Tissue Mechanics and Hedgehog Signaling Crosstalk as a Key Epithelial-Stromal Interplay in Cancer Development.

Epithelial-stromal interplay through chemomechanical cues from cells and matrix propels cancer progression. Elevated tissue stiffness in potentially malignant tissues suggests a link between matrix stiffness and enhanced tumor growth. In this study, employing chronic oral/esophageal injury and cancer models, it is demonstrated that epithelial-stromal interplay through matrix stiffness and Hedgehog (Hh) signaling is key in compounding cancer development. Epithelial cells actively interact with fibroblasts, exchanging mechanoresponsive signals during the precancerous stage. Specifically, epithelial cells release Sonic Hh, activating fibroblasts to produce matrix proteins and remodeling enzymes, resulting in tissue stiffening. Subsequently, basal epithelial cells adjacent to the stiffened tissue become proliferative and undergo epithelial-to-mesenchymal transition, acquiring migratory and invasive properties, thereby promoting invasive tumor growth. Notably, transcriptomic programs of oncogenic GLI2, mechano-activated by actin cytoskeletal tension, govern this process, elucidating the crucial role of non-canonical GLI2 activation in orchestrating the proliferation and mesenchymal transition of epithelial cells. Furthermore, pharmacological intervention targeting tissue stiffening proves highly effective in slowing cancer progression. These findings underscore the impact of epithelial-stromal interplay through chemo-mechanical (Hh-stiffness) signaling in cancer development, and suggest that targeting tissue stiffness holds promise as a strategy to disrupt chemo-mechanical feedback, enabling effective cancer treatment.

Targeting Nuclear Mechanics Mitigates the Fibroblast Invasiveness in Pathological Dermal Scars Induced by Matrix Stiffening.

Pathological dermal scars such as keloids present significant clinical challenges lacking effective treatment options. Given the distinctive feature of highly stiffened scar tissues, deciphering how matrix mechanics regulate pathological progression can inform new therapeutic strategies. Here, it is shown that pathological dermal scar keloid fibroblasts display unique metamorphoses to stiffened matrix. Compared to normal fibroblasts, keloid fibroblasts show high sensitivity to stiffness rather than biochemical stimulation, activating cytoskeletal-to-nuclear mechanosensing molecules. Notably, keloid fibroblasts on stiff matrices exhibit nuclear softening, concomitant with reduced lamin A/C expression, and disrupted anchoring of lamina-associated chromatin. This nuclear softening, combined with weak adhesion and high contractility, facilitates the invasive migration of keloid fibroblasts through confining matrices. Inhibiting lamin A/C-driven nuclear softening, via lamin A/C overexpression or actin disruption, mitigates such invasiveness of keloid fibroblasts. These findings highlight the significance of the nuclear mechanics of keloid fibroblasts in scar pathogenesis and propose lamin A/C as a potential therapeutic target for managing pathological scars.

Advanced materials technologies to unravel mechanobiological phenomena.

Advancements in materials-driven mechanobiology have yielded significant progress. Mechanobiology explores how cellular and tissue mechanics impact development, physiology, and disease, where extracellular matrix (ECM) dynamically interacts with cells. Biomaterial-based platforms emulate synthetic ECMs, offering precise control over cellular behaviors by adjusting mechanical properties. Recent technological advances enable in vitro models replicating active mechanical stimuli in vivo. These models manipulate cellular mechanics even at a subcellular level. In this review we discuss recent material-based mechanomodulatory studies in mechanobiology. We highlight the endeavors to mimic the dynamic properties of native ECM during pathophysiological processes like cellular homeostasis, lineage specification, development, aging, and disease progression. These insights may inform the design of accurate in vitro mechanomodulatory platforms that replicate ECM mechanics.

Mussel-inspired biomaterials: From chemistry to clinic.

After several billions of years, nature still makes decisions on its own to identify, develop, and direct the most effective material for phenomena/challenges faced. Likewise, and inspired by the nature, we learned how to take steps in developing new technologies and materials innovations. Wet and strong adhesion by Mytilidae mussels (among which Mytilus edulis-blue mussel and Mytilus californianus-California mussel are the most well-known species) has been an inspiration in developing advanced adhesives for the moist condition. The wet adhesion phenomenon is significant in designing tissue adhesives and surgical sealants. However, a deep understanding of engaged chemical moieties, microenvironmental conditions of secreted proteins, and other contributing mechanisms for outstanding wet adhesion mussels are essential for the optimal design of wet glues. In this review, all aspects of wet adhesion of Mytilidae mussels, as well as different strategies needed for designing and fabricating wet adhesives are discussed from a chemistry point of view. Developed muscle-inspired chemistry is a versatile technique when designing not only wet adhesive, but also, in several more applications, especially in the bioengineering area. The applications of muscle-inspired biomaterials in various medical applications are summarized for future developments in the field.

Cell Membrane-Cloaked Nanotherapeutics for Targeted Drug Delivery.

Cell membrane cloaking technique is bioinspired nanotechnology that takes advantage of naturally derived design cues for surface modification of nanoparticles. Unlike modification with synthetic materials, cell membranes can replicate complex physicochemical properties and biomimetic functions of the parent cell source. This technique indeed has the potential to greatly augment existing nanotherapeutic platforms. Here, we provide a comprehensive overview of engineered cell membrane-based nanotherapeutics for targeted drug delivery and biomedical applications and discuss the challenges and opportunities of cell membrane cloaking techniques for clinical translation.

Hydrogel membranes: A review.

Hydrogel membranes (HMs) are defined and applied as hydrated porous media constructed of hydrophilic polymers for a broad range of applications. Fascinating physiochemical properties, unique porous architecture, water-swollen features, biocompatibility, and special water content dependent transport phenomena in semi-permeable HMs make them appealing constructs for various applications from wastewater treatment to biomedical fields. Water absorption, mechanical properties, and viscoelastic features of three-dimensional (3D) HM networks evoke the extracellular matrix (ECM). On the other hand, the porous structure with controlled/uniform pore-size distribution, permeability/selectivity features, and structural/chemical tunability of HMs recall membrane separation processes such as desalination, wastewater treatment, and gas separation. Furthermore, supreme physiochemical stability and high ion conductivity make them promising to be utilised in the structure of accumulators such as batteries and supercapacitors. In this review, after summarising the general concepts and production processes for HMs, a comprehensive overview of their applications in medicine, environmental engineering, sensing usage, and energy storage/conservation is well-featured. The present review concludes with existing restrictions, possible potentials, and future directions of HMs.

Metal-Organic Framework (MOF)/Epoxy Coatings: A Review.

Epoxy coatings are developing fast in order to meet the requirements of advanced materials and systems. Progress in nanomaterial science and technology has opened a new era of engineering for tailoring the bulk and surface properties of organic coatings, e.g., adhesion to the substrate, anti-corrosion, mechanical, flame-retardant, and self-healing characteristics. Metal-organic frameworks (MOFs), a subclass of coordinative polymers with porous microstructures, have been widely synthesized in recent years and applied in gas and energy storage, separation, sensing, environmental science and technology, and medicine. Nevertheless, less attention has been paid to their performance in coatings. Well-known as micro- and nanoporous materials, with a tailorable structure consisting of metal ions and organic linkers, MOFs have a huge loading capacity, which is essential for the delivery of corrosion inhibitors. This review paper attempts to highlight the importance of epoxy/MOF composites for coating applications. A particular emphasis was explicitly placed on the anti-corrosion, flame-retardant, mechanical, and dielectric properties of epoxy/MOF coatings.

Agarose-based biomaterials for advanced drug delivery.

Agarose is a prominent marine polysaccharide representing reversible thermogelling behavior, outstanding mechanical properties, high bioactivity, and switchable chemical reactivity for functionalization. As a result, agarose has received particular attention in the fabrication of advanced delivery systems as sophisticated carriers for therapeutic agents. The ever-growing use of agarose-based biomaterials for drug delivery systems resulted in rapid growth in the number of related publications, however still, a long way should be paved to achieve FDA approval for most of the proposed products. This review aims at a classification of agarose-based biomaterials and their derivatives applicable for controlled/targeted drug delivery purposes. Moreover, it attempts to deal with opportunities and challenges associated with the future developments ahead of agarose-based biomaterials in the realm of advanced drug delivery. Undoubtedly, this class of biomaterials needs further advancement, and a lot of critical questions have yet to be answered.

Agarose-Based Biomaterials: Opportunities and Challenges in Cartilage Tissue Engineering.

The lack of adequate blood/lymphatic vessels as well as low-potential articular cartilage regeneration underlines the necessity to search for alternative biomaterials. Owing to their unique features, such as reversible thermogelling behavior and tissue-like mechanical behavior, agarose-based biomaterials have played a key role in cartilage tissue repair. Accordingly, the need for fabricating novel highly efficient injectable agarose-based biomaterials as hydrogels for restoration of injured cartilage tissue has been recognized. In this review, the resources and conspicuous properties of the agarose-based biomaterials were reviewed. First, different types of signals together with their functionalities in the maintenance of cartilage homeostasis were explained. Then, various cellular signaling pathways and their significant role in cartilage tissue engineering were overviewed. Next, the molecular structure and its gelling behavior have been discussed. Eventually, the latest advancements, the lingering challenges, and future ahead of agarose derivatives from the cartilage regeneration perspective have been discussed.

From microporous to mesoporous mineral frameworks: An alliance between zeolite and chitosan.

Microporous and mesoporous minerals are key elements of advanced technological cycles nowadays. Nature-driven microporous materials are known for biocompatibility and renewability. Zeolite is known as an eminent microporous hydrated aluminosilicate mineral containing alkali metals. It is commercially available as adsorbent and catalyst. However, the large quantity of water uptake occupies active sites of zeolite making it less efficient. The widely-used chitosan polysaccharide has also been used in miscellaneous applications, particularly in medicine. However, inferior mechanical properties hampered its usage. Chitosan-modified zeolite composites exhibit superior properties compared to parent materials for innumerable requests. The alliance between a microporous and a biocompatible material with the accompaniment of negative and positive charges, micro/nanopores and proper mechanical properties proposes promising platforms for different uses. In this review, chitosan-modified zeolite composites and their applications have been overviewed.

Synthesis of pearl necklace-like ZIF-8@chitosan/PVA nanofiber with synergistic effect for recycling aqueous dye removal.

Recently, fabrication of MOF-based bionanocomposites for wastewater treatment applications is enjoying wide currency. Herein, zeolitic imidazolate framework-8 (ZIF-8) crystal was coated on chitosan/polyvinyl alcohol electrospun nanofiber (CS/PVA-ENF) to synthesize ZIF-8@CS/PVA-ENF. They were characterized, and their dye adsorption performances were studied in detail. The ZIF-8 was coated on CS/PVA-ENF for the first cycle (ZIF-8@CS/PVA-ENF(1)), second cycle (ZIF-8@CS/PVA-ENF(2)), and third cycle (ZIF-8@CS/PVA-ENF(3)). The impact of operational parameters including pH, the dose of adsorbent, and initial Malachite green (MG) concentration was evaluated and modeled by mostly-known statistical tools such as an artificial neural network (ANN) and response surface methodology (RSM). The mathematical calculation indicated that the obtained data were in high agreement with the Langmuir isotherm, and the kinetics data were well fitted to the pseudo-second-order model. The ZIF-8@CS/PVA-ENF(2) showed a higher Langmuir adsorption capacity (1000 mg/g) in comparison to other composites. Moreover, a cycling experiment shoed ZIF-8@CS/PVA-ENF(2) has high chemical stability.

In situ deposition of Ag/AgCl on the surface of magnetic metal-organic framework nanocomposite and its application for the visible-light photocatalytic degradation of Rhodamine dye.

Herein, NH2-MIL-125(Ti) (NMT) as one of the known stable metal-organic frameworks (MOFs) in aqueous solution was successfully magnetized with CoFe2O4 nanoparticles through the hydrothermal method. The Ag/AgCl as a plasmonic photocatalyst was assembled on the CoFe2O4/NMT (CFNMT) at room temperature by in situ deposition, and photo-reduction methods to improve the photocatalytic activity of CFNMT under LED visible light. The prepared materials were fully characterized by SEM/EDX, TEM, FTIR, XRD, UV-DRS, and VSM analysis. Rhodamin B (RhB) was selected as the pollutant model. The results showed that the Ag/AgCl@CFNMT had super-fast degradation ability of RhB molecule due to the synergetic effect between Ag/AgCl and CFNMT in comparison with NMT and CFNMT. The introduced Ag/AgCl on the surface of CFNMT increased absorption of photons in the visible region and enhanced the transfer and separation of the produced charge on the contact area between Ag/AgCl and CFNMT. Also, after seven times recycling, besides the simple magnetic separation of Ag/AgCl@CFNMT from liquid media, the composite still showed high photodegradation ability (89%).

Novel magnetic amine functionalized carbon nanotube/metal-organic framework nanocomposites: From green ultrasound-assisted synthesis to detailed selective pollutant removal modelling from binary systems.

Herein, magnetic amine functionalized carbon nanotube (NH2-CNT/Fe2O3)-zeolitic imidazolate framework-8 (ZIF-8) nanocomposites (NH2-CNT/Fe2O3/ZIF-8: NCFZ) with different amounts of NH2-CNT/Fe2O3 (5, 10, and 15 wt% denoted as NCFZ-5, NCFZ-10, and NCFZ-15) were synthesized. The synthesized nanomaterials including ZIF-8, Fe2O3, CNT/Fe2O3, NH2-CNT/Fe2O3, CNT/Fe2O3/ZIF-8, NCFZ-5, NCFZ-10, and NCFZ-15 were characterized using BET, TEM, XRD, SEM, FTIR, VSM and zeta potential. The synthesized nanomaterials were applied for selective removing cationic dyes (MG: Malachite Green and RhB: Rhodamine B) from a binary system. Response surface methodology (RSM) and artificial neural networks (ANN) were used for optimizing dye removal. The BET data showed that the surface area of nanocomposite (NH2-CNT/Fe2O3/ZIF-8: 1659 m2/g) was higher than that of pure ZIF-8 (1485 m2/g). Contaminant removal obeyed the Freundlich isotherm and pseudo-second order kinetic models. The optimum adsorption condition predicted by RSM was pH = 6, dye concentration = 25 mg/L, Dosage = 0.004 g and at time = 145 min. The outputs of ANN model well overlapped with the experimental data. The binary system dye removal data indicated the synthesized nanocomposite with recycling and regeneration ability could be used for treating wastewater.

Activated carbon/metal-organic framework nanocomposite: Preparation and photocatalytic dye degradation mathematical modeling from wastewater by least squares support vector machine.

Herein, Kiwi peel activated carbon (AC), Materials Institute Lavoisier (MIL-88B (Fe), and AC/MIL-88B (Fe) composite were synthesized and used as catalysts to degrade Reactive Red 198. The material properties were analyzed by the FTIR, BET-BJH, XRD, FESEM, EDX, TGA, and UV-Vis/DRS. The BET surface area of AC, MIL-88B (Fe) and AC/MIL-88B (Fe) was 1113.3, 150.7, and 199.4 m2/g, respectively. The band gap values (Eg) estimated by Tauc plot method, were obtained 5.06, 4.19 and 3.79 eV for AC, MIL-88B (Fe) and AC/MIL-88B (Fe), respectively. The results indicated that the AC/MIL-88B (Fe) composite had higher photocatalytic activity (99%) than that of pure AC (79%) and MIL-88B (Fe) catalysts (87%). The decolorization kinetic was matched well with the second-order model. Moreover, the data were modeled using least squares support vector machine which optimized with Cuckoo optimization algorithm. The optimal parameters were found 0.837 and 3.49e+02 based on σ2 and γ values, respectively. The mean square error (MSE) and correlation coefficient (R2) values were obtained 3.97 and 0.948. Therefore, the attained data, materials characterization and prediction of modeling validate the composite form of MIL-88B(Fe) with new AC, had better photocatalytic activity in comparison with the individual form.

The Incidence of Deep Vein Thrombosis in Breast Cancer Patients Receiving Outpatient Cancer Therapy in Iran.

BACKGROUND: Venous thromboembolism (VTE) is one of the main causes of mortality in patients with cancer. This study was conducted to assess the incidence of deep vein thrombosis (DVT) in breast cancer patients receiving outpatient cancer therapy. MATERIALS AND METHODS: This multi-center prospective cohort study was conducted on patients with breast cancer, initiating an outpatient chemotherapy regimen in five medical centers in Iran. Eligible patients were enrolled in the study consecutively between January 2013 and January 2015. The primary outcome was lower extremity DVT based on duplex/doppler ultrasonography two months after the first course of chemotherapy (visit 2) and after the end of the course (visit 3). All patients were followed-up from the onset of chemotherapy until the first occurrence of lower extremity DVT, death, or the end of the course. RESULTS: A total of 427 eligible breast cancer patients were recruited in the study, 403 of whom attended at least one follow-up visit. The mean (SD) duration of follow-up was 4 (1.3) months. During the follow-up, only one patient showed DVT on duplex/doppler ultrasonography in visit 2. Therefore, the two-month and overall cumulative incidence risk of DVT was 0.25% (95% CI: 0.00-0.74%). However, the mean D-dimer level showed no significant change (P>0.05). CONCLUSION: Our findings showed the low risk of DVT in breast cancer patients receiving outpatient cancer therapy.

Effect of Persian Medicine Remedy on Chemotherapy Induced Nausea and Vomiting in Breast Cancer: A Double Blind, Randomized, Crossover Clinical Trial.

BACKGROUND: Chemotherapy induced nausea and vomiting (CINV) is a side effect, and has negative effect on quality of life and continuation of chemotherapy. Despite new regimen and drugs, the problems still remain and standard guidelines, effective treatment and supportive care for refractory CINV are still not yet established. Persian medicine, the old Iranian medical school, offer Persumac (prepared from Rhus Coriaria and Bunium Persicum Boiss). OBJECTIVE: The specific objectives were to assess the effect of Persumac on the number and severity of nausea and vomiting in refractory CINV in acute and delayed phase. METHODS: This randomized, double blind, crossover clinical trial study was carried out on 93 patients with breast cancer and refractory CINV, who received outpatient high emetogenic chemotherapy in Imam Reza hospital, Mashhad, Iran from October 2015 to May 2016. The study has three stages: in stage I patients received a questionaire and completed it after chemotherapy. In stage II they were randomly divided into intervention group with Persumac and control group with placebo (lactose were used). In stage III, wash out and crossover was conducted. Both groups in all stages received standard antiemetic therapy for CINV. The following were set as the inclusion criteria of the study: female, Age ≥18 years, clinical diagnosis of breast cancer, history of refractory CINV, normal blood tests and at least three courses of chemotherapy remaining. Exclusion criteria of this study were: Total or upper abdominal radiation therapy along with chemotherapy, drugs/therapy for nausea and vomiting not prescribed in this study, hypersensitivity to Sumac or Bunium Persicum, use of sumac and Bunium Persicum in seven days prior to the intervention, clinical diagnosis of digestion disorders, non-chemotherapy induced nausea and vomiting, milk allergy, loss of two consecutive or three intermittent doses of Persumac or placebo. Outcomes were gathered by Persian questionnaire. Number and severity of nausea and vomiting was measured with a self-reporting tool; visual analog scale. RESULTS: Demographic data and other characters in both groups have no significant diffrence. Eighty of 93 eligible patients in stage I completed the study and in stage II, eleven declined participation for stage III (crossover). P value of carry over, period and treatment effects demonstrated that they had not affected the results before and after crossover. The mean severity of nausea in acute phase was in stage I: 4.83 ± 1.40, stage II: 4.54 ± 2.0 and stage III: 4.15 ± 0.92 in sequence AB (first Persumac and then placebo in crossover), and in sequence BA (first placebo and then Persumac in crossover) was respectively 4.83 ± 1.40, 4.54 ± 2.0, 4.15 ± 0.92 with p value of carry over effect: 0.03 and period effect: 0.22. Except for severity of nausea in acute phase, the mean number and severity of nausea and vomiting scores significantly decreased in acute and delayed phase of CINV. CONCLUSION: Persumac may control the refractory CINV. The implicable and clinical importance of this research is that another option exists for refractory CINV. Higher doses, different cancers, patients with more various features, and more complete methodology and tools can provide appropriate designs for new research on this topic. TRIAL REGISTRATION: This trial was registered at the Clinical Trials.gov ID: NCT02787707. FUNDING: This study is part of a Ph.D. thesis and under grant; No: 930735 of Research Chancellery of MUMS.

Nausea and vomiting in Iranian Traditional Medicine based on Avicenna's viewpoint.

BACKGROUND: Nausea and vomiting decrease one's quality of life significantly, and, despite various treatments, they are still uncontrollable, especially in acute illness. Perhaps it would be useful to search for new concepts and therapies for dealing with these issues at other medical schools. The aim of this research was to elucidate the causes of nausea and vomiting in Iranian Traditional Medicine (ITM) based on Avicenna's viewpoint in The Book of "Canon of medicine". METHODS: We reviewed the Canon of Medicine and other reference textbooks of ITM to get the experts' viewpoints, such as Kamel-al-Sanaeh, Al-Havi, and Zakhireh-kharazmshahi, and we searched PubMed, Scopus, Embase, ISI and Science Iranian Database (SID) in November and December 2014 using keywords. RESULTS: Basic terms associated with nausea and vomiting in ITM are Gha'y (vomiting), Tahavo'a (retching), Gathayan (nausea), and Taghallob-al-nafs (continuous nausea). Different factors can induce these problems with direct or indirect change in the quantity/quality of humors in the body's systems or the stomach. Treatments are based on the correction of humors and modifications of lifestyle. ITM has recommended medicinal herbs for severe nausea and vomiting. For example, they may be effective in treating chemotherapy-induced nausea and vomiting (CINV). CONCLUSION: ITM suggests that almost the nausea and vomiting associated with almost all major diseases originate from abnormalities in either the quantity/quality of humors. The gold standard for managing nausea and vomiting is lifestyle modifications with attention to responsible humors. Some therapeutic protocols in ITM may be applicable today. Perhaps redefining the diseases and updating the expression of these concepts and approaches can lead to the development of complementary and alternative treatments for nausea and vomiting.

Multicentric myxoid liposarcoma; a case report and literature review.

Liposarcoma is a common malignant soft tissue tumor, accounting for 10% to 16% of all sarcomas. Multicentric myxoid liposarcoma is an uncommon condition. Differentiation between several primary tumors and metastasis of a single liposarcoma represents the main difficulty in diagnosis. A 47-years old woman presented with right thigh myxoid liposarcoma and underwent wide margin tumor resection. Other investigations like CXR, abdominal and pelvic CT-scans were negative. After 18 months another myxoid liposarma was found in her ipsi-lateral breast without any evidence of other organs metastasis. Second lesion location, time between two presentation and cytogenetic differences are accepted criteria to site a sarcoma in multicentric category, but in myxoid liposarcoma these can be explained by the special features inherent to this tumor.

Attitude of cancer patients toward diagnosis disclosure and their preference for clinical decision-making: a national survey.

OBJECTIVES: There is still contradictory evidence on disclosure preferences regarding cancer diagnosis. The aim of this study was to evaluate the preference of cancer patients for knowing the truth about their disease, as well as the factors that might have an impact on these preferences. METHOD: This study was conducted in 11 cancer centers in Iran. A questionnaire was used to collect data, and all patients above 15 years of age who were willing to participate were included in the study. The patients were asked if they were aware of the malignant nature of their disease, and if they came to know about their disease at the time of initial diagnosis, or later. The patients were then asked about the way they looked upon their disease. In the final part of the questionnaire, the participants were asked the level of involvement they prefer to have in making treatment decisions. RESULTS: In total, 1226 patients were enrolled in this study, only 565 (46.7%) of whom were aware of their disease at the time of diagnosis, and 878 (72.7%) at the time of interview, while 980 (85.2%) were willing to receive information about their disease. Patients' awareness was significantly associated with age under 50 years, female gender, having breast, skin or head and neck cancer, and having medical care in Shiraz or Hamadan while it was not associated with the stage or accompanying illness. CONCLUSION: While the majority of Iranian cancer patients prefer to be aware of the nature of their disease and have an active role in treatment decision making, they do not receive this information.

Comparison of hormone receptor status in primary and recurrent breast cancer.

BACKGROUND: Systematic treatments such as hormone and chemotherapy are selected according to tumor characteristic after major therapeutic approaches such as surgery. This study attempted to analyze and compare the status of Estrogen Receptor (ER) and Progesterone Receptor (PR) in primary and recurrent sites of breast cancer in patients. METHODS: We reviewed all medical records of breast cancer women who were treated between January 1995 and December 2008. One hundred eighty two out of 2241 patients (8.12%) had a metastatic breast cancer. Amongst them 48 patients had tumor and biopsy-driven samples, however 13 samples were destroyed and only 35 samples were investigated in this study, therefore 35 malignant biopsy specimens of breast cancer patients were examined by immunohistochemistry essay for ER and PR. Binominal proportional test and Chi square test were conducted to determine the significant correlation between positive cases of hormone receptors among primary and metastases sites. RESULTS: Hormone Receptor in the primary tumor (HR1) of 9 patients (25.7%) was positive (ER1 and/or PR1) and in the recurrent areas (HR2) of 8 patients (22.9%) was positive (either ER2 or PR2 positive). Kappa coefficients of diagnostic agreement in primary and recurrent cases were 0.077 and 0.125 for estrogen and progesterone, respectively which indicated that the amount of coefficient of agreement is not considerable between primary and recurrent sites. CONCLUSION: The current study indicated that receptor status in recurrent tumors did not pose predictable value based on the analysis of hormone receptors in primary stage, so it is not an appropriate basis to set up therapeutic protocol in the metastatic patients. Therefore, tissue sampling and hormone receptor re-analyzing of metastatic sites should be considered in these cases.