancy, structures disintegrated and GI-GPx distribution became more diffuse. These observations support the hypothesis that GI-GPx, apart from being a barrier against hydroperoxide absorption, might be involved in cell growth and differentiation.     

大肠埃希菌在肿瘤患者肠外的分布及耐药谱分析

目的：了解大肠埃希菌在肿瘤患者肠外的分布和感染情况及耐药性。方法：参照全国临床检验操作规程,采用K-B法对云南省肿瘤医院58例肿瘤患者继发大肠埃希菌感染进行分析及对9种抗生素的耐药谱测定。结果：各类肿瘤患者中,以宫颈癌及继发大肠埃希菌感染多见,其中,宫颈癌为28.30%。肺癌为26.87%。从标本来源来看,以尿液标本最多,为63.79%,其次为痰液12.07%及分泌物12.07%。结论：大肠埃希菌在肿瘤患者肠外分布广泛,所致感染较严重,经耐药谱测定发现大肠埃希菌多重耐药类型多,提示对肿瘤患者治疗应重视局部微生态平衡及控制感染。     

Tenascin distribution in the normal human breast is altered during the menstrual cycle and in carcinoma

Tenascin is a novel extracellular matrix glycoprotein which appears to have a major role in tissue development. Previous studies have stated that tenascin is absent from the normal human, rat and mouse breast, its distribution being restricted to embryonic and malignant mammary tissues. No previous studies have investigated tenascin distribution as a function of the normal menstrual cycle. Therefore this study addresses the cyclical appearance of tenascin in the normal breast and associated changes in distribution in preinvasive cancer (carcinoma-in-situ) and invasive infiltrating ductal carcinoma. Tenascin is present in the normal human adult mammary gland, principally in the basement membrane, sub-basement-membrane zone and delimiting layer of fibroblasts around the ductules. Both the distribution and quantity of tenascin change during the menstrual cycle. In carcinoma-in-situ (preinvasive cancer) tenascin is present in the attenuated basement membrane/sub-basement-membrane zone around the expanded ductules and in small amounts in the stroma. In infiltrating ductal carcinoma, tenascin is absent from the remnants of the basement membrane and sub-basement-membrane zone but greatly increased in the adjacent intralobular and interlobular stroma. Therefore, if tenascin is used as a basement membrane/sub-basement-membrane marker for distinguishing carcinoma-in-situ from invasive ductal carcinoma, the time of the menstrual cycle is of importance in interpreting the biopsy appearance. This study suggests that the optimal time for biopsy is between weeks 3 and 4 of the cycle, to avoid confusion between the normal low levels of tenascin (due to hormonal status) and those due to microinvasive disease.(ABSTRACT TRUNCATED AT 250 WORDS)     

RKIP Inhibition in Cervical Cancer Is Associated with Higher Tumor Aggressive Behavior and Resistance to Cisplatin Therapy

Cervical cancer is one of the most common cancers in women worldwide, being high-risk group the HPV infected, the leading etiological factor. The raf kinase inhibitory protein (RKIP) has been associated with tumor progression and metastasis in several human neoplasms, however its role on cervical cancer is unclear. In the present study, 259 uterine cervix tissues, including cervicitis, cervical intraepithelial lesions and carcinomas, were analyzed for RKIP expression by immunohistochemistry. We found that RKIP expression was significantly decreased during malignant progression, being highly expressed in non-neoplastic tissues (54% of the samples; 73/135), and expressed at low levels in the cervix invasive carcinomas (∼15% (19/124). Following in vitro downregulation of RKIP, we observed a viability and proliferative advantage of RKIP-inhibited cells over time, which was associated with an altered cell cycle distribution and higher colony number in a colony formation assay. An in vitro wound healing assay showed that RKIP abrogation is associated with increased migratory capability. RKIP downregulation was also associated with an increased vascularization of the tumors in vivo using a CAM assay. Furthermore, RKIP inhibition induced cervical cancer cells apoptotic resistance to cisplatin treatment. In conclusion, we described that RKIP protein is significantly depleted during the malignant progression of cervical tumors. Despite the lack of association with patient clinical outcome, we demonstrate, in vitro and in vivo, that loss of RKIP expression can be one of the factors that are behind the aggressiveness, malignant progression and chemotherapy resistance of cervical cancer.     

Cancer gene therapy – state-of-the-art

A number of gene therapy clinical trials are being carried out the world over. Gene therapy is being applied in (I) cancer diseases, involving the largest number of patients, (II) monogenic diseases, (III) infectious diseases, (IV) vascular diseases, (V) autoimmune diseases and others. In the last decade, several strategies of cancer gene therapy have emerged due to a rapid development of gene delivery systems, both viral (recombinant retroviruses, adenoviruses, AAVs, herpes viruses) and nonviral (liposomes, gene guns, electroporation). To date four main strategies of cancer gene therapy have been evaluated in clinical trials: (I) immunogene therapy, (II) suicide gene therapy, (III) antiangiogenic gene therapy, (IV) and administration of tumour suppressor genes.These strategies mostly involve: malignant melanoma, prostate cancer, renal cell cancer, colon cancer, breast and ovarian cancers, lung cancers, neoplastic diseases of the blood and brain tumours.At the Department of Cancer Immunology at the GreatPoland Cancer Center Gene Modified Tumour Vaccine has been tested in malignant melanoma patients for more than six years. Due to encouraging results from phase I and II of clinical trials a phase III was designed and will be started in 2003.     

Trends in mortality from primary tumours of skin in Canada

In Canada the death rate from all primary malignant neoplasms of skin has remained approximately stable since the early 1950s. The rates have fallen in those over age 65 and risen in those aged 45 to 64 and 15 to 44. We have no reason to believe that this is due to a change in certification or to a deterioration in treatment. The rise has been wholly due to a doubling in the death rate from malignant melanoma. This is in agreement with the trend of Canadian incidence data and with the experience of other developed countries. We are of the opinion that this change is largely due to a genuine increase in the incidence of malignant melanoma.     

Proprotein convertases blockage up-regulates specifically metallothioneins coding genes in human colon cancer stem cells

Despite continuous exertion made, colon cancer still represents a major health problem and its incidence continues being high worldwide. There is growing evidence in support of the cancer stem cells (CSCs) being central in the initiation of this cancer, and CSCs have been the focus of various studies for the identification of new ways of treatment. Lately, the proprotein convertases (PCs) were reported to regulate the maturation and expression of various molecules involved in the malignant phenotype of colon cancer cells, however, the identity of the molecules regulated by these serine proteases in CSCs is unknown. In this study, we used the general PCs inhibitor, the Decanoyl-RVKR-chloromethylketone (Decanoyl-RVKR-CMK) that inhibits all the PCs found in the secretory pathway, and analyzed its effect on CSCs using RNA-seq analysis. Remarkably, from the only 9 up-regulated genes in the human SW620-derived sphere-forming cells, we identified 7 of the 11 human metallothioneins, all of them localized on chromosome 16, and zinc related proteins as downstream effectors of the PCs. The importance of these molecules in the regulation of cell proliferation, differentiation and chemoresistance, and their reported potential tumor suppressor role and loss in colon cancer patients associated with worse prognosis, suggests that targeting PCs in the control of the malignant phenotype of CSCs is a new potential therapeutic strategy in colon cancer.     

Immunoexpression Analysis and Prognostic Value of BLCAP in Breast Cancer

Bladder Cancer Associated Protein (BLCAP, formerly Bc10), was identified by our laboratory as being down-regulated in bladder cancer with progression. BLCAP is ubiquitously expressed in different tissues, and several studies have found differential expression of BLCAP in various cancer types, such as cervical and renal cancer, as well as human tongue carcinoma and osteosarcoma. Here we report the first study of the expression patterns of BLCAP in breast tissue. We analyzed by immunohistochemistry tissue sections of normal and malignant specimens collected from 123 clinical high-risk breast cancer patients within the Danish Center for Translational Breast Cancer Research (DCTB) prospective study dataset. The staining pattern, the distribution of the immunostaining, and its intensity were studied in detail. We observed weak immunoreactivity for BLCAP in mammary epithelial cells, almost exclusively localizing to the cytoplasm and found that levels of expression of BLCAP were generally higher in malignant cells as compared to normal cells. Quantitative IHC analysis of BLCAP expression in breast tissues confirmed this differential BLCAP expression in tumor cells, and we could establish, in a 62-patient sample matched cohort, that immunostaining intensity for BLCAP was increased in tumors relative to normal tissue, in more than 45% of the cases examined, indicating that BLCAP may be of value as a marker for breast cancer. We also analyzed BLCAP expression and prognostic value using a set of tissue microarrays comprising an independent cohort of 2,197 breast cancer patients for which we had follow-up clinical information.     

Clinico-genetical studies of colonic cancer. II. Genetic analysis of predisposition to colonic cancer

The structure of subjection to different clinical forms of colon cancer and to the morbidity as a whole approximates better the quasi-continued phenotypical model within which the contribution of genetic factors reaches 68-84%, that of incidental medium factors being 16-32%. Genetic study of heterogeneity of colon cancer clinical forms revealed that their pathogenetic community was quite high. However, the origin of colon cancer depends strongly on genetic factors (83.7 +/- 7.3%), in comparison with rectal cancer (67.9 +/- 7.1%). The analysis of colon cancer interrelation with other malignant neoplasms (including specific ones for women--breast and uterus cancer) revealed that the development of another malignant neoplasms was the result of the influence of partially common genes (20-50%) which predetermined the development of colon cancer and other malignant neoplasms. According to the data obtained in this study, the tables of repeated risk have been worked out which may be used for medico-genetic consultation.     

Chloroform extract from Moricandia arvensis inhibits growth of B16-F0 melanoma cells and promotes differentiation in vitro

Objectives: Poor therapeutic results have been reported for treatment of malignant melanoma; therefore in this study we have investigated inhibitory capacity of ethyl acetate, chloroform (Chl) and methanol extracts from Moricandia arvensis on mouse melanoma (B16‐F0) and human keratinocyte (HaCaT) cell proliferation. Influence of Chl extract on percentage distribution in cell cycle phases and melanogenesis was also studied. Material and methods: Cell viability was determined at various periods using the MTT assay, and flow cytometry was used to analyse effects of Chl extract on progression through the cell cycle and apoptosis. In addition, amounts of melanin and tyrosinase were measured spectrophotometrically at 475 nm. Results: Chl extract exhibited significant anti‐proliferative activity after incubation with the two types of tumour skin cells. Morphological changes in B16‐F0 cells, accompanied by increase of tyrosinase activity, and of melanin synthesis were observed, which are markers of differentiation of malignant melanoma cells. Furthermore, cell cycle analysis revealed that B16‐F0 cells treated with Chl extract were arrested predominantly in G₁ phase. Conclusion: Chl extract had the ability to reverse malignant melanoma cells from proliferative to differentiated state, thus providing a new perspective in developing novel strategies for prevention and treatment of malignant melanoma, possibly through consumption of the extract in an appropriate cancer prevention diet. Moreover, there is scope for the extract being introduced into cosmetic products as a natural tanning agent.     

Cancer as an overhealing wound: an old hypothesis revisited

What is the relationship between the wound-healing process and the development of cancer? Malignant tumours often develop at sites of chronic injury, and tissue injury has an important role in the pathogenesis of malignant disease, with chronic inflammation being the most important risk factor. The development and functional characterization of genetically modified mice that lack or overexpress genes that are involved in repair, combined with gene-expression analysis in wounds and tumours, have highlighted remarkable similarities between wound repair and cancer. However, a few crucial differences were also observed, which could account for the altered metabolism, impaired differentiation capacity and invasive growth of malignant tumours.     

Projected estimates of cancer in Canada in 2022

Background:Regular cancer surveillance is crucial for understanding where progress is being made and where more must be done. We sought to provide an overview of the expected burden of cancer in Canada in 2022.Methods:We obtained data on new cancer incidence from the National Cancer Incidence Reporting System (1984–1991) and Canadian Cancer Registry (1992–2018). Mortality data (1984–2019) were obtained from the Canadian Vital Statistics — Death Database. We projected cancer incidence and mortality counts and rates to 2022 for 22 cancer types by sex and province or territory. Rates were age standardized to the 2011 Canadian standard population.Results:An estimated 233 900 new cancer cases and 85 100 cancer deaths are expected in Canada in 2022. We expect the most commonly diagnosed cancers to be lung overall (30 000), breast in females (28 600) and prostate in males (24 600). We also expect lung cancer to be the leading cause of cancer death, accounting for 24.3% of all cancer deaths, followed by colorectal (11.0%), pancreatic (6.7%) and breast cancers (6.5%). Incidence and mortality rates are generally expected to be higher in the eastern provinces of Canada than the western provinces.Interpretation:Although overall cancer rates are declining, the number of cases and deaths continues to climb, owing to population growth and the aging population. The projected high burden of lung cancer indicates a need for increased tobacco control and improvements in early detection and treatment. Success in breast and colorectal cancer screening and treatment likely account for the continued decline in their burden. The limited progress in early detection and new treatments for pancreatic cancer explains why it is expected to be the third leading cause of cancer death in Canada.

The impact of cancer on the Canadian population and health care systems is substantial. Cancer is the leading cause of death in Canada^1,2 and previous estimates have shown that 43% of all people in Canada are expected to receive a cancer diagnosis in their lifetime.³ With an aging and growing population, the number of new cancer cases and deaths in Canada is also increasing.⁴ In addition to its impact on health, cancer is costly. The economic burden of cancer care in Canada rose from $2.9 billion in 2005 to $7.5 billion in 2012, annually.⁵Given the considerable health and economic impact of cancer in Canada, comprehensive and reliable surveillance information is necessary for identifying where progress has been made and where more attention and resources are needed. To meet these needs, the Canadian Cancer Statistics Advisory Committee, in collaboration with the Canadian Cancer Society, Statistics Canada and the Public Health Agency of Canada, produces the latest surveillance statistics on cancer in Canada.Cancer data often lag the current date by several years, owing to the time associated with collecting, verifying and analyzing the data. Short-term cancer incidence and mortality rates can be projected by extrapolating past trends to estimate future trends, using statistical models. These short-term projections provide a more up-to-date estimate of the cancer landscape in Canada. Incidence and mortality counts, along with age-standardized rates, provide a picture of the impact of cancer in Canada, which is essential for resource planning, research and informing cancer-control programs.Canadian Cancer Statistics 2021³ provided detailed estimates of cancer incidence, mortality and survival in Canada by age, sex, geographic region and over time for 22 cancer types.³ Here, we provide updated estimates of the counts and age-standardized rates of new cancer cases (incidence) and cancer deaths (mortality) expected in 2022 by sex and province and territory, for all ages combined.     

Application of nanoparticles in cancer therapy with an emphasis on cell cycle

Owing to their unique characteristics, nanoparticles (NPs) could be incorporated into valuable therapeutic modalities for different diseases; however, there are many concerns about risk factors in human applications. NPs carry therapeutic chemicals that could improve the outcome of cancer therapies. Nowadays, NPs are being recognized as important and strategic agents in treatment of several disorders due to their unique properties in targeting malignant cells in tumor sites. Numerous investigations have shown that the majority of chemotherapeutic agents can be modified through entrapment in submicron colloidal systems. Still, there are problems and limitations in application of NPs in cancer therapy. The aim of the present study is to focus on potential NPs usage in cancer treatment with an emphasis on the cell cycle of malignant cells.     

TNIP1, a retinoic acid receptor corepressor and A20-binding inhibitor of NF-κB, distributes to both nuclear and cytoplasmic locations

An increasingly wide range of functions, from repression of NF-κB signaling to protection from apoptosis, is being recognized for tumor necrosis factor α-induced protein 3-interacting protein 1 (TNIP1). The authors recently demonstrated TNIP1 interaction with and repression of liganded retinoic acid receptors, distinguishing it from the more typical NCoR and SMRT corepressors, which function only in the absence of ligand. To improve their understanding of TNIP1's roles in physiologic and pathologic events, the authors examined its distribution in normal and malignant human tissues and cultured cells. They found cytoplasmic and nuclear TNIP1 in normal skin keratinocytes as it colocalized with retinoic acid receptor α, one of the nuclear receptors it corepresses. Nuclear and cytoplasmic TNIP1 was also found in the malignant keratinocytes of squamous cell carcinomas. Compared to adjacent normal tissues of other organs, TNIP1 staining and distribution varied with increased levels in esophageal cancer and marked decreases in prostate cancer. The varying levels and distribution of TNIP1 in normal and disease state tissues could be expected to affect processes in which TNIP1 is involved, such as NF-κB and nuclear receptor signaling, possibly contributing to the disease course or response to therapies targeting these key players of cell growth and differentiation.     

The genetics of breast cancer. A genetic dispersion analysis and the genetic heterogeneity of breast cancer

The multifactorial nature of breast cancer was established based on population and family study, the contribution of genetic factors being 52% (premenopausal--62 and postmenopausal--39%). Genetic heterogeneity of different coefficients of inheritance of breast cancer with the portion of common genes was shown to be 53%. The analysis of breast cancer interaction with other malignant neoplasms revealed that the development of other malignant neoplasms was the result of the influence of partially common genes. On the basis of data obtained in this study, the tables of repeated risk for the relatives have been worked out which may be used for medico-genetic consultations.     

Receptor-targeted cancer therapy

Insight into the molecular mechanisms of malignant transformation is changing the way cancer is being treated. Conventional treatment strategies target the DNA of all dividing cells, resulting in a significantly increased risk of collateral toxicity. In addition, the accumulation of multiple mutations leads to drug resistance in many cancer cells. Targeted strategies have now been developed that specifically disrupt oncogenically active cell surface receptors and endogenous signaling molecules. These agents have a much greater selectivity for tumor tissue and decreased risk of side effects. Increased signaling through ErbB receptors via gene amplification, overexpression, and mutation has been implicated in many human cancers and associated with poor prognosis. Interruption of this process has been shown to cause antitumor effects. Downregulation of the ErbB receptors, HER-2/neu, and later EGFR, with monoclonal antibodies was the first demonstration of targeted therapy. Subsequently, the ErbB tyrosine kinase domain has been successfully targeted with small molecule inhibitors. The development of novel ErbB-directed entities is ongoing, with particular promise being shown by strategies targeting receptor interaction in oligomeric complexes.     

Surface Temperature Distribution of a Breast With and Without Tumour

Breast cancer is a common and dreadful disease in women. Regular screening helps in its early detection. At present the most common methods of screening are by self examination and mammography. The surface temperature distribution of the breast can also provide some information on the presence of tumour. This distribution has a relation to the size and location of tumour and can be seen using thermography, where the infrared radiation emitted from the surface of the breast is recorded and a thermal pattern obtained. Thermography is a non-invasive and an inexpensive tool which could be used for early detection. In order to simulate the surface temperature distribution, a two-dimensional model of female breast with and without a carcinoma is considered. The breast is modelled with varying layer thickness close to the actual shape and numerically solved using finite element analysis. Temperature profiles are obtained for a normal breast and for a malignant one by varying the tumour size, location and the blood flow rates. The results show that the surface temperature for a malignant breast is higher than that of a normal one. In addition the size and location of the tumour do have an effect on the surface temperature distribution. It can also be seen that tumour of different sizes placed at the same location would yield the same maximum temperature depending on the blood perfusion rate.