Search results for: cancer pain

Authors: H. Yousefnia, R. Enayati, M. Hosntalab, S. Zolghadri, A. Bahrami-Samani

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Bone metastases occur in many cases at an early stage of the tumour disease, however their symptoms are recognized rather late. The aim of this study was the preparation of 153Sm-(4-{[bis-(phosphonomethyl))carbamoyl]methyl}-7,10-bis(carboxymethyl) 1,4,7,10-tetraazacyclododec-1-yl) acetic acid (BPAMD) for bone pain palliation therapy. 153Sm was produced at Tehran research reactor via 152Sm(n,γ)153Sm reaction. 200 µl of 1mg/ml BPAMD solution was added to the vial containing 1 mCi 153Sm and the mixture was heated up to 90 0C for 1 h. The radiochemical purity of the complex was measured by ITLC method. The final solution with radiochemical purity of more than 95% was injected to BALB mice and bio distribution was determined up to 48 h. SPECT images were acquired after 2 and 24 h post injection. While high bone uptake was confirmed by both the bio distribution studies and SPECT imaging, accumulation in other organs was approximately negligible. The results show that 153Sm-BPAMD can be used as an excellent tracer for bone pain palliation therapy.

Keywords: bone metastases, BPAMD, 153Sm, radiotherapy

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Authors: Hanno Schmidt, Assaf Malik, Anne Bicker, Gesa Poetzsch, Aaron Avivi, Imad Shams, Thomas Hankeln

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The blind subterranean mole rat Spalax shows a remarkable tolerance to hypoxia, cancer-resistance and longevity. Unravelling the genomic basis of these adaptations will be important for biomedical applications. RNA-Seq gene expression data were obtained from normoxic and hypoxic Spalax and rat liver tissue. Hypoxic Spalax broadly downregulates genes from major liver function pathways. This energy-saving response is likely a crucial adaptation to low oxygen levels. In contrast, the hypoxiasensitive rat shows massive upregulation of energy metabolism genes. Candidate genes with plausible connections to the mole rat’s phenotype, such as important key genes related to hypoxia-tolerance, DNA damage repair, tumourigenesis and ageing, are substantially higher expressed in Spalax than in rat. Comparative liver transcriptomics highlights the importance of molecular adaptations at the gene regulatory level in Spalax and pinpoints a variety of starting points for subsequent functional studies.

Keywords: cancer, hypoxia, longevity, transcriptomics

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Authors: Raymond C. Hawkins II, Catherine A. Hawkins

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The System Contextual Integrated Model (SCIM), developed as a trans-theoretical framework for selecting measures for psychotherapy process and outcome, is reformulated for behavioral health applications. The SCIM “healing cycle” is an allostatic hedonic affective-cognitive right-hemisphere–left-hemisphere coordinated process involving positive alliesthesia that mitigates traumatic pain and generates psychological flexibility. The SCIM “trauma cycle” is an allostatic overload alliesthesia opponent process with long-lasting pathology sequelae. The social ecological context moderates the “healing cycle” and the “trauma cycle.” Repeated evocation of the “healing cycle” in a therapeutic relationship can gradually relieve trauma sequelae. The SCIM is applied to pain, obese binge eating, and substance use disorders.

Keywords: allostasis, alliesthesia, opponent process, behavioral health, assessment

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Authors: Mustafa Gulsen, Mitat Koz

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The aim of this study is to investigate the effect of lumbar stabilisation and proprioceptive neuromuscular facilitation (PNF) training on muscle strength and muscle endurance. The participants were 64 between the ages of 15-69 (53.04 ± 14.59), who were graded protrusion and bulging lumbar herniation according to 'Macnab Classification'. The participants were divided into four groups as each group had 16 participants: lumbar stabilitation training, PNF training, physical therapy and control groups. Sociodemographic features were recorded. Then their muscle strength tests (by isokinetic dynamometer (Cybex 770 Norm Lumex Inc, Ronkonkoma, NY, USA) were recorded. Before and after applications; visual analogue scale (VAS), Oswestry Disability İndex were applied by a physical therapist. The participants in lumbar stabilisation group performed 45 minutes, 5 days in a week for 4 weeks strength training with a physical therapist observation. The participants in PNF group performed 5 days in a week for 4 weeks with pelvic patterns of PNF by a physiotherapist. The participants in physical therapy group underwent Hotpack, Tens and Ultrasound therapy 5 days in a week for 4 weeks. The participants in control group didn’t take any training programme. After 4 weeks, the evaluations were repeated. There were significant increases in muscle strength and muscle endurance in lumbar stabilization training group. Also in pain intensity at rest and during activity in this group and in Oswestry disability index of patients, there were significant improvements (p < 0.05). In PNF training group likewise, there were significant improvements in muscle strength, muscle endurance, pain intensity at rest and with activity and in Oswestry disability index (p < 0.05). But improvements in the Lumbar Stabilization group was better than PNF Group. We found significant differences only in pain intensity at rest and with activity and in Oswestry disability index (p < 0.05). in the patients in Physical Therapy group. We think that appropriate physiotherapy and rehabilitation program which will be prepared for patients, to protect the waist circumference of patients with low muscle strength and low muscle endurance will increase muscle strength and muscle endurance. And it is expected that will reduce pain and will provide advances toward correcting functional disability of the patients.

Keywords: disc herniation, endurance, lumbar stabilitation exercises, PNF, strength

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Authors: Akbar Haghzadeh Saraskanroud, Amir Hossein Yahyavi Zanjani, Niloofar Kargar, Hanieh Ahrabi

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Cervical cancer refers to an unusual growth of cells in the cervix. The cervix is the lower part of the uterus, which connects to the vagina. Various risk factors such as human papillomavirus (HPV), having a weakened immune system, smoking or breathing in secondhand smoke, reproductive factors, and obesity play important roles in causing most cervical cancers. When cervical cancer happens, surgery is often the first treatment option to remove it. Other treatments might include chemotherapy and targeted therapy medicines. Radiation therapy with high-energy photon beams also may be used. Sometimes combined treatment, including radiation with low-dose chemotherapy, was applied. Intracavitary brachytherapy is an integral part of radiotherapy for locally advanced gynecologic malignancies such as cervical cancer. In the treatment of cervical cancer, there are different tools for doing brachytherapy. Two combinations of different applicators for this purpose are Tandem and Ovoid and Tandem and Ring. This study evaluated the dose differences between these two methods in the organs at risk of the rectum, sigmoid, and bladder. In this study, the treatment planswere simulated by the Oncentra treatment planning system and Tandem, Ovid, and Rings of different sizes. CT scan images of 23 patients were treated with HDR_BT Elekta Flexitron system were used for this study. Contouring of HR-CTV, rectum and bladder was performed for all patients. Then, the received dose of 0.1 and 0.2cc volumes of organs at risk were obtained and compared for these two methods: T-Ovoid and T-Ring. By doing investigations and dose measurements of points A and B and the volumes specified by ICRU, it seems that when comparing ring and ovoid to tandem and ovoid, the total dose to the rectum was lower by about 11%, and the bladder was 7%. In the case of HR CTV, this comparison showed that this ratio is about 7% better. Figure 1 shows the amount of decrease in rectum dose in the T-Ring method compared to T-Ovoid. Figure 2 indicates the amount of decrease in bladder dose in the T-Ring method compared to T-Ovoid. Finally, figure 3 illustrates the amount of HR-CTV coverage in the T-Ring method compared to the T-Ovoid.

Keywords: cervical cancer, brachytherapy, rectum, tandem and ovoid, tandem and ring.

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Authors: Iulianna Taritsa, Kuldeep Neote, Eric Fossel

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Lysosome-induced immunogenic cell death (LIICD) is a powerful mechanism of targeting cancer cells that kills circulating malignant cells and primes the host’s immune cells against future remission. Current immunotherapies for cancer are limited in preventing recurrence – a gap that can be bridged by training the immune system to recognize cancer neoantigens. Lysosomal leakage can be induced therapeutically to traffic antigens from dying cells to dendritic cells, which can later present those tumorigenic antigens to T cells. Previous research has shown that oxidative agents administered in the tumor microenvironment can initiate LIICD. We generated a fusion protein between an oxidative agent known as xanthine oxidase (XO) and a mini-antibody specific for EGFR/HER2-sensitive breast tumor cells. The anti-EGFR single domain antibody fragment is uniquely sourced from llama, which is functional without the presence of a light chain. These llama micro-antibodies have been shown to be better able to penetrate tissues and have improved physicochemical stability as compared to traditional monoclonal antibodies. We demonstrate that the fusion protein created is stable and can induce early markers of immunogenic cell death in an in vitro human breast cancer cell line (SkBr3). Specifically, we measured overall cell death, as well as surface-expressed calreticulin, extracellular ATP release, and HMGB1 production. These markers are consensus indicators of ICD. Flow cytometry, luminescence assays, and ELISA were used respectively to quantify biomarker levels between treated versus untreated cells. We also included a positive control group of SkBr3 cells dosed with doxorubicin (a known inducer of LIICD) and a negative control dosed with cisplatin (a known inducer of cell death, but not of the immunogenic variety). We looked at each marker at various time points after cancer cells were treated with the XO/antibody fusion protein, doxorubicin, and cisplatin. Upregulated biomarkers after treatment with the fusion protein indicate an immunogenic response. We thus show the potential for this fusion protein to induce an anticancer effect paired with an adaptive immune response against EGFR/HER2+ cells. Our research in human cell lines here provides evidence for the success of the same therapeutic method for patients and serves as the gateway to developing a new treatment approach against breast cancer.

Keywords: apoptosis, breast cancer, immunogenic cell death, lysosome

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Authors: Abdulaziz Alakeel, Abdulrahman Alomair, Mohammed Fouda

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Introduction: Methotrexate (MTX) is an antimetabolite used to treat multiple conditions, including neoplastic diseases, severe psoriasis, and rheumatoid arthritis. Skin cancer is the out-of-control growth of abnormal cells in the epidermis, the outermost skin layer, caused by unrepaired DNA damage that triggers mutations. These mutations lead the skin cells to multiply rapidly and form malignant tumors. The aim of this review is to evaluate the risk of skin cancer associated with the use of methotrexate and to suggest regulatory recommendations if required. Methodology: Signal Detection team at Saudi Food and Drug Authority (SFDA) performed a safety review using National Pharmacovigilance Center (NPC) database as well as the World Health Organization (WHO) VigiBase, alongside with literature screening to retrieve related information for assessing the causality between skin cancer and methotrexate. The search conducted in July 2020. Results: Four published articles support the association seen while searching in literature, a recent randomized control trial published in 2020 revealed a statistically significant increase in skin cancer among MTX users. Another study mentioned methotrexate increases the risk of non-melanoma skin cancer when used in combination with immunosuppressant and biologic agents. In addition, the incidence of melanoma for methotrexate users was 3-fold more than the general population in a cohort study of rheumatoid arthritis patients. The last article estimated the risk of cutaneous malignant melanoma (CMM) in a cohort study shows a statistically significant risk increase for CMM was observed in MTX exposed patients. The WHO database (VigiBase) searched for individual case safety reports (ICSRs) reported for “Skin Cancer” and 'Methotrexate' use, which yielded 121 ICSRs. The initial review revealed that 106 cases are insufficiently documented for proper medical assessment. However, the remaining fifteen cases have extensively evaluated by applying the WHO criteria of causality assessment. As a result, 30 percent of the cases showed that MTX could possibly cause skin cancer; five cases provide unlikely association and five un-assessable cases due to lack of information. The Saudi NPC database searched to retrieve any reported cases for the combined terms methotrexate/skin cancer; however, no local cases reported up to date. The data mining of the observed and the expected reporting rate for drug/adverse drug reaction pair is estimated using information component (IC), a tool developed by the WHO Uppsala Monitoring Centre to measure the reporting ratio. Positive IC reflects higher statistical association, while negative values translated as a less statistical association, considering the null value equal to zero. Results showed that a combination of 'Methotrexate' and 'Skin cancer' observed more than expected when compared to other medications in the WHO database (IC value is 1.2). Conclusion: The weighted cumulative pieces of evidence identified from global cases, data mining, and published literature are sufficient to support a causal association between the risk of skin cancer and methotrexate. Therefore, health care professionals should be aware of this possible risk and may consider monitoring any signs or symptoms of skin cancer in patients treated with methotrexate.

Keywords: methotrexate, skin cancer, signal detection, pharmacovigilance

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Authors: Sanjukta Badhai, Durga Barik, Bairagi C. Mallick

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In the present study, Beta-Sitosterol in Lawsonia methanolic leaf extract embedded in controlled release nanocomposite was prepared and evaluated for in vivo anticancer efficacy in dimethyl hydrazine (DMH) induced colon cancer. In the present study, colon cancer was induced by s.c injection of DMH (20 mg/kg b.wt) for 15 weeks. The animals were divided into five groups as follows control, DMH alone, DMH and Beta Sitosterol nanocomposite (50mg/kg), DMH and Beta Sitosterol nanocomposite (100 mg/kg) and DMH and Standard Silymarin (100mg/kg) and the treatment was carried out for 15 weeks. At the end of the study period, the blood was withdrawn, and serum was separated for haematological, biochemical analysis and tumor markers. Further, the colonic tissue was removed for the estimation of antioxidants and histopathological analysis. The results of the study displays that DMH intoxication elicits altered haematological parameters (RBC,WBC, and Hb), elevated lipid peroxidation and decreased antioxidants level (SOD, CAT, GPX, GST and GSH), elevated lipid profiles (cholesterol and triglycerides), tumor markers (CEA and AFP) and altered colonic tissue histology. Meanwhile, treatment with Beta Sitosterol nanocomposites significantly restored the altered biochemicals parameters in DMH induced colon cancer mediated by its anticancer efficacy. Further, Beta Sitosterol nanocomposite (100 mg/kg) showed marked efficacy.

Keywords: nanocomposites, herbal formulation, henna, beta sitosterol, colon cancer, dimethyl hydrazine, antioxidant, lipid peroxidation

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Authors: Muneeb Nasir, Misbah Masood, Farrukh Rashid, Abubabakar Shahid

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Introduction: Neo-adjuvant chemotherapy is a potent option for triple negative breast cancer (TNBC) as these tumours lack a clearly defined therapeutic target. Several recent studies lend support that pathological complete remission (pCR) is associated with improved disease free survival (DFS) and overall survival (OS) and could be used as surrogate marker for DFS and OS in breast cancer patients. Methods: We have used a four-drug protocol in T3 and T4 TNBC patients either N+ or N- in the neo-adjuvant setting. The 15 patients enrolled in this study had a median age of 45 years. 12 patients went on to complete four planned cycles of B-CAT protocol. The chemotherapy regimen included inj. Bevacizumab 5mg/kg D1, inj. Adriamycin 50mg/m2 D1 and Docetaxel 65mg/m2 on D1. Inj. Cisplatin 60mg/m2 on D2. All patients received GCF support from D4 to D9 of each cycle. Results: Radiological assessment using ultrasound and PET-CT revealed a high percentage of responses. Radiological CR was documented in half of the patients (6/12) after four cycles. Remaining patients went on to receive 2 more cycles before undergoing radical surgery. pCR was documented in 7/12 patients and 3 more had a good partial response. The regimen was toxic and grade ¾ neutropenia was seen in 58% of patients. Four episodes of febrile neutropenia were reported and managed. Non-hematatological toxicities were common with mucositis, diarrhea, asthenia and neuropathy topping the list. Conclusion: B-CAT is a very active combination with very high pCR rates in TNBC. Toxicities though frequent, were manageable on outpatient basis. This protocol warrants further investigation.

Keywords: B-CAT:bevacizumab, cisplatin, adriamycin, taxotere, CR: complete response, pCR: pathological complete response, TNBC: triple negative breast cancer

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Authors: Chukwudalu C. Nwazojie, Wole W. Soboyejo, John Obayemi, Ali Salifu Azeko, Sandra M. Jusu, Chinyerem M. Onyekanne

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The conventional methods for the diagnosis and treatment of breast cancer include bulk systematic mammography, ultrasound, dynamic contrast-enhanced fast 3D gradient-echo (GRE) magnetic resonance imaging (MRI), surgery, chemotherapy, and radiotherapy. However, nanoparticles and drug-loaded polymer microspheres for disease (cancer) targeting and treatment have enormous potential to enhance the approaches that are used today. The goal is to produce an implantable biomedical device for localized breast cancer drug delivery within Africa and the world. The main advantage of localized delivery is that it reduces the amount of drug that is needed to have a therapeutic effect. Polymer blends of poly (D,L-lactide-co-glycolide) (PLGA) and polycaprolactone (PCL), which are biodegradable, is used as a drug excipient. This work focuses on the development of PLGA-PCL (poly (D,L-lactide-co-glycolide) (PLGA) blended with based injectable drug microspheres and are loaded with anticancer drugs (prodigiosin (PG), and paclitaxel (PTX) control) and also the conjugated forms of the drug functionalized with LHRH (luteinizing hormone-releasing hormone) (PG-LHRH, and PTX- LHRH control), using a single-emulsion solvent evaporation technique. The encapsulation was done in the presence of PLGA-PCL (as a polymer matrix) and poly-(vinyl alcohol) (PVA) (as an emulsifier). Comparative study of the various drugs release kinetics and degradation mechanisms of the PLGA-PCL with an encapsulated drug is achieved, and the implication of this study is for the potential application of prodigiosin PLGA-PCL loaded microparticles for controlled delivery of cancer drug and treatment to prevent the regrowth or locoregional recurrence, following surgical resection of triple-negative breast tumor.

Keywords: cancer, polymers, drug kinetics, nanoparticles

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Authors: Aarthi Mariappan, Janani Selvaraj, P. B. Harathi, M. Prashanthi Devi

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Anthropogenic modification of the urban environment has largely increased in the recent years in order to sustain the growing human population. Intense industrial activity, permanent and high traffic on the roads, a developed subterranean infrastructure network, land use patterns are just some specific characteristics. Every day, the urban environment is polluted by more or less toxic emissions, organic or metals wastes discharged from specific activities such as industrial, commercial, municipal. When these eventually deposit into the soil, the physical and chemical properties of the surrounding soil is changed, transforming it into a human exposure indicator. Metals are non-degradable and occur cumulative in soil due to regular deposits are a result of permanent human activity. Due to this, metals are a contaminant factor for soil when persistent over a long period of time and a possible danger for inhabitant’s health on prolonged exposure. Metals accumulated in contaminated soil may be transferred to humans directly, by inhaling the dust raised from top soil, or by ingesting, or by dermal contact and indirectly, through plants and animals grown on contaminated soil and used for food. Some metals, like Cu, Mn, Zn, are beneficial for human’s health and represent a danger only if their concentration is above permissible levels, but other metals, like Pb, As, Cd, Hg, are toxic even at trace level causing gastrointestinal and lung cancers. In urban areas, metals can be emitted from a wide variety of sources like industrial, residential, commercial activities. Our study interrogates the spatial distribution of heavy metals in soil in relation to their permissible levels and their association with the health risk to the urban population in Coimbatore, India. Coimbatore region is a high cancer risk zone and case records of gastro intestinal and respiratory cancer patients were collected from hospitals and geocoded in ArcGIS10.1. The data of patients pertaining to the urban limits were retained and checked for their diseases history based on their diagnosis and treatment. A disease map of cancer was prepared to show the disease distribution. It has been observed that in our study area Cr, Pb, As, Fe and Mg exceeded their permissible levels in the soil. Using spatial overlay analysis a relationship between environmental exposure to these potentially toxic elements in soil and cancer distribution in Coimbatore district was established to show areas of cancer risk. Through this, our study throws light on the impact of prolonged exposure to soil contamination in soil in the urban zones, thereby exploring the possibility to detect cancer risk zones and to create awareness among the exposed groups on cancer risk.

Keywords: soil contamination, cancer risk, spatial analysis, India

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Authors: Priyanka Bhowmik, Subrata Majumdar, Debprasad Chattopadhyay

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Background: Cervical cancer is the third major cause of cancer in women and the second most frequent cause of cancer related deaths causing 300,000 deaths annually worldwide. Evasion of immune response by Human Papilloma Virus (HPV), the key contributing factor behind cancer and pre-cancerous lesions of the uterine cervix, makes immunotherapy a necessity to treat this disease. Objective: A Heat killed fraction of Mycobacterium indicus pranii (MIP), a non-pathogenic Mycobacterium has been shown to exhibit cytotoxic effects on different cancer cells, including human cervical carcinoma cell line HeLa. However, the underlying mechanisms remain unknown. The aim of this study is to decipher the mechanism of MIP induced HeLa cell death. Methods: The cytotoxicity of Mycobacterium indicus pranii against HeLa cells was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis was detected by annexin V and Propidium iodide (PI) staining. The assessment of reactive oxygen species (ROS) generation and cell cycle analysis were measured by flow cytometry. The expression of apoptosis associated genes was analyzed by real time PCR. Result: MIP could inhibit the proliferation of HeLa cell in a time and dose dependent manner but caused minor damage to normal cells. The induction of apoptosis was confirmed by the cell surface presentation of phosphatidyl serine, DNA fragmentation, and mitochondrial damage. MIP caused very early (as early as 30 minutes) transcriptional activation of p53, followed by a higher activation (32 fold) at 24 hours suggesting prime importance of p53 in MIP-induced apoptosis in HeLa cell. The up regulation of p53 dependent pro-apoptotic genes Bax, Bak, PUMA, and Noxa followed a lag phase that was required for the transcriptional p53 program. MIP also caused the transcriptional up regulation of Toll like receptor 2 and 4 after 30 minutes of MIP treatment suggesting recognition of MIP by toll like receptors. Moreover, MIP caused the inhibition of expression of HPV anti apoptotic gene E6, which is known to interfere with p53/PUMA/Bax apoptotic cascade. This inhibition might have played a role in transcriptional up regulation of PUMA and subsequently apoptosis. ROS was generated transiently which was concomitant with the highest transcription activation of p53 suggesting a plausible feedback loop network of p53 and ROS in the apoptosis of HeLa cells. Scavenger of ROS, such as N-acetyl-L-cysteine, decreased apoptosis suggesting ROS is an important effector of MIP induced apoptosis. Conclusion: Taken together, MIP possesses full potential to be a novel therapeutic agent in the clinical treatment of cervical cancer.

Keywords: cancer, mycobacterium, immunity, immunotherapy.

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Authors: Thaer Khaleel Swaid, Maryam Al Ahmad, Ishtiaq Ahmad

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47-year-old female, known to have a liver cyst and hemangiomas, presented to the gastroenterology clinic for chronic moderate postprandial epigastric pain, which is aggravated by food, leaning forward and relieved on lying flat. The pain was associated with nausea, vomiting, heartburn and excessive burping. She opened her bowel daily, having well-formed stools without blood or mucus. The patient denied NSAID intake, smoking or alcohol. On physical examination during the episode of pain abdomen revealed a soft, lax abdomen and mild tenderness in the epigastric region without organomegaly. Bowel sounds were audible. Her routine hematological and biochemical parameters were within normal, including CBC, Celiac serology, Lipase, Metabolic profile and H pylori stool antigen. The patient underwent an Ultrasound of the abdomen which showed multiple liver cysts, hemangioma, normal GB and biliary tree. Based on the clinical picture and to narrow our differential diagnosis, an ultrasound Doppler for the abdomen was ordered, and it showed celiac artery peak systolic velocity in expiration is 270cm/s, suggestive of median arcuate ligament syndrome. She Had computerized tomography abdomen done and showed a Narrowing of the celiac artery at the origin, likely secondary to low insertion of the median arcuate ligament. Furthermore, Gastroscopy and, later on colonoscopy were done, which was unremarkable. A laparoscopic decompression of the celiac trunk was indicated, for which the patient was referred to vascular surgery. This case confirms that Median Arcuate Ligament syndrome is an unusual diagnosis and is always challenging. Usually, patients undergo extensive workups before a final diagnosis is achieved. Our case highlights the challenge of diagnosing MALS since this entity is rare. It is a good choice to perform abdominal ultrasound with Doppler imaging on a patient with symptoms such as postprandial angina.

Keywords: Unveiling the Mystery, MALS, rare entity, Rare vascular phenomenon

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Authors: Sajmina Khatun, Monika Pebam, Aravind Kumar Rengan

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Photothermal therapy, a subset of nanomedicine, takes advantage of light-absorbing agents to generate localized heat, selectively eradicating cancer cells. This innovative approach minimizes damage to healthy tissues and offers a promising avenue for targeted cancer treatment. Unlike conventional therapies, photothermal therapy harnesses the power of light to combat malignancies precisely and effectively, showcasing its potential to revolutionize cancer treatment paradigms. The combined strengths of nanomedicine and photothermal therapy signify a transformative shift toward more effective, targeted, and tolerable cancer treatments in the medical landscape. Utilizing natural products becomes instrumental in formulating diverse bioactive medications owing to their various pharmacological properties attributed to the existence of phenolic structures, triterpenoids, and similar compounds. Hyptis suaveolens, commonly known as pignut, stands as an aromatic herb within the Lamiaceae family and represents a valuable therapeutic plant. Flourishing in swamps and alongside tropical and subtropical roadsides, these noxious weeds impede the development of adjacent plants. Hyptis suaveolens ranks among the most globally distributed alien invasive species. The present investigation revealed that a versatile, biodegradable liposome nanosystem (HIL NPs), incorporating bioactive molecules from Hyptis suaveolens, exhibits effective bioavailability to cancer cells, enabling tumor ablation upon near-infrared (NIR) laser exposure. The components within the nanosystem, specifically the bioactive molecules from Hyptis, function as anticancer agents, aiding in the photothermal ablation of highly metastatic lung cancer cells. Despite being a prolific weed impeding neighboring plant growth, Hyptis suaveolens showcases therapeutic benefits through its bioactive compounds. The obtained HIL NPs, characterized as a photothermally active liposome nanosystem, demonstrate a pronounced fluorescence absorption peak in the NIR range and achieve a high photothermal conversion efficiency under NIR laser irradiation. Transmission electron microscopy (TEM) and particle size analysis reveal that HIL NPs possess a spherical shape with a size of 141 ± 30 nm. Moreover, in vitro assessments of HIL NPs against lung cancer cell lines (A549) indicate effective anticancer activity through a combined cytotoxic effect and hyperthermia. Tumor ablation is facilitated by apoptosis induced by the overexpression of ɣ-H2AX, arresting cancer cell proliferation. Consequently, the multifunctional and biodegradable nanosystem (HIL NPs), incorporating bioactive compounds from Hyptis, provides valuable perspectives for developing an innovative therapeutic strategy originating from a challenging weed. This approach holds promise for potential applications in both bioimaging and the combined use of phyto-photothermal therapy for cancer treatment.

Keywords: bioactive liposome, hyptis suaveolens, photothermal therapy, lung cancer

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Authors: Janani Selvaraj, M. Prashanthi Devi, P. B. Harathi

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Epidemiologic studies conducted over several decades have provided evidence to suggest that long-term exposure to elevated ambient levels of particulate air pollution is associated with increased mortality. Air quality risk management is significant in developing countries and it highlights the need to understand the role of ecologic covariates in the association between air pollution and mortality. Several new methods show promise in exploring the geographical distribution of disease and the identification of high risk areas using epidemiological maps. However, the addition of the temporal attribute would further give us an in depth idea of the disease burden with respect to forecasting measures. In recent years, new methods developed in the reanalysis were useful for exploring the spatial structure of the data and the impact of spatial autocorrelation on estimates of risk associated with exposure to air pollution. Based on this, our present study aims to explore the spatial and temporal distribution of the lung cancer cases in the Coimbatore district of Tamil Nadu in relation to air pollution risk areas. A spatio temporal moving average method was computed using the CrimeStat software and visualized in ArcGIS 10.1 to document the spatio temporal movement of the disease in the study region. The random walk analysis performed showed the progress of the peak cancer incidences in the intersection regions of the Coimbatore North and South taluks that include major commercial and residential regions like Gandhipuram, Peelamedu, Ganapathy, etc. Our study shows evidence that daily exposure to high air pollutant concentration zones may lead to the risk of lung cancer. The observations from the present study will be useful in delineating high risk zones of environmental exposure that contribute to the increase of cancer among daily commuters. Through our study we suggest that spatially resolved exposure models in relevant time frames will produce higher risks zones rather than solely on statistical theory about the impact of measurement error and the empirical findings.

Keywords: air pollution, cancer, spatio-temporal analysis, India

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Authors: Aliaa M. Issa, Mahmoud N. ElRouby, Sahar A. S. Ahmad, Mahmoud M. El-Merzabani

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Sider honey is a type of honey produced by bees feeding on the nectar of Sider tree, Ziziphus spina-christi (L) Desf . Honey is an effective agent for preventing, inhibiting and treating the growth of human and animal cancer cell lines in vitro and in vivo. The aim of the present study was to evaluate the impact of different dilutions from crude Sider honey and different duration times of exposure on the growth of six tumor cell lines (human cervical cancer cell line, HeLa; human hepatocellular carcinoma cell line, HepG-2; human larynx carcinoma cell line, Hep-2; brain tumor cell line, U251) as well as one animal cancerous cell line (Ehrlich ascites carcinoma cells line, EAC) and one normal cell line, Homo sapiens, human, (WISH) CCL-25. Different concentrations and treatment durations with Sider honey were tested on the growth of several cancer cell lines types. Histopathological changes in the tumor masses, animal survival, apoptosis and necrosis of the used cancer cell lines (using flow cytometry) were evaluated. Sider honey was administers either to the tumor mass itself by intratumoral injection or via drinking water. One-way ANOVA test was used for the analysis of (the means + standard error) of the optical density obtained from the Elisa reader and flow cytometry. The study revealed that different concentrations of Sider honey affected the growth patterns of all the studied cancer cell lines as well as their histopathological changes, and it depended on the cell line nature and the concentration of honey used. It is obvious that the relative animal survival percentage (bearing Ehrlich ascites carcinoma, EAC cells) was proportionally increased with the increase in the used honey concentrations. The study of apoptosis and necrosis using the flow cytometry technique emphasized the viability results. In conclusion, Sider honey was effective as antitumor agent, in the used concentrations.

Keywords: antitumor, honey, sider, tumor cell lines

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Authors: Hien Thi Thu Le, Nuno Rafael Candeias, Olli Yli-Harja, Meenakshisundaram Kandhavelu

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Purinergic receptor 1 (P2Y1R) is the potential therapeutic target for inducing prostate cancer (PCa) cell death. Recently, 1-indolinoalkyl 2-phenolic derivative, HIC, was identified as a P2Y1R agonist that increases apoptosis and inhibits cell proliferation of PCa. However, the biological effects of HIC have not been extensively studied at the molecular level. In the present study, we have investigated the anticancer effects of HIC and the molecular mechanisms underlying in PCa cells. Half maximal inhibitory concentration (IC₅₀) of HIC was measured as 15.98 μM and 15.64 μM for DU145 and PC3 cells, respectively. In addition, we found that HIC inhibited cell growth and metastasis of PC3 and DU145 cells colonies, spheroid areas, and migrated cells. RNA seq analysis revealed significant changes of over 3000 genes (p value < 0.05) upon HIC treatment in PC3 and DU145 cells. Genes involved in DNA damage, apoptosis, cell cycle arrest at G1/S phase were modulated by HIC treatment. MAPK and NF-κB protein array revealed the increased expression of ERK1/2, JNK1/2, p53 phosphorylation, and p53 protein. ERK1/2 and JNK1/2 activations are known to increase the stabilization of p53, a tumor suppressor protein, which is required to arrest the cell cycle at G1/S phase and cause cell death of PCa cells. Overall, our results suggest that HIC can serve as a multi-dimensional chemotherapeutic agent possessing strong cytotoxic, anti-cancer, and anti-metastasis against PCa growth.

Keywords: prostate cancer, P2Y1 receptor, apoptosis, metastasis

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Authors: Restuning Widiasih, Katherine Nelson, Joan Skinner

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Muslim husbands have significant roles in the family including their roles in women’s health and illness. However, studies that explore Muslim husbands’ participation in women’s health is limited. The objective of this study was to uncover Muslim husbands’ participation in women’ health and illness including cancer prevention and screening. A descriptive exploratory approach was used involving 20 Muslim women from urban and rural areas of West Java Province, Indonesia. Muslim women shared experience related to their husbands support and activities in women’s health and illness. The data from the interviews were analyzed using the Comparative Analysis for Interview (CAI). Women perceived that husbands fully supported their health by providing opportunities for activities, and reminding them about healthy food, their workloads, and family planning. Husbands actively involved when women faced health issues including sharing knowledge and experience, discussing any health problems, advising for medical check-ups, and accompanying them for treatments. The analysis also found that husbands were less active and offered less advice regarding prevention and early detection of cancer. This study highlights the significant involvement of Muslim husbands in women’s health and illness, yet a lack of support from husbands related to screening and cancer prevention. This condition could be a burden for Muslim women to participate in health programs related to cancer prevention and early detection. Health education programs to improve Muslim husbands’ understanding of women’s health is needed.

Keywords: descriptive exploratory study, Muslim husbands, Muslim women, women's health and illness

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Authors: F. J. Puertas, M. Castro, A. Tebar, P. J. Fito, R. Gadea, J. M. Monzó, R. J. Colom

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There is a great diversity of diseases that affect the integrity of the walls of the esophagus, generally of a digestive nature. Among them, gastroesophageal reflux is a common disease in the general population, affecting the patient's quality of life; however, there are still unmet diagnostic and therapeutic issues. The consequences of untreated or asymptomatic acid reflux on the esophageal mucosa are not only pain, heartburn, and acid regurgitation but also an increased risk of esophageal cancer. Currently, the diagnostic methods to detect problems in the esophageal tract are invasive and annoying, as 24-hour impedance-pH monitoring forces the patient to be uncomfortable for hours to be able to make a correct diagnosis. In this work, the development of a sensor able to measure in depth is proposed, allowing the detection of liquids circulating in the esophageal tract. The multisensor detection system is based on radiofrequency photospectrometry. At an experimental level, consumers representative of the population in terms of sex and age have been used, placing the sensors between the trachea and the diaphragm analyzing the measurements in vacuum, water, orange juice and saline medium. The results obtained have allowed us to detect the appearance of different liquid media in the esophagus, segregating them based on their ionic content.

Keywords: bioimpedance, dielectric spectroscopy, gastroesophageal reflux, GERD

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Authors: Pavel Damborsky, Martina Zamorova, Jaroslav Katrlik

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Prostate cancer is annually the most common newly diagnosed cancer among men. An extensive number of evidence suggests that traditional serum Prostate-specific antigen (PSA) assay still suffers from a lack of sufficient specificity and sensitivity resulting in vast over-diagnosis and overtreatment. Thus, the early-stage detection of prostate cancer (PCa) plays undisputedly a critical role for successful treatment and improved quality of life. Over the last decade, particular altered glycans have been described that are associated with a range of chronic diseases, including cancer and inflammation. These glycans differences enable a distinction to be made between physiological and pathological state and suggest a valuable biosensing tool for diagnosis and follow-up purposes. Aberrant glycosylation is one of the major characteristics of disease progression. Consequently, the aim of this study was to develop a more reliable tool for early-stage PCa diagnosis employing lectins as glyco-recognition elements. Biosensor and biochip technology putting to use lectin-based glyco-profiling is one of the most promising strategies aimed at providing fast and efficient analysis of glycoproteins. The proof-of-concept experiments based on sandwich assay employing anti-PSA antibody and an aptamer as a capture molecules followed by lectin glycoprofiling were performed. We present a lectin-based biosensing assay for glycoprofiling of serum biomarker PSA using different biosensor and biochip platforms such as label-free surface plasmon resonance (SPR) and microarray with fluorescent label. The results suggest significant differences in interaction of particular lectins with PSA. The antibody-based assay is frequently associated with the sensitivity, reproducibility, and cross-reactivity issues. Aptamers provide remarkable advantages over antibodies due to the nucleic acid origin, stability and no glycosylation. All these data are further step for construction of highly selective, sensitive and reliable sensors for early-stage diagnosis. The experimental set-up also holds promise for the development of comparable assays with other glycosylated disease biomarkers.

Keywords: biomarker, glycosylation, lectin, prostate cancer

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Authors: Makkhan Lal Meena, R. C. Bairwa, G. S. Dangayach, Rahul Jain

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The current study looked at the frequency of chronic illness conditions, accidents, health complaints, and ergonomic issues among 100 conventional and 100 greenhouse farmers. Data related to the health symptoms and ergonomic problems were collected through questionnaires by conducting direct interviews of farmers. According to the findings, symptoms of heat exposure (skin rashes, headache, dizziness, and lack of appetite) were substantially higher among conventional farmers than greenhouse farmers. The greenhouse farmers reported much more pain, numbness, or weakness in wrists/hands, fingers, upper back, hips, and ankles/feet than conventional farmers. The findings of the study suggest that suitable ergonomic knowledge and awareness campaign programs concentrating on safety at work, particularly low back pain, should be implemented in workplaces to allow for earlier detection of symptoms among the greenhouse farmers.

Keywords: accident, conventional farmer, ergonomics, health symptoms, greenhouse farmers, pesticide

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Authors: Vahid Mazloum, Mansour Sahebozamani, Amirhossein Barati, Nouzar Nakhaee, Pouya Rabiei

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Non-specific chronic low back pain (NSCLBP) is a common condition with no exact diagnosis and mechanism for its occurrence. Recently, different therapeutic exercises have taken into account to manage NSCLBP. So, the aim of this study has mainly been placed on comparing the effects of Pilates and Mackenzie exercises on quality of life (QOL) lumbar spine position sense (LSPS) in patients with NSCLBP. In this randomized clinical trial, 47 patients with NSCLBP were voluntarily divided into three groups of Pilates (n=16) (with mean age 37.1 ± 9.5 years, height 168.9 ± 7.4 cm, body mass 76.1 ± 5.9 k), McKenzie (n=15) (with mean age 42.7 ± 8.1 years, height 165.7 ± 6.8, body mass 74.1 ± 4.8 kg) and control (n=16) (with mean age 39.3 ± 9.8 years, height 168.1 ± 8.1 cm, body mass 74.2 ± 5.8 kg). Primary outcome included QOL and secondary was LSPS. Both variables were assessed by the WHOQOL-BREF questionnaires and electrogoniameter, respectively. The measurements were performed at baseline, following a 6-week intervention, and after a 4-week follow-up. The ANCOVA test at P < 0.05 was administrated to analyze the collected data using SPSS software. There was a statistically significant difference between experimental groups and the control group to improve QOL. But, no difference was seen regarding the effects of two exercises on LSPS (p < 0.05). Both Pilates and Mackenzie exercises demonstrated improvement in QOL after 6-week intervention and a 4-week follow-up while none of them considerably affected LSPS. Further studies are required to establish a supporting evidence for the effectiveness of two exercises on NSCLBP.

Keywords: pilates, Mackenzie, preconception, low back pain, physical health

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Authors: Mohammad Kazem Mohammadi

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The use of anticancer agents forms an important part of the treatment of cancer of various types. Uranyl Complexes with DPHMP ligand have been used for the prevention and treatment of cancers. U(IV) metal complexes prepared by reaction of uranyl salt UO2 (NO3)2.6H2O with DPHMP in dry acetonitrile. Characterization of the ligand and its complexes was made by microanalyses, FT-IR, 1H NMR, 13C NMR and UV–Visible spectroscopy. These new complex showed excellent antitumor activity against two kinds of cancer cells that that are HT29:Haman colon adenocarcinoma cell line and T47D:human breast adenocarcinoma cell line.

Keywords: uranyl complexes, DPHMP ligand, antitumor activity, HT29, T47D

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Authors: Harihara Prakash Ramanathan, Daksha Mishra, Ankita Dhaduk

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Relevance: This qualitative study will educate the clinician in putting into practice the advanced method of movement science in restoring the function. Purpose: The purpose of this study is to compare the effectiveness of Active Release Technique and myofascial release technique on range of motion, neck function and pain in patients with upper trapezius spasm. Methods/Analysis: The study was approved by the institutional Human Research and Ethics committee. This study included sixty patients of age group between 20 to 55 years with upper trapezius spasm. Patients were randomly divided into two groups receiving Active Release Technique (Group A) and Myofascial Release Technique (Group B). The patients were treated for 1 week and three outcome measures ROM, pain and functional level were measured using Goniometer, Visual analog scale(VAS), Neck disability Index Questionnaire(NDI) respectively. Paired Sample 't' test was used to compare the differences of pre and post intervention values of Cervical Range of motion, Neck disability Index, Visual analog scale of Group A and Group B. Independent't' test was used to compare the differences between two groups in terms of improvement in cervical range of motion, decrease in visual analogue scale(VAS), decrease in Neck disability index score. Results: Both the groups showed statistically significant improvements in cervical ROM, reduction in pain and in NDI scores. However, mean change in Cervical flexion, cervical extension, right side flexion, left side flexion, right side rotation, left side rotation, pain, neck disability level showed statistically significant improvement (P < 0. 05)) in the patients who received Active Release Technique as compared to Myofascial release technique. Discussion and conclusions: In present study, the average improvement immediately post intervention is significantly greater as compared to before treatment but there is even more improvement after seven sessions as compared to single session. Hence, this proves that several sessions of Manual techniques are necessary to produce clinically relevant results. Active release technique help to reduce the pain threshold by removing adhesion and promote normal tissue extensibility. The act of tensioning and compressing the affected tissue both with digital contact and through the active movement performed by the patient can be a plausible mechanism for tissue healing in this study. This study concluded that both Active Release Technique (ART) and Myofascial release technique (MFR) are equally effective in managing upper trapezius muscle spasm, but more improvement can be achieved by Active Release Technique (ART). Impact and Implications: Active Release Technique can be adopted as mainstay of treatment approach in treating trapezius spasm for faster relief and improving the functional status.

Keywords: trapezius spasm, myofascial release, active release technique, pain

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Authors: Mohammed Al-Zubaidi, Katherine Ong, Pravin Viswambaram, Steve McCombie, Oliver Oey, Jeremy Ong, Richard Gauci, Ronny Low, Dickon Hayne

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Objective: Lymph node involvement along with distant metastasis in a patient with invasive bladder cancer determines the disease survival, therefeor, it is an essential determinant of the therapeutic management and outcome. This retrospective study aims to determine the accuracy of FDG PET scan in detecting lymphatic involvement and distant metastatic urothelial cancer compared to conventional CT staging. Method: A retrospective review of 76 patients with UC or BC who underwent surgery or confirmatory biopsy that was staged with both CT and 18F-FDG-PET (up to 8 weeks apart) between 2015 and 2020. Fifty-sevenpatients (75%) had formal pelvic LN dissection or biopsy of suspicious metastasis. 18F-FDG-PET reports for positive sites were qualitative depending on SUV Max. On the other hand, enlarged LN by RECIST criteria 1.1 (>10 mm) and other qualitative findings suggesting metastasis were considered positive in CT scan. Histopathological findings from surgical specimens or image-guided biopsies were considered the gold standard in comparison to imaging reports. 18F-FDG-avid or enlarged pelvic LNs with surgically proven nodal metastasis were considered true positives. Performance characteristics of 18F-FDG-PET and CT, including sensitivity, specificity, positive predictive value (PPV), and negative predictive value (PPV), were calculated. Results: Pelvic LN involvement was confirmed histologically in 10/57 (17.5%) patients. Sensitivity, specificity, PPV and NPV of CT for detecting pelvic LN metastases were 41.17% (95% CI:18-67%), 100% (95% CI:90-100%) 100% (95% CI:59-100%) and 78.26% (95% CI:64-89%) respectively. Sensitivity, specificity, PPV and NPV of 18F-FDG-PET for detecting pelvic LN metastases were 62.5% (95% CI:35-85%), 83.78% (95% CI:68-94%), 62.5% (95% CI:35-85%), and 83.78% (95% CI:68-94%) respectively. Pre-operative staging with 18F-FDG-PET identified the distant metastatic disease in 9/76 (11.8%) patients who were occult on CT. This retrospective study suggested that 18F-FDG-PET may be more sensitive than CT for detecting pelvic LN metastases. 7/76 (9.2%) patients avoided cystectomy due to 18F-FDG-PET diagnosed metastases that were not reported on CT. Conclusion: 18F-FDG-PET is more sensitive than CT for pelvic LN metastases, which can be used as the standard modality of bladder cancer staging, as it may change the treatment by detecting lymph node metastasis that was occult in CT. Further research involving randomised controlled trials comparing the diagnostic yield of 18F-FDG-PET and CT in detecting nodal and distant metastasis in UC or BC is warranted to confirm our findings.

Keywords: FDG PET, CT scan, urothelial cancer, bladder cancer

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Authors: Isabella Schwartz, Ori Safran, Naama Karniel, Michal Abel, Adina Berko, Martin Seyres, Tamir Tsoar, Sigal Portnoy

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Virtual Reality allows to manipulate the patient’s perception, thereby providing a motivational addition to real-time biofeedback exercises. We aimed to test the effect of manipulated virtual kinematic intervention on measures of active and passive Range of Motion (ROM), pain, and disability level in individuals with traumatic stiff shoulder. In a double-blinded study, patients with stiff shoulder following proximal humerus fracture and non-operative treatment were randomly divided into a non-manipulated feedback group (NM-group; N=6) and a manipulated feedback group (M-group; N=7). The shoulder ROM, pain, and the Disabilities of the Arm, Shoulder and Hand (DASH) scores were tested at baseline and after the 6 sessions, during which the subjects performed shoulder flexion and abduction in front of a graphic visualization of the shoulder angle. The biofeedback provided to the NM-group was the actual shoulder angle and the feedback provided to the M-group was manipulated so that 10° were constantly subtracted from the actual angle detected by the motion capture system. The M-group showed greater improvement in the active flexion ROM, with median and interquartile range of 197.1 (140.5-425.0) compared to 142.5 (139.1-151.3) for the NM-group (p=.046). Also, the M-group showed greater improvement in the DASH scores, with median and interquartile range of 67.7 (52.8-86.2) compared to 89.7 (83.8-98.3) for the NM-group (p=.022). Manipulated intervention is beneficial in individuals with traumatic stiff shoulder and should be further tested for other populations with orthopedic injuries.

Keywords: virtual reality, biofeedback, shoulder pain, range of motion

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Authors: Abdul Kadir, L. Meily Kurniawidjaja

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Batik Madura workers are exposed to many Musculoskeletal Disorders risk factors, particularly Low Back Pain (LBP). This study was conducted as an early detection of ergonomic risk level on Workers Industrial Sentra Batik Madura in Dusun Banyumas, Klampar Subdistrict, Proppo Pamekasan, Madura, East Java. This study includes 12 workers who 11 workers had pain in the upper and lower part of the neck, back, wrist right hand, also 10 workers had pain in the right shoulder. This is a descriptive observational study with cross-sectional approach. Qualitative research by observing workers activity such as draw and putting the wax motif, fabric dyeing, fabric painting, discoloration, washing, and drying. The results are workers have identified ergonomic hazards such as awkward postures, twisting movements, repetitive, and static work postures. Using the method of REBA and QEC, the results get a very high-risk level of activity in each of Madura batik making process is the draw and putting the wax motif, coloring, painting, discoloration, washing, and drying. The level of risk can be reduced by improvement of work equipment include the provision of seats, strut fabric, high settings furnaces, drums, coloring basin, and washing tub.

Keywords: activities of Madura's batik, ergonomic risk level, equipment, QEC (Quick Exposure Checklist), REBA (Rapid Entire Body Assessment)

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Authors: Madiha Liaqat, Rehan Ahmed Khan, Shahid Kamal

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Multiple imputation with delta adjustment is a versatile and transparent technique for addressing univariate missing data in the presence of various missing mechanisms. This approach allows for the exploration of sensitivity to the missing-at-random (MAR) assumption. In this review, we outline the delta-adjustment procedure and illustrate its application for assessing the sensitivity to deviations from the MAR assumption. By examining diverse missingness scenarios and conducting sensitivity analyses, we gain valuable insights into the implications of missing data on our analyses, enhancing the reliability of our study's conclusions. In our study, we focused on assessing logPSA, a continuous biomarker in incomplete prostate cancer data, to examine the robustness of conclusions against plausible departures from the MAR assumption. We introduced several approaches for conducting sensitivity analyses, illustrating their application within the pattern mixture model (PMM) under the delta adjustment framework. This proposed approach effectively handles missing data, particularly loss to follow-up.

Keywords: loss to follow-up, incomplete response, multiple imputation, sensitivity analysis, prostate cancer

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Authors: Dusanee Suwankhong, Pranee Liamputtong

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Breast surgery leaves undesirable scars to all women who experienced mastectomy, despite the fact that this could be a principle approach to save one life. This paper explores how Thai women living with breast cancer perceived and experienced a scarred body after breast surgery. In-depth interviews and drawing methods were employed among 20 women diagnosed with breast cancer. The interviewed data were analysed using thematic analysis method. The results showed that all women with breast cancer who underwent breast surgery perceived and experienced scar as a persisting and visible side-effect. This disfigurement appearance presented a negative image of feminine identity and led to emotional burdens among women. They responded to being scarred in different ways relating to their perceptions of body and changes. The older group had less embarrassed feelings towards being scarred comparing to the younger one. All women tried to seek means to cope with such physical impairment and keep balance life related to their condition. For example, they relied on Buddhism practice and tried to heal the keloid using natural products. Scars appeared to be an unpleasant effect for women who underwent breast mastectomy. Nurses and health care professionals in the local health service sectors need to pay close attention to how the women see the scarred body and their experiences of living with the distorted feminine appearance, and to provide sensitive support that meets the needs of these vulnerable women. The suitable supports can reduce the sense of embarrassment and increase their sense of self-confidence about their social femininity.

Keywords: breast surgery, emotional response, qualitative study, scars, Thai women

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Authors: Nigatu Tadesse, Li Juan, Liuhong Ming

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Gastric cancer (GC) is the fifth most common and fourth deadly cancer in the world with limited treatment options at late advanced stage in which surgical therapy is not recommended with chemotherapy remain as the mainstay of treatment. However, the occurrence of chemoresistance as well as intera-tumoral and inter-tumoral heterogeneity of response to targeted and immunotherapy underlined a clear unmet treatment need in gastroenterology. Several molecular and cellular alterations ascribed for chemo resistance in GC including cancer stem cells (CSC) and tumor microenvironment (TME) remodeling. Cancer cells including CSC bears higher metabolic demand and major changes in TME involves alterations of gut microbiota interacting with nutrients metabolism. Metabolic upregulation in lipids, carbohydrates, amino acids, fatty acids biosynthesis pathways identified as a common hall mark in GC. Metabolic addiction to methionine metabolism occurs in many cancer cells to promote the biosynthesis of S-Adenosylmethionine (SAM), a universal methyl donor molecule for high rate of transmethylation in GC and promote cell proliferation. Targeting methionine metabolism found to promotes chemo-sensitivity with treatment non-heterogeneity. Methionine restriction (MR) promoted the arrest of cell cycle at S/G2 phase and enhanced downregulation of GC cells resistance to apoptosis (including ferroptosis), which suggests the potential of synergy with chemotherapies acting at S-phase of the cell cycle as well as inducing cell apoptosis. Accumulated evidences showed both the biogenesis as well as intracellular metabolism of exogenous methionine could be safe and effective target for therapy either alone or in combination with chemotherapies. This review article provides an over view of the upregulation in methionine biosynthesis pathway and the molecular signaling through the PI3K/Akt/mTOR-c-MYC axis to promote metabolic reprograming through activating the expression of L-type aminoacid-1 (LAT1) transporter and overexpression of Methionine adenosyltransferase 2A(MAT2A) for intercellular metabolic conversion of exogenous methionine to SAM in GC, and the potential of targeting with novel therapeutic agents such as methioninase (METase), Methionine adenosyltransferase 2A (MAT2A), c-MYC, methyl like transferase 16 (METTL16) inhibitors that are currently under clinical trial development stages and future perspectives.

Keywords: gastric cancer, methionine metabolism, pi3k/akt/mtorc1-c-myc axis, gut microbiota, MAT2A, c-MYC, METTL16, methioninase

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