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Fulltext 3D Microfluidic Bone Tumor Microenvironment Comprised of Hydroxyapatite/Fibrin Composite

Ahn J, Lim J, Jusoh N, Lee J, Park TE, Kim Y, et al.

Front Bioeng Biotechnol, 2019;7:168.
PMID: 31380359 DOI: 10.3389/fbioe.2019.00168

Bone is one of the most common sites of cancer metastasis, as its fertile microenvironment attracts tumor cells. The unique mechanical properties of bone extracellular matrix (ECM), mainly composed of hydroxyapatite (HA) affect a number of cellular responses in the tumor microenvironment (TME) such as proliferation, migration, viability, and morphology, as well as angiogenic activity, which is related to bone metastasis. In this study, we engineered a bone-mimetic microenvironment to investigate the interactions between the TME and HA using a microfluidic platform designed for culturing tumor cells in 3D bone-mimetic composite of HA and fibrin. We developed a bone metastasis TME model from colorectal cancer (SW620) and gastric cancer (MKN74) cells, which has very poor prognosis but rarely been investigated. The microfluidic platform enabled straightforward formation of 3D TME composed the hydrogel and multiple cell types. This facilitated monitoring of the effect of HA concentration and culture time on the TME. In 3D bone mimicking culture, we found that HA rich microenvironment affects cell viability, proliferation and cancer cell cytoplasmic volume in a manner dependent on the different metastatic cancer cell types and culture duration indicating the spatial heterogeneity (different origin of metastatic cancer) and temporal heterogeneity (growth time of cancer) of TME. We also found that both SW620 and MKN72 cells exhibited significantly reduced migration at higher HA concentration in our platform indicating inhibitory effect of HA in both cancer cells migration. Next, we quantitatively analyzed angiogenic sprouts induced by paracrine factors that secreted by TME and showed paracrine signals from tumor and stromal cell with a high HA concentration resulted in the formation of fewer sprouts. Finally we reconstituted vascularized TME allowing direct interaction between angiogenic sprouts and tumor-stroma microspheroids in a bone-mimicking microenvironment composing a tunable HA/fibrin composite. Our multifarious approach could be applied to drug screening and mechanistic studies of the metastasis, growth, and progression of bone tumors.

Matched MeSH terms: Bone Neoplasms
Fulltext Aural Polyp or Temporal Bone Carcinoma: Lesson to Learn

Mahmud KA, Nasseri Z, Mohamed Mukari SA, Ismail F, Abdullah A

Cureus, 2021 Mar 01;13(3):e13629.
PMID: 33816028 DOI: 10.7759/cureus.13629

Temporal bone carcinoma is a rare malignant tumor of the head and neck region. Its clinical presentations can mimic benign ear diseases, leading to inaccurate diagnosis and substandard management. We present the case of a 53-year-old female with a three-month history of progressive right otalgia, otorrhea, and hearing loss. Otoscopic examination revealed a mass occupying the right external auditory canal. However, the lesion was presumed to be an aural polyp by several clinicians previously. Multiple courses of oral antibiotics had been prescribed before she was referred to our clinic for the non-resolving aural polyp. Imaging studies showed an external auditory canal soft tissue mass with extradural and parotid extension. The mass was biopsied, and the result was reported as squamous cell carcinoma of the temporal bone. The patient was advised for a total temporal bone resection and parotidectomy; however, she declined the surgical intervention. Within a month, the tumor had metastasized to her lung, liver, and vertebral bodies. She was referred to the Oncology team for palliative chemo-radiotherapy. Temporal bone malignancy must be considered as a differential diagnosis in a middle-aged or elderly patient with a non-resolving aural polyp without a chronic discharging ear. Imaging studies and histopathological evaluation should be prompted to ascertain the diagnosis. Repeated course of oral antibiotic will delay treatment and subsequently may lead to poor prognosis.

Matched MeSH terms: Bone Neoplasms
Fulltext Reconstruction with Composite Cement-Autoclaved Autograft after a Near-Total Excision of the Humerus for Osteosarcoma: A Case Report

Pan, K.L., Zolqarnain A., Ong, G.B.

Malays Orthop J, 2009;3(2):55-57.
MyJurnal

Osteosarcoma occurring in the humerus is often confined to the proximal part, in which case, reconstruction after excision is less daunting. When the tumour spreads down the medullary cavity distally, a total humeral replacement is often required. This is costly and beyond the means of the average patient in a developing country. An amputation is often the procedure of first resort. We report a 13-year-old boy with osteosarcoma originating from the left proximal humerus, with involvement of the marrow reaching down to the distal diaphyseal-metaphyseal junction, leaving only 6 cm of the distal humerus intact after wide resection. Reconstruction of the defect was done with a composite cement-autoclaved autograft fixed to the remaining humerus with a plate. At 40 months of follow-up, the patient is well with normal function of the elbow, wrist and hand. Salvaging the limb despite near total involvement of the humerus by high grade osteosarcoma is possible using material available in the average orthopaedic operating room.

Matched MeSH terms: Bone Neoplasms
Fulltext Brodie's Abscess of Posterior Ilium with Gluteal Syndrome, an Unusual Cause of Paediatric Low Back Pain: A Case Report

Behera G, Poduval M, Patro DK, Sahoo S

Malays Orthop J, 2017 Jul;11(2):68-71.
PMID: 29021883 DOI: 10.5704/MOJ.1707.009

Brodie's abscess is a variety of subacute osteomyelitis with a long duration of presentation and intermittent pain. It usually involves the metaphyseal region of long bones of the lower limbs. Brodie's abscess of pelvic bone is very rare. Involvement of posterior ilium with gluteal syndrome is extremely unusual and can be easily missed or misdiagnosed. We present a 9-year old boy who reported to us with intermittent low back pain of three months duration without any other constitutional symptoms. Clinically, there was mild tenderness over the posterior ilium. Computed tomography showed a lytic lesion in the posterior ilium with a breach in the outer cortex. MRI and bone scan were suggestive of inflammatory pathology. Keeping infective, tubercular and benign bone tumors as differential diagnoses, open biopsy and curettage were done. Staphylococcus aureus was cultured and histopathology was suggestive of osteomyelitis. The patient received appropriate antibiotics for six weeks. He was asymptomatic till 18 months of follow up without any recurrence. We present this case because of its rarity and unusual presentation as gluteal syndrome and low back pain, and its resemblance to other pelvic and sacroiliac joint pathologies which are often missed or misdiagnosed in paediatric patients.

Study done in India

Matched MeSH terms: Bone Neoplasms
Fulltext Metastatic Bone Disease Secondary to Bronchial Adenocarcinoma in a Patient with Paget's Disease of the Bone

Lim KP, Kok WH, Kamaruddin NA

J ASEAN Fed Endocr Soc, 2018;33(1):63-68.
PMID: 33442113 DOI: 10.15605/jafes.033.01.11

A 69-year-old female complained of intermittent left hip pain for the past 3 years. Biochemical tests revealed normal serum calcium and phosphorus with markedly raised alkaline phosphatase. MRI of the hip revealed extensive marrow signal abnormalities at the left pelvic bone, while CT of the thorax revealed a spiculated lung nodule at the left lower lung lobe. In order to diagnose either primary, metastatic bone tumour or Paget's disease of the bone (PDB), an open biopsy of the left iliac bone was performed. The histopathology of bone biopsy of the left iliac bone was consistent with PDB. A CT guided biopsy of the lung mass done later revealed adenocarcinoma of the lung. She had 18F-FDG PETCECT Scan for staging evaluation and result was suggestive of new bony metastases. Patient was started on IV Zoledronic acid for treatment of the PDB. In view of the stage 4 lung adenocarcinoma with bony metastases, patient was scheduled for palliative chemotherapy.

Matched MeSH terms: Bone Neoplasms
Fulltext Avoiding diagnostic pitfalls in mimics of neoplasia: the importance of a comprehensive diagnostic approach

Samsudin EZ, Kamarul T, Mansor A

Singapore Med J, 2015 May;56(5):e92-5.
PMID: 26034328 DOI: 10.11622/smedj.2015082

Any medical diagnosis should take a multimodal approach, especially those involving tumour-like conditions, as entities that mimic neoplasms have overlapping features and may present detrimental outcomes if they are underdiagnosed. These case reports present diagnostic pitfalls resulting from overdependence on a single diagnostic parameter for three musculoskeletal neoplasm mimics: brown tumour (BT) that was mistaken for giant cell tumour (GCT), methicillin-resistant Staphylococcus aureus osteomyelitis mistaken for osteosarcoma and a pseudoaneurysm mistaken for a soft tissue sarcoma. Literature reviews revealed five reports of BT simulating GCT, four reports of osteomyelitis mimicking osteosarcoma and five reports of a pseudoaneurysm imitating a soft tissue sarcoma. Our findings highlight the therapeutic dilemmas that arise with musculoskeletal mimics, as well as the importance of thorough investigation to distinguish mimickers from true neoplasms.

Matched MeSH terms: Bone Neoplasms/diagnosis
Fulltext In vitro delivery and controlled release of Doxorubicin for targeting osteosarcoma bone cancer

Kamba SA, Ismail M, Hussein-Al-Ali SH, Ibrahim TA, Zakaria ZA

Molecules, 2013 Aug 30;18(9):10580-98.
PMID: 23999729 DOI: 10.3390/molecules180910580

Drug delivery systems are designed to achieve drug therapeutic index and enhance the efficacy of controlled drug release targeting with specificity and selectivity by successful delivery of therapeutic agents at the desired sites without affecting the non-diseased neighbouring cells or tissues. In this research, we developed and demonstrated a bio-based calcium carbonate nanocrystals carrier that can be loaded with anticancer drug and selectively deliver it to cancer cells with high specificity by achieving the effective osteosarcoma cancer cell death without inducing specific toxicity. The results showed pH sensitivity of the controlled release characteristics of the drug at normal physiological pH 7.4 with approximately 80% released within 1,200 min but when exposed pH 4.8 the corresponding 80% was released in 50 min. This study showed that the DOX-loaded CaCO₃ nanocrystals have promising applications in delivery of anticancer drugs.

Matched MeSH terms: Bone Neoplasms/drug therapy*
Impact of chemotherapy on hypercalcemia in breast and lung cancer patients

Hassan BA, Yusoff ZB, Hassali MA, Othman SB, Weiderpass E

Asian Pac J Cancer Prev, 2012;13(9):4373-8.
PMID: 23167346

INTRODUCTION: Hypercalcemia is mainly caused by bone resorption due to either secretion of cytokines including parathyroid hormone-related protein (PTHrP) or bone metastases. However, hypercalcemia may occur in patients with or without bone metastases. The present study aimed to describe the effect of chemotherapy treatment, regimens and doses on calcium levels among breast and lung cancer patients with hypercalcemia.
METHODS: We carried a review of medical records of breast and lung cancer patients hospitalized in years 2003 and 2009 at Penang General Hospital, a public tertiary care center in Penang Island, north of Malaysia. Patients with hypercalcemia (defined as a calcium level above 10.5 mg/dl) at the time of cancer diagnosis or during cancer treatment had their medical history abstracted, including presence of metastasis, chemotherapy types and doses, calcium levels throughout cancer treatment, and other co-morbidity. The mean calcium levels at first hospitalization before chemotherapy were compared with calcium levels at the end of or at the latest chemotherapy treatment. Statistical analysis was conducted using the Chi-square test for categorical data, logistic regression test for categorical variables, and Spearman correlation test, linear regression and the paired sample t tests for continuous data.
RESULTS: Of a total 1,023 of breast cancer and 814 lung cancer patients identified, 292 had hypercalcemia at first hospitalization or during cancer treatment (174 breast and 118 lung cancer patients). About a quarter of these patients had advanced stage cancers: 26.4% had mild hypercalcemia (10.5-11.9 mg/dl), 55.5% had moderate (12-12.9 mg/dl), and 18.2% severe hypercalcemia (13-13.9; 14-16 mg/dl). Chemotherapy lowered calcium levels significantly both in breast and lung cancer patients with hypercalcemia; in particular with chemotherapy type 5-flurouracil+epirubicin+cyclophosphamide (FEC) for breast cancer, and gemcitabine+cisplatin in lung cancer.
CONCLUSION: Chemotherapy decreases calcium levels in breast and lung cancer cases with hypercalcemia at cancer diagnosis, probably by reducing PTHrP levels.

Matched MeSH terms: Bone Neoplasms/blood*; Bone Neoplasms/secondary